The U.S. Food and Drug Administration approved Actemra (tocilizumab) on Friday to treat adults with moderate to severe rheumatoid arthritis who have not adequately responded to or cannot tolerate other approved drug classes for rheumatoid arthritis.
Actemra recommended use is limited to patients who have failed other approved therapies because of serious safety concerns that were noted in clinical studies. These safety concerns include elevated liver enzymes, elevated Low-density lipoprotein (LDL) or bad cholesterol, hypertension, and gastrointestinal perforations.
"Physicians and patients need to be aware of the risk of serious adverse effects of Actemra and make informed decisions regarding its benefits and risks in the treatment of individual patients," said Bob Rappaport, M.D., director of the Division of Analgesics, Anesthetics and Rheumatology Products in the FDA's Center for Drug Evaluation and Research.
The FDA is requiring the sponsor to conduct a post-marketing clinical trial to further evaluate the long-term safety of Actemra. Specifically, the FDA wants to evaluate the impact of elevated LDL cholesterol and blood pressure seen in some patients in shorter-term trials on the cardiovascular health of patients treated with Actemra.
In addition, a Risk Evaluation and Mitigation Strategy (REMS) will require the drug sponsor to implement a Communication Plan for physicians informing them how to appropriately monitor their patients for liver and/or gastrointestinal side effects. The REMS will include a Medication Guide to ensure that patients are informed of the benefits and risks of Actemra.
Actemra works by blocking the action of interleukin-6, an immune system protein that is overabundant in people with rheumatoid arthritis.
The effectiveness and safety of Actemra was determined in five clinical trials in adult patients with active rheumatoid arthritis. In all of the trials, patients treated with Actemra experienced greater improvement in their tender or swollen joints than patients treated with a placebo.
The most common adverse reactions in clinical trials were upper respiratory tract infections, headache, inflammation of the nose or nasal passage, high blood pressure and increased liver enzymes. Elevations in the LDL or bad cholesterol were also seen in some patients, some of whom required the addition of lipid lowering agents.
Patients treated with Actemra are at increased risk for developing serious infections. Most patients who developed these infections in clinical trials were also taking other drugs that suppress the immune system such as methotrexate or corticosteroids.
Actemra is marketed by San Francisco-based Genentech Inc., a subsidiary of the Roche Group.
Source
U.S. Food and Drug Administration
View drug information on Actemra.
понедельник, 30 мая 2011 г.
Rheumatology Specialist Nurses: ??100 Million "added Value" To NHS Per Year, Wales
Every rheumatology specialist nurse increases efficiency in the NHS by a quarter of a million pounds each year according to new research published by the Royal College of Nursing at its annual Congress in Bournemouth.
By managing the bulk of the outpatient workload, rheumatology specialist nurses free up hundreds of appointments for new patients to be seen by a consultant - this represents a saving of ??175,168 per nurse each year through increased efficiency. Additionally, as a result of the telephone support specialist nurses provide, many GP appointments can be freed up for other patients, equating to a further ??73,588 saving per nurse.
The UK-wide study - Clinical nurse specialists: adding value to care - monitored the working pattern of rheumatology specialist nurses over a year using a software based modelling tool to determine how their time is spent.
The research published today also found that providing administrative support for rheumatology specialist nurses would free up more than six hours of their working week, meaning they could devote even more time to patient care, resulting in further savings to the NHS.
This latest study adds further weight to the College's recent warning that cutting specialist nurse services for people with long term conditions would be a false economy. The RCN is now calling for the methodology to be rolled out to cover all specialist nurses to identify the true extent of savings that could be made.
Specialist nurse posts save millions of pounds from health budgets through reduced complications, fewer hospital re-admissions and the expert long term management of conditions. They also provide many patients and families with a lifeline which no other service can offer.
In spite of this, a recent RCN survey of 60 leading health organisations representing thousands of people with a long-term condition found that only a third (36%) of respondents felt that everyone who needed specialist nursing currently received it. The survey also found:
- More than a third (37%) of respondents had seen cuts in services over the last 12 months
- More than half (57%) were concerned that posts will be threatened in the near future
- Almost all (95%) of the respondents who had seen cuts in services say it is the NHS, rather than other joint-funders, who have cut or reduced funding for specialist nurses
Tina Donnelly, Director of the Royal College of Nursing in Wales, said: "Specialist Nurses work in a defined area of practice - they may work at advanced levels in a specialist role or simply focus their practice in one particular area. The role is often about patient communication, teaching and support of self management of disease and illness, reviewing medication, and organising the patient pathway and access to other services. Patients with long term conditions frequently identify the specialist nurse as one of the most important healthcare professionals."
"This study looks at the value of specialist nursing in rheumatology; however, we know that similar findings could be found in other areas. Advanced and Specialist Nurses make a difference to patients lives and have a beneficial impact on the health service they work in. The roles bring many benefits to patients including continuity of care, access to expertise, improved clinical outcomes, and an excellent relationship between patient and healthcare professional. Another area of benefit is the accessibility and completeness of the services provided."
In its election manifesto, the RCN is calling for every patient with a long-term condition to have guaranteed access to specialist nursing care.
Notes
The study findings will be presented at the RCN Annual Congress 2010 fringe event "Capturing the essence and demonstrating the value of clinical nurse specialists" at 5:45pm on Monday 26th April 2010.
The study used Pandora, a software-based modelling tool, to record the complex activity of clinical specialist nurses working in the field of rheumatology between March 2009 and March 2010. It recorded the work of 99 rheumatology specialist nurses spread across the four countries of the UK.
Specialist nurses are dedicated clinical experts who are able to spend time with patients with a particular condition, and help them with everything from drug treatments to exercise plans, and help to ensure that patients have the highest possible quality of life.
Source
Royal College of Nursing (RCN)
By managing the bulk of the outpatient workload, rheumatology specialist nurses free up hundreds of appointments for new patients to be seen by a consultant - this represents a saving of ??175,168 per nurse each year through increased efficiency. Additionally, as a result of the telephone support specialist nurses provide, many GP appointments can be freed up for other patients, equating to a further ??73,588 saving per nurse.
The UK-wide study - Clinical nurse specialists: adding value to care - monitored the working pattern of rheumatology specialist nurses over a year using a software based modelling tool to determine how their time is spent.
The research published today also found that providing administrative support for rheumatology specialist nurses would free up more than six hours of their working week, meaning they could devote even more time to patient care, resulting in further savings to the NHS.
This latest study adds further weight to the College's recent warning that cutting specialist nurse services for people with long term conditions would be a false economy. The RCN is now calling for the methodology to be rolled out to cover all specialist nurses to identify the true extent of savings that could be made.
Specialist nurse posts save millions of pounds from health budgets through reduced complications, fewer hospital re-admissions and the expert long term management of conditions. They also provide many patients and families with a lifeline which no other service can offer.
In spite of this, a recent RCN survey of 60 leading health organisations representing thousands of people with a long-term condition found that only a third (36%) of respondents felt that everyone who needed specialist nursing currently received it. The survey also found:
- More than a third (37%) of respondents had seen cuts in services over the last 12 months
- More than half (57%) were concerned that posts will be threatened in the near future
- Almost all (95%) of the respondents who had seen cuts in services say it is the NHS, rather than other joint-funders, who have cut or reduced funding for specialist nurses
Tina Donnelly, Director of the Royal College of Nursing in Wales, said: "Specialist Nurses work in a defined area of practice - they may work at advanced levels in a specialist role or simply focus their practice in one particular area. The role is often about patient communication, teaching and support of self management of disease and illness, reviewing medication, and organising the patient pathway and access to other services. Patients with long term conditions frequently identify the specialist nurse as one of the most important healthcare professionals."
"This study looks at the value of specialist nursing in rheumatology; however, we know that similar findings could be found in other areas. Advanced and Specialist Nurses make a difference to patients lives and have a beneficial impact on the health service they work in. The roles bring many benefits to patients including continuity of care, access to expertise, improved clinical outcomes, and an excellent relationship between patient and healthcare professional. Another area of benefit is the accessibility and completeness of the services provided."
In its election manifesto, the RCN is calling for every patient with a long-term condition to have guaranteed access to specialist nursing care.
Notes
The study findings will be presented at the RCN Annual Congress 2010 fringe event "Capturing the essence and demonstrating the value of clinical nurse specialists" at 5:45pm on Monday 26th April 2010.
The study used Pandora, a software-based modelling tool, to record the complex activity of clinical specialist nurses working in the field of rheumatology between March 2009 and March 2010. It recorded the work of 99 rheumatology specialist nurses spread across the four countries of the UK.
Specialist nurses are dedicated clinical experts who are able to spend time with patients with a particular condition, and help them with everything from drug treatments to exercise plans, and help to ensure that patients have the highest possible quality of life.
Source
Royal College of Nursing (RCN)
Method To Dampen Immune Response Holds Promise For Treatment Of Cancer, Autoimmune Diseases, Transplant Rejection
National Jewish Health has been issued a US patent claiming a method to desensitize B cells by inactivating antigen receptors on their surfaces. The method, discovered by John Cambier, PhD, Chairman of the Integrated Department of Immunology at National Jewish Health, holds promise for treatment of B-cell mediated diseases, such as lymphoma and leukemia, rheumatoid arthritis, lupus and rejection of organ transplants. This therapeutic approach has the potential advantage of inactivating B cells instead of killing them as current treatments do. Therefore, this potential therapy could be more rapidly adjusted in response to the changing needs of patients.
B cells are a crucial part of the adaptive immune response, responsible for making antibodies that can neutralize and destroy pathogens. Several diseases, however, are associated with malfunction of B cells. For example, B cells can turn cancerous in diseases such as lymphoma and leukemia. In autoimmune diseases, such as rheumatoid arthritis or lupus, B cells turn against their own bodies and attack their tissues. B cells can also attack transplanted organs, which they recognize as foreign and potentially harmful.
The recently issued patent describes a method to inactivate B cells by disassembling their B-cell receptors. B cells begin producing antibodies after their B-cell receptors encounter foreign protein fragments, known as antigens. The B-cell receptor contains two distinct subunits; a receptor, which engages antigens, and a transducer, which transmits an activating signal to the interior of the cell.
About a decade ago, Dr. Cambier's laboratory, discovered that the two subunits could be separated, which disables the B cell's ability to recognize antigens and produce antibodies. In 2003, National Jewish Health received a patent (#6,503,509) for this method of B -cell desensitization. The most recent patent (#7,825,224) related to this technology claims the use of antibodies that bind to the transducer subunit of the receptor to inactivate the B cell.
Dr. Cambier's laboratory has recently developed several antibodies against one of the transducer elements, CD79, that have already yielded promising results.
"In contrast to current therapies for B-cell diseases, this method does not kill B cells, it merely inactivates them," said Dr. Cambier. "That could potentially allow for greater flexibility in using a therapy that is developed with this technology. Instead of the months to years it sometimes takes for the effects of current therapy to wane, our method could be reversed within days."
Dr. Cambier has recently received research funding from the State of Colorado and National Jewish Health through the Bioscience Discovery Evaluation Grant Program to further develop this promising technology.
"This research funding underlines our commitment to promote the translation of our scientists' research findings into therapeutic or diagnostic products that can ultimately help patients worldwide," said Emmanuel Hilaire, PhD, Manager of the Technology Transfer Office at National Jewish Health. "National Jewish is currently exploring various commercialization venues for its licensing, including the creation of a start-up company in Colorado."
Source:
William Allstetterx
National Jewish Health
B cells are a crucial part of the adaptive immune response, responsible for making antibodies that can neutralize and destroy pathogens. Several diseases, however, are associated with malfunction of B cells. For example, B cells can turn cancerous in diseases such as lymphoma and leukemia. In autoimmune diseases, such as rheumatoid arthritis or lupus, B cells turn against their own bodies and attack their tissues. B cells can also attack transplanted organs, which they recognize as foreign and potentially harmful.
The recently issued patent describes a method to inactivate B cells by disassembling their B-cell receptors. B cells begin producing antibodies after their B-cell receptors encounter foreign protein fragments, known as antigens. The B-cell receptor contains two distinct subunits; a receptor, which engages antigens, and a transducer, which transmits an activating signal to the interior of the cell.
About a decade ago, Dr. Cambier's laboratory, discovered that the two subunits could be separated, which disables the B cell's ability to recognize antigens and produce antibodies. In 2003, National Jewish Health received a patent (#6,503,509) for this method of B -cell desensitization. The most recent patent (#7,825,224) related to this technology claims the use of antibodies that bind to the transducer subunit of the receptor to inactivate the B cell.
Dr. Cambier's laboratory has recently developed several antibodies against one of the transducer elements, CD79, that have already yielded promising results.
"In contrast to current therapies for B-cell diseases, this method does not kill B cells, it merely inactivates them," said Dr. Cambier. "That could potentially allow for greater flexibility in using a therapy that is developed with this technology. Instead of the months to years it sometimes takes for the effects of current therapy to wane, our method could be reversed within days."
Dr. Cambier has recently received research funding from the State of Colorado and National Jewish Health through the Bioscience Discovery Evaluation Grant Program to further develop this promising technology.
"This research funding underlines our commitment to promote the translation of our scientists' research findings into therapeutic or diagnostic products that can ultimately help patients worldwide," said Emmanuel Hilaire, PhD, Manager of the Technology Transfer Office at National Jewish Health. "National Jewish is currently exploring various commercialization venues for its licensing, including the creation of a start-up company in Colorado."
Source:
William Allstetterx
National Jewish Health
Recent Findings Suggest Need For New Approach To Fighting Disease, Says Dr. Jon J. Kabara
Microorganisms may be the origin behind many diseases when certain circumstances are present, according to new research findings, and often without noticeable infection. Experts believe pathogenic viruses, bacteria, yeasts, and fungi can cause clinical inflammatory problems resulting from low-grade infections that may go unnoticed. These new findings, according to Dr. Jon J. Kabara, require a whole new approach to disease chemotherapy. Med-Chem Labs Inc. is using an approach that eliminates the cause (microorganisms) while relieving the effect (inflammation). A naturally derived food nutrient from mother's milk is currently under investigation to promote health and well being.
The following diseases and conditions have a possible inflammatory component:
- Cardiovascular events
- Atherosclerosis
- Inflammatory bowel disease (Crohn's disease, ulcerative colitis)
- Fibromyalgia
- Psoriasis
- Rheumatoid arthritis
The more scientists learn about these and other serious diseases, the more pathologies are being linked with the long-term effects of infection/inflammation in the body. The inflammation-disease connection has become a hot research topic that is expected to explode soon. The therapeutic approach by Med-Chem Labs Inc. is to work with health professionals using a natural fat found in mother's milk that has multiple functional properties (anti-inflammatory/ antimicrobial/immune booster agents). The use of a food grade nutrient is to promote health and self-healing rather than drug treatment.
While confirmation of this hypothesis is currently being investigated in the United States, dermatology studies are now being conducted in the Philippines. Said Obama, the United States President's uncle, has also started research on HIV in Kenya using this food grade nutrient.
Dr. Kabara was the first to pursue the unique health benefits of Lauricidin®, which has now been extensively tested in university, government (CDC), and medical laboratories. As a result, his initial findings have been confirmed by many and reported in peer reviewed scientific journals, books, and patents. Through advanced technology, this natural substance is now available from Med-Chem Laboratories in 95% pure pearlized form.
Source
Med-Chem Laboratories Inc.
The following diseases and conditions have a possible inflammatory component:
- Cardiovascular events
- Atherosclerosis
- Inflammatory bowel disease (Crohn's disease, ulcerative colitis)
- Fibromyalgia
- Psoriasis
- Rheumatoid arthritis
The more scientists learn about these and other serious diseases, the more pathologies are being linked with the long-term effects of infection/inflammation in the body. The inflammation-disease connection has become a hot research topic that is expected to explode soon. The therapeutic approach by Med-Chem Labs Inc. is to work with health professionals using a natural fat found in mother's milk that has multiple functional properties (anti-inflammatory/ antimicrobial/immune booster agents). The use of a food grade nutrient is to promote health and self-healing rather than drug treatment.
While confirmation of this hypothesis is currently being investigated in the United States, dermatology studies are now being conducted in the Philippines. Said Obama, the United States President's uncle, has also started research on HIV in Kenya using this food grade nutrient.
Dr. Kabara was the first to pursue the unique health benefits of Lauricidin®, which has now been extensively tested in university, government (CDC), and medical laboratories. As a result, his initial findings have been confirmed by many and reported in peer reviewed scientific journals, books, and patents. Through advanced technology, this natural substance is now available from Med-Chem Laboratories in 95% pure pearlized form.
Source
Med-Chem Laboratories Inc.
Old Antibiotic May Find New Life As A Stroke Treatment
An old intravenous antibiotic may have new life as a stroke treatment, researchers say.
Minocycline appears to reduce stroke damage in multiple ways - inhibiting white blood cells and enzymes that, at least acutely, can destroy brain tissue and blood vessels, respectively, says Dr. David Hess, chair of the Department of Neurology in the Medical College of Georgia School of Medicine. The broad-spectrum antibiotic also seems to reduce cell suicide in the minutes and hours following a stroke, enabling more cells to recover.
He and other researchers leading a clinical trial that will study the drug in 60 stroke patients in Georgia, Kentucky and Oregon say they believe the antibiotic will be a safe, effective adjunct therapy for tPA, the only FDA-approved drug therapy for strokes.
"It's a safe drug that is easy to give and tolerate, that gets into the brain well, and may reduce bleeding, the primary side effect of tPA," says Dr. Hess, principal investigator on the $1.8 million National Institute of Neurological Disorders and Stroke-funded clinical trial. "We think it will make strokes smaller and patient outcomes better."
Their animal studies have shown the drug, given within six hours of a stroke, then every 12 hours for up to three days - the peak time of inflammation - reduces stroke damage by up to 40 percent.
"We know it's safe in humans and we know the concentrations we need to see improvement in the brains of rats can be achieved safely in humans," says Dr. Susan C. Fagan, professor of pharmacy at the University of Georgia, assistant dean for the MCG program of the UGA College of Pharmacy and study co-investigator. "That's an important consideration."
The drug's safety and optimal stroke dose are the primary focus of the phase-one clinical trial in stroke patients who arrive at MCG, University of Kentucky or Oregon Health & Science University within six hours of symptom onset and with measurable neurological symptoms. Every study patient will get one of four doses, starting with 200 milligrams, the most common dose already used, and increasing incrementally up to 700 milligrams. They'll get half their first dose at subsequent 12-hour intervals for a three-day period then be followed for 90 days.
"We are going to be drawing samples from patients to make sure we achieve the concentrations that we want in the blood, plus we want to define the half-life in stroke patients to see if it's different than in the younger patients who take it for other reasons,' says Dr. Fagan. Newer intravenous antibiotics have replaced minocycline in the United States, but an oral version is used to treat conditions such as acne and rheumatoid arthritis. "If the half-life is longer, we can give it less frequently. We are really fine-tuning the dose," she says. They'll do this by looking in the blood for biomarkers, indicators of inflammation, to see if inflammatory factors go up after three days. "It may give us a clue we should treat patients longer," says Dr. Fagan, a co-investigator on the studies leading to minocycline's use in rheumatoid arthritis.
One way minocycline fights inflammation is by inhibiting microglial cells, white blood cells activated by a stroke, says Dr. Hess. "When they get activated, they get angry and produce materials that damage the brain. The inflammatory cascade is bad and good. Early on it's bad, later on it may actually do some good things," he says. Typically these microglial cells are sentinel immune cells for the brain, helping eliminate infections and secreting factors that support neurons. However, acutely in a stroke, brain tissue can become their target. "They are basically cleaning house at first, then later, they are supportive, releasing growth factors and promoting the growth of new blood vessels," adds Dr. Fagan.
Minocycline also blocks matrix metallo-proteinases, also released during stroke, which destroy the basement membrane of blood vessels. The presence of these enzymes also is a mixed bag. "If you want angiogenesis - you want to make new blood vessels - you need MMPs around to get rid of the old ones, like tearing down an old building to build a new one," says Dr. Hess. However, in patients lucky enough to get the clot buster tPA, the enzyme increases the major risk factor: bleeding. Dr. Hess notes that while this initial clinical trial is in ischemic strokes, he thinks minocycline also may be useful in hemorrhagic strokes, which account for about 12 percent of strokes, where clearly blocking MMPs would come in handy.
Minocycline also works by blocking apoptosis, or cell suicide, an observation originally made by MCG Cell Biologist Zheng Dong. "It does this by increasing a protein called bcl-2, which helps cells survive," says Dr. Hess.
The antibiotic's potential usefulness in protecting brain cells began surfacing in scientific literature within the last few years. "It was so interesting to us because we knew that a lot of the limitations of other drugs that had been tried in rodents but didn't work in stroke patients were that they didn't cross into the brain," Dr. Fagan says. "We knew that minocycline did based on previous experiments and the fact that many people who take it for acne or rheumatoid arthritis get dizzy. So we were encouraged by this.
"We wanted something we could give at least three hours after stroke or later. In our studies in animal models, we found at delayed time intervals it was profoundly neuroprotective," says Dr. Fagan. "We studied it at multiple time points at multiple doses and, in fact, some of the most important work we did was finding out how the rodent dose really could be translated to humans," she says, referencing work published in Experimental Neurology in 2004.
For the clinical trial, Wyeth Pharmaceuticals will make the sterile powder used for injection available from Japan, where it's still in use.
At MCG, Dr. Hess as well as MCG Neurologists Chris Hall, Fenwick Nichols and Jeff Switzer are enrolling patients in the study. Other MCG contributors include Biostatistician Jennifer Waller and Physiologist Adviye Ergul.
Source: Toni Baker
Medical College of Georgia
Minocycline appears to reduce stroke damage in multiple ways - inhibiting white blood cells and enzymes that, at least acutely, can destroy brain tissue and blood vessels, respectively, says Dr. David Hess, chair of the Department of Neurology in the Medical College of Georgia School of Medicine. The broad-spectrum antibiotic also seems to reduce cell suicide in the minutes and hours following a stroke, enabling more cells to recover.
He and other researchers leading a clinical trial that will study the drug in 60 stroke patients in Georgia, Kentucky and Oregon say they believe the antibiotic will be a safe, effective adjunct therapy for tPA, the only FDA-approved drug therapy for strokes.
"It's a safe drug that is easy to give and tolerate, that gets into the brain well, and may reduce bleeding, the primary side effect of tPA," says Dr. Hess, principal investigator on the $1.8 million National Institute of Neurological Disorders and Stroke-funded clinical trial. "We think it will make strokes smaller and patient outcomes better."
Their animal studies have shown the drug, given within six hours of a stroke, then every 12 hours for up to three days - the peak time of inflammation - reduces stroke damage by up to 40 percent.
"We know it's safe in humans and we know the concentrations we need to see improvement in the brains of rats can be achieved safely in humans," says Dr. Susan C. Fagan, professor of pharmacy at the University of Georgia, assistant dean for the MCG program of the UGA College of Pharmacy and study co-investigator. "That's an important consideration."
The drug's safety and optimal stroke dose are the primary focus of the phase-one clinical trial in stroke patients who arrive at MCG, University of Kentucky or Oregon Health & Science University within six hours of symptom onset and with measurable neurological symptoms. Every study patient will get one of four doses, starting with 200 milligrams, the most common dose already used, and increasing incrementally up to 700 milligrams. They'll get half their first dose at subsequent 12-hour intervals for a three-day period then be followed for 90 days.
"We are going to be drawing samples from patients to make sure we achieve the concentrations that we want in the blood, plus we want to define the half-life in stroke patients to see if it's different than in the younger patients who take it for other reasons,' says Dr. Fagan. Newer intravenous antibiotics have replaced minocycline in the United States, but an oral version is used to treat conditions such as acne and rheumatoid arthritis. "If the half-life is longer, we can give it less frequently. We are really fine-tuning the dose," she says. They'll do this by looking in the blood for biomarkers, indicators of inflammation, to see if inflammatory factors go up after three days. "It may give us a clue we should treat patients longer," says Dr. Fagan, a co-investigator on the studies leading to minocycline's use in rheumatoid arthritis.
One way minocycline fights inflammation is by inhibiting microglial cells, white blood cells activated by a stroke, says Dr. Hess. "When they get activated, they get angry and produce materials that damage the brain. The inflammatory cascade is bad and good. Early on it's bad, later on it may actually do some good things," he says. Typically these microglial cells are sentinel immune cells for the brain, helping eliminate infections and secreting factors that support neurons. However, acutely in a stroke, brain tissue can become their target. "They are basically cleaning house at first, then later, they are supportive, releasing growth factors and promoting the growth of new blood vessels," adds Dr. Fagan.
Minocycline also blocks matrix metallo-proteinases, also released during stroke, which destroy the basement membrane of blood vessels. The presence of these enzymes also is a mixed bag. "If you want angiogenesis - you want to make new blood vessels - you need MMPs around to get rid of the old ones, like tearing down an old building to build a new one," says Dr. Hess. However, in patients lucky enough to get the clot buster tPA, the enzyme increases the major risk factor: bleeding. Dr. Hess notes that while this initial clinical trial is in ischemic strokes, he thinks minocycline also may be useful in hemorrhagic strokes, which account for about 12 percent of strokes, where clearly blocking MMPs would come in handy.
Minocycline also works by blocking apoptosis, or cell suicide, an observation originally made by MCG Cell Biologist Zheng Dong. "It does this by increasing a protein called bcl-2, which helps cells survive," says Dr. Hess.
The antibiotic's potential usefulness in protecting brain cells began surfacing in scientific literature within the last few years. "It was so interesting to us because we knew that a lot of the limitations of other drugs that had been tried in rodents but didn't work in stroke patients were that they didn't cross into the brain," Dr. Fagan says. "We knew that minocycline did based on previous experiments and the fact that many people who take it for acne or rheumatoid arthritis get dizzy. So we were encouraged by this.
"We wanted something we could give at least three hours after stroke or later. In our studies in animal models, we found at delayed time intervals it was profoundly neuroprotective," says Dr. Fagan. "We studied it at multiple time points at multiple doses and, in fact, some of the most important work we did was finding out how the rodent dose really could be translated to humans," she says, referencing work published in Experimental Neurology in 2004.
For the clinical trial, Wyeth Pharmaceuticals will make the sterile powder used for injection available from Japan, where it's still in use.
At MCG, Dr. Hess as well as MCG Neurologists Chris Hall, Fenwick Nichols and Jeff Switzer are enrolling patients in the study. Other MCG contributors include Biostatistician Jennifer Waller and Physiologist Adviye Ergul.
Source: Toni Baker
Medical College of Georgia
Genes That Increase Rheumatoid Arthritis Risk Identified By Researchers
Researchers in the United States and Sweden have identified a genetic region associated with increased risk of rheumatoid arthritis (RA), a chronic and debilitating inflammatory disease of the joints that affects an estimated 2.1 million Americans. The U.S. arm of the study involved a long-time collaboration between intramural researchers of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and other organizations. NIAMS is one of 27 institutes and centers at the National Institutes of Health. The results appeared in the New England Journal of Medicine.
Using the relatively new genome-wide association approach -- which makes it possible to analyze between 300,000 and 500,000 single nucleotide polymorphisms (SNPs, or small differences in DNA that are distributed throughout a person's genetic code) -- researchers in both countries searched for genetic differences in blood samples from people with RA compared to controls. The U.S. group compared 908 samples from patients provided by the North American Rheumatoid Arthritis Consortium (NARAC) -- a group of investigators working together to identify the genetic factors that contribute to RA -- with those from 1,282 people without RA (controls). The Swedish group compared 676 samples from the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA) with 673 controls.
Both groups' searches led them to a region of chromosome 9 containing two genes relevant to chronic inflammation: TRAF1 (encoding tumor necrosis factor receptor-associated factor 1) and C5 (encoding complement component 5).
"The whole-genome screening method lets us identify genes that contribute to disease-susceptibility without imposing our preconceived notions of the disease. We expected to come up with something new," says Elaine F. Remmers, Ph.D., of the Genetics and Genomics Branch of the NIAMS Intramural Research Program and an author of the study. "We were thrilled to find out that TRAF1-C5 showed association not only in the samples that we did with NARAC but also independently in the Swedish group. By combining our information, we were able to make a much stronger case [for a TRAF1-C5 association]. The combined evidence was pretty impressive."
Remmers says the TRAF1-C5 region was the third of three major susceptibility chromosomal regions for RA identified by their whole genome screen. The first two, HLA-DRB1 and PTPN22, had already been well established.
She says that it's not yet known how the genes in the TRAF1-C5 region influence RA risk. Nor can scientists say which of the two genes is causing the disease. "Actually, both genes are very interesting candidates," she says. "They both control inflammatory processes that really are relevant for the disease, so we could easily envision either of them playing a role -- or both."
The hope is that by learning more about the genes and their role in the disease, scientists may find clues to influencing treatment of the disease. "We are hoping that we will find variants in either of the genes that will lead us to new targets for therapy. Once we understand how the RA-associated variants work, we may be able interfere with the pathways the variants are influencing and either prevent the disease or block its progression."
According to coauthor Daniel Kastner, M.D., Ph.D., NIAMS clinical director and chief of the NIAMS Genetics and Genomics Branch, "The success of the study can be attributed in part to the productive, longstanding collaboration between NIAMS intramural researchers and other scientists that the Institute supports around the country." NARAC was established 10 years ago by coauthor Peter K. Gregersen, M.D., at the Feinstein Institute for Medical Research, the North Shore Long Island Jewish Health System, in order to facilitate the collection and analysis of RA genetic samples. Kastner was also a key early member of the NARAC, as were many other investigators at several academic health centers across the United States.
In addition to NIAMS, other support for the U.S. study came from the National Center for Research Resources, the Arthritis Foundation, grants from the Boas Family and the Eileen Ludwig Greenland Center for Rheumatoid Arthritis (Feinstein Institute for Medical Research), the Rosalind Russell Medical Research Center for Arthritis and the Kirkland Scholar Award (University of California, San Francisco).
Support for the Swedish arm of the study came from the Swedish Medical Research Council, the Swedish Council for Working Life and Social Research, the King Gustaf V's 80-Year Foundation, the Swedish Rheumatism Foundation, the Stockholm County Council, the AFA insurance company and the Agency for Science Technology and Research, Singapore.
The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, visit the NIAMS Web site at niams.nih/.
The National Center for Research Resources (NCRR) provides clinical and translational researchers with the training and tools they need to understand, detect, treat, and prevent a wide range of diseases. For more information about NCRR visit ncrr.nih/.
The National Institutes of Health (NIH) -- The Nation's Medical Research Agency -- includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit nih/.
Reference: Plenge RM et al. TRAF1-C5 as a risk locus for rheumatoid arthritis -- a genomewide study. NEJM 2007;357:1199 -1209.
Source: Trish Reynolds
NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases
Using the relatively new genome-wide association approach -- which makes it possible to analyze between 300,000 and 500,000 single nucleotide polymorphisms (SNPs, or small differences in DNA that are distributed throughout a person's genetic code) -- researchers in both countries searched for genetic differences in blood samples from people with RA compared to controls. The U.S. group compared 908 samples from patients provided by the North American Rheumatoid Arthritis Consortium (NARAC) -- a group of investigators working together to identify the genetic factors that contribute to RA -- with those from 1,282 people without RA (controls). The Swedish group compared 676 samples from the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA) with 673 controls.
Both groups' searches led them to a region of chromosome 9 containing two genes relevant to chronic inflammation: TRAF1 (encoding tumor necrosis factor receptor-associated factor 1) and C5 (encoding complement component 5).
"The whole-genome screening method lets us identify genes that contribute to disease-susceptibility without imposing our preconceived notions of the disease. We expected to come up with something new," says Elaine F. Remmers, Ph.D., of the Genetics and Genomics Branch of the NIAMS Intramural Research Program and an author of the study. "We were thrilled to find out that TRAF1-C5 showed association not only in the samples that we did with NARAC but also independently in the Swedish group. By combining our information, we were able to make a much stronger case [for a TRAF1-C5 association]. The combined evidence was pretty impressive."
Remmers says the TRAF1-C5 region was the third of three major susceptibility chromosomal regions for RA identified by their whole genome screen. The first two, HLA-DRB1 and PTPN22, had already been well established.
She says that it's not yet known how the genes in the TRAF1-C5 region influence RA risk. Nor can scientists say which of the two genes is causing the disease. "Actually, both genes are very interesting candidates," she says. "They both control inflammatory processes that really are relevant for the disease, so we could easily envision either of them playing a role -- or both."
The hope is that by learning more about the genes and their role in the disease, scientists may find clues to influencing treatment of the disease. "We are hoping that we will find variants in either of the genes that will lead us to new targets for therapy. Once we understand how the RA-associated variants work, we may be able interfere with the pathways the variants are influencing and either prevent the disease or block its progression."
According to coauthor Daniel Kastner, M.D., Ph.D., NIAMS clinical director and chief of the NIAMS Genetics and Genomics Branch, "The success of the study can be attributed in part to the productive, longstanding collaboration between NIAMS intramural researchers and other scientists that the Institute supports around the country." NARAC was established 10 years ago by coauthor Peter K. Gregersen, M.D., at the Feinstein Institute for Medical Research, the North Shore Long Island Jewish Health System, in order to facilitate the collection and analysis of RA genetic samples. Kastner was also a key early member of the NARAC, as were many other investigators at several academic health centers across the United States.
In addition to NIAMS, other support for the U.S. study came from the National Center for Research Resources, the Arthritis Foundation, grants from the Boas Family and the Eileen Ludwig Greenland Center for Rheumatoid Arthritis (Feinstein Institute for Medical Research), the Rosalind Russell Medical Research Center for Arthritis and the Kirkland Scholar Award (University of California, San Francisco).
Support for the Swedish arm of the study came from the Swedish Medical Research Council, the Swedish Council for Working Life and Social Research, the King Gustaf V's 80-Year Foundation, the Swedish Rheumatism Foundation, the Stockholm County Council, the AFA insurance company and the Agency for Science Technology and Research, Singapore.
The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, visit the NIAMS Web site at niams.nih/.
The National Center for Research Resources (NCRR) provides clinical and translational researchers with the training and tools they need to understand, detect, treat, and prevent a wide range of diseases. For more information about NCRR visit ncrr.nih/.
The National Institutes of Health (NIH) -- The Nation's Medical Research Agency -- includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit nih/.
Reference: Plenge RM et al. TRAF1-C5 as a risk locus for rheumatoid arthritis -- a genomewide study. NEJM 2007;357:1199 -1209.
Source: Trish Reynolds
NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases
Subchondral Bone Changes Contribute To Cartilage Damage And Loss
A recent study determined that bone area predicted the development of medial (inner side) and lateral (outer side) knee cartilage damage and loss of medial cartilage volume. Subchondral bone mineral density (BMD) was associated with medial defect development but not cartilage loss. Researchers believe subchondral bone changes and loss of cartilage contribute to the development of osteoarthritis (OA). Read details of the study online or in the July issue of Arthritis & Rheumatism, a journal published by Wiley-Blackwell on behalf of the American College of Rheumatology.
According to a report by the World Health Organization (WHO), 9.6% of men and 18% of women over 60 years of age worldwide have OA symptoms, making it a leading cause of disability. OA is caused by the gradual loss of cartilage and underlying bone, typically affecting the knee, hip, hand, and spine joints. The Centers for Disease Control and Prevention estimate that 4.3 million Americans over age 60 have symptomatic knee OA, the most common joint affected. In fact prior studies of U.S. and European populations (over 45 years of age) show higher rates of knee OA in 14.1% of men and 22.8% of women (WHO report).
Ph.D. candidate and lead author of the study, Dawn Dore??, enrolled 341 participants in their prospective study. Participants had a mean age of 63 years and provided measurements of tibial knee cartilage volume, cartilage defects, and bone area using magnetic resonance imaging (MRI). The tibial subchondral BMD was determined using dual x-ray absorptiometry (DXA). Follow-up measurements of cartilage volume and defects were taken 2.7 years later.
Study results found that baseline bone area positively predicted cartilage defect development at the medial and lateral tibial sites (odds ratio [OR] 1.6 and OR 2.4 per 1 SD increase, respectively). Cartilage volume loss at the medial tibial site was also positively predicted by baseline bone area (?? -34.9 per 1 SD increase). However, baseline subchondral BMD positively predicted cartilage defect development at the medial tibial site only (OR 1.6 per 1 SD increase) and was not associated with loss of cartilage.
"Our results clearly show bone area was a predictor of cartilage defect development in the inner and outer knee, as well as medial cartilage volume loss," said Ms. Dore??. "We found that subchondral BMD only predicted defect development on the inside of the knee, but not cartilage loss". Researchers noted that the associations were independent of each other and suggest there are multiple mechanisms where changes in subchondral bone could lead to cartilage damage. "With the ability to predict those at risk of developing knee OA, early interventions can be offered to patients in order to lessen the disabling affects of this disease," concluded Ms. Dore??.
Source: Wiley - Blackwell
According to a report by the World Health Organization (WHO), 9.6% of men and 18% of women over 60 years of age worldwide have OA symptoms, making it a leading cause of disability. OA is caused by the gradual loss of cartilage and underlying bone, typically affecting the knee, hip, hand, and spine joints. The Centers for Disease Control and Prevention estimate that 4.3 million Americans over age 60 have symptomatic knee OA, the most common joint affected. In fact prior studies of U.S. and European populations (over 45 years of age) show higher rates of knee OA in 14.1% of men and 22.8% of women (WHO report).
Ph.D. candidate and lead author of the study, Dawn Dore??, enrolled 341 participants in their prospective study. Participants had a mean age of 63 years and provided measurements of tibial knee cartilage volume, cartilage defects, and bone area using magnetic resonance imaging (MRI). The tibial subchondral BMD was determined using dual x-ray absorptiometry (DXA). Follow-up measurements of cartilage volume and defects were taken 2.7 years later.
Study results found that baseline bone area positively predicted cartilage defect development at the medial and lateral tibial sites (odds ratio [OR] 1.6 and OR 2.4 per 1 SD increase, respectively). Cartilage volume loss at the medial tibial site was also positively predicted by baseline bone area (?? -34.9 per 1 SD increase). However, baseline subchondral BMD positively predicted cartilage defect development at the medial tibial site only (OR 1.6 per 1 SD increase) and was not associated with loss of cartilage.
"Our results clearly show bone area was a predictor of cartilage defect development in the inner and outer knee, as well as medial cartilage volume loss," said Ms. Dore??. "We found that subchondral BMD only predicted defect development on the inside of the knee, but not cartilage loss". Researchers noted that the associations were independent of each other and suggest there are multiple mechanisms where changes in subchondral bone could lead to cartilage damage. "With the ability to predict those at risk of developing knee OA, early interventions can be offered to patients in order to lessen the disabling affects of this disease," concluded Ms. Dore??.
Source: Wiley - Blackwell
Molecular Gatekeeper Of Arthritis Identified
Elimination of a molecular gatekeeper leads to the development of arthritis in mice, scientists report in a study published in The Journal of Experimental Medicine. The newly discovered gatekeeper is a protein that determines the fate - survival or death - of damaging cells that mistakenly attack the body's own tissues and lead to autoimmune disorders such as arthritis.
Better understanding how arthritis develops will offer scientists an opportunity to explore new types of treatments for patients whose arthritis has not been effectively treated with current therapies.
"This finding is an encouraging step forward for researchers, clinicians and arthritis sufferers, many of whom fail available therapies," said lead researcher Frances Lund, Ph.D., professor of Medicine in the Division of Allergy/Immunology and Rheumatology at the University of Rochester Medical Center. "An added bonus is that this finding may help in the search for new treatments for other autoimmune disorders, such as lupus."
The protein at the center of the new finding, known as G?±q (G alpha q), is part of a larger signaling pathway that Lund and collaborators from across the United States and China investigated in mice. G?±q regulates B cells, one type of immune cell that the body maintains to fight off invaders like bacteria, viruses and parasites. While most B cells help defend the body, some B cells are autoreactive - they turn against the body's own tissues.
In mice, G?±q normally stops autoreactive B cells from building up in tissues by suppressing the pro-survival signaling pathway uncovered by Lund's team. When G?±q is eliminated, autoreactive B cells are able to pass through internal 'checkpoints' that typically get rid of these harmful cells, creating a buildup of the cells that contributes to the development of autoimmune disease.
Several new studies expanding on the current finding are in the works, including testing whether drug compounds that alter the expression or activity of G?±q in mice can slow the development of autoimmunity. Beyond preclinical testing in mice, researchers also hope to start screening G?±q levels in patients to learn more about how the protein works in humans.
According to Lund, "There is a subset of cardiac patients who, due to an inherited genetic mutation, have increased levels of G?±q. We are now looking to see if some arthritis patients have mutations that favor decreased levels of G?±q. If we find these patients, someday we may be able to design targeted, personalized therapy for this subpopulation of arthritis sufferers."
"In the past few decades, nearly all of the really important advances in rheumatology have started with basic studies like this one," said Richard John Looney, M.D., a rheumatologist and professor of Medicine at the University of Rochester Medical Center. "I will be particularly interested in the translational studies that will be starting soon, as they may result in new applications such as assessing the risk someone may develop lupus or other autoimmune diseases."
Lund's research also led to the creation of a new mouse model of arthritis. By eliminating G?±q, the disease just happens in mice, as opposed to previous mouse models which require injecting an antigen or foreign body, such as collagen, into mice to trigger an immune response. The new model more closely mirrors how autoimmunity starts and progresses in humans, and may be used in the future to test new drugs in development.
"Our goal is to move the knowledge we've gained from basic research to meaningful results that will ultimately help patients, and our main finding coupled with the creation of an improved mouse model puts us in a very strong position to do that," said Lund.
As with many discoveries, the new finding came about unexpectedly. Scientists in Lund's lab were looking at cell migration to try to identify the molecular signals that cause inflammation in tissues in G?±q knockout mice. They noticed that as they grew older, the mice's joints swelled and it appeared as though they were getting arthritis. Lund's team pursued the lead, which led to the discovery of the protein's role in the development of the disease and the creation of the new mouse model.
In addition to Lund, Ravi Misra, Ph.D., Betty Mousseau, Kim Kusser, and Troy Randall, Ph.D., from the University of Rochester Medical Center contributed to the research. Scientists from Sichuan University, China, the University of Washington, Seattle Children's Research Institute, the Trudeau Institute, the University of Massachusetts Medical School, and the University of California, San Diego, School of Medicine were also part of the research team. Biogen Idec and Human Genome Sciences provided biologic drugs that were used to test whether B cells in the G?±q deficient mice were responsible for causing arthritis in the mice.
The research was funded by the National Institute of Allergy and Infectious Disease at the National Institutes of Health and the University of Rochester Medical Center.
Source:
Emily Boynton
University of Rochester Medical Center
Better understanding how arthritis develops will offer scientists an opportunity to explore new types of treatments for patients whose arthritis has not been effectively treated with current therapies.
"This finding is an encouraging step forward for researchers, clinicians and arthritis sufferers, many of whom fail available therapies," said lead researcher Frances Lund, Ph.D., professor of Medicine in the Division of Allergy/Immunology and Rheumatology at the University of Rochester Medical Center. "An added bonus is that this finding may help in the search for new treatments for other autoimmune disorders, such as lupus."
The protein at the center of the new finding, known as G?±q (G alpha q), is part of a larger signaling pathway that Lund and collaborators from across the United States and China investigated in mice. G?±q regulates B cells, one type of immune cell that the body maintains to fight off invaders like bacteria, viruses and parasites. While most B cells help defend the body, some B cells are autoreactive - they turn against the body's own tissues.
In mice, G?±q normally stops autoreactive B cells from building up in tissues by suppressing the pro-survival signaling pathway uncovered by Lund's team. When G?±q is eliminated, autoreactive B cells are able to pass through internal 'checkpoints' that typically get rid of these harmful cells, creating a buildup of the cells that contributes to the development of autoimmune disease.
Several new studies expanding on the current finding are in the works, including testing whether drug compounds that alter the expression or activity of G?±q in mice can slow the development of autoimmunity. Beyond preclinical testing in mice, researchers also hope to start screening G?±q levels in patients to learn more about how the protein works in humans.
According to Lund, "There is a subset of cardiac patients who, due to an inherited genetic mutation, have increased levels of G?±q. We are now looking to see if some arthritis patients have mutations that favor decreased levels of G?±q. If we find these patients, someday we may be able to design targeted, personalized therapy for this subpopulation of arthritis sufferers."
"In the past few decades, nearly all of the really important advances in rheumatology have started with basic studies like this one," said Richard John Looney, M.D., a rheumatologist and professor of Medicine at the University of Rochester Medical Center. "I will be particularly interested in the translational studies that will be starting soon, as they may result in new applications such as assessing the risk someone may develop lupus or other autoimmune diseases."
Lund's research also led to the creation of a new mouse model of arthritis. By eliminating G?±q, the disease just happens in mice, as opposed to previous mouse models which require injecting an antigen or foreign body, such as collagen, into mice to trigger an immune response. The new model more closely mirrors how autoimmunity starts and progresses in humans, and may be used in the future to test new drugs in development.
"Our goal is to move the knowledge we've gained from basic research to meaningful results that will ultimately help patients, and our main finding coupled with the creation of an improved mouse model puts us in a very strong position to do that," said Lund.
As with many discoveries, the new finding came about unexpectedly. Scientists in Lund's lab were looking at cell migration to try to identify the molecular signals that cause inflammation in tissues in G?±q knockout mice. They noticed that as they grew older, the mice's joints swelled and it appeared as though they were getting arthritis. Lund's team pursued the lead, which led to the discovery of the protein's role in the development of the disease and the creation of the new mouse model.
In addition to Lund, Ravi Misra, Ph.D., Betty Mousseau, Kim Kusser, and Troy Randall, Ph.D., from the University of Rochester Medical Center contributed to the research. Scientists from Sichuan University, China, the University of Washington, Seattle Children's Research Institute, the Trudeau Institute, the University of Massachusetts Medical School, and the University of California, San Diego, School of Medicine were also part of the research team. Biogen Idec and Human Genome Sciences provided biologic drugs that were used to test whether B cells in the G?±q deficient mice were responsible for causing arthritis in the mice.
The research was funded by the National Institute of Allergy and Infectious Disease at the National Institutes of Health and the University of Rochester Medical Center.
Source:
Emily Boynton
University of Rochester Medical Center
Singapore Health Sciences Authority Alerts Consumers To An Illegal Product -"ASAM URAT FLU TULANG, PJ. DEWANDARU"
The Health Sciences Authority (HSA) warns consumers not to take an illegal medicinal product labelled as "Asam Urat Flu Tulang, PJ. Dewandaru", which has been found to be adulterated with Western medicinal ingredients, diclofenac, dexamethasone and paracetamol. These medicinal ingredients have the potential to cause serious adverse effects. In particular, diclofenac and dexamethasone should only be taken under strict medical supervision as prescribed by a medical doctor.
Adverse Drug Reaction Detected
HSA was alerted to the adulterated illegal product through a report of adverse drug reaction [ADR] submitted by a doctor, who suspected that a young female patient had developed an allergic drug reaction comprising symptoms of skin rash, eye swelling and liver inflammation after consuming the herbal product. The product, "Asam Urat Flu Tulang, PJ. Dewandaru", is labelled with claims to treat joint pain, rheumatism and arthritis.
Our investigation revealed that the product was purchased in Indonesia and brought into Singapore by the patient for personal use. While there is no evidence that this illegal product is on sale in Singapore, consumers are advised to be vigilant and inform the HSA immediately if they become aware that this product is sold locally.
The adulterants found are potent Western medicinal ingredients. Dexamethasone is a corticosteroid used in the treatment of allergic disorders and inflammatory conditions. Prolonged use without medical supervision can cause serious adverse effects such as hypertension, blood sugar disorders, osteoporosis and Cushing's syndrome. Diclofenac is an anti-inflammatory agent used for the treatment of joint pain and arthritis and can cause gastric bleeding and blood disorders when used unsupervised. Paracetamol is a painkiller and may cause adverse effects such as liver and kidney problems in susceptible individuals who unwittingly take it continuously for prolonged periods.
Consumer Advisory
Consumers who have purchased and consumed this illegal product are advised to stop taking it and seek advice from doctors if they feel unwell.
Consumers are reminded of the risks of purchasing medicinal and health products from dubious sources such as street peddlers and the Internet. In addition, consumers are advised to be wary of products that have claims that sound too good to be true or claim to treat medical conditions, especially those that are supported only by testimonials from users.
Diclofenac and dexamethasone are substances controlled under the Poisons Act. It is an offence for an unlicensed person to import, sell or possess for sale any product containing these two substances. Anyone found guilty of an offence under the Poisons Act is liable to a fine of up to $10,000 and/or imprisonment for a term of up to two years. It is also an offence under the Medicines Act for anyone to deal with a product containing a western medicinal ingredient, such as paracetamol without an appropriate product licence. Offenders are liable on conviction, to a fine not exceeding $5,000, and/or to imprisonment for a term not exceeding two years.
HSA encourages the public to report any suspicious sales of illegal products to the Compliance Branch of the Centre for Drug Administration, Health Products Regulation Group, which can be contacted at tel: 6866-3485 during office hours (Monday to Friday) or fax to 6478-9065.
See full article:
click here
Singapore Health Sciences Authority
hsa.sg
Adverse Drug Reaction Detected
HSA was alerted to the adulterated illegal product through a report of adverse drug reaction [ADR] submitted by a doctor, who suspected that a young female patient had developed an allergic drug reaction comprising symptoms of skin rash, eye swelling and liver inflammation after consuming the herbal product. The product, "Asam Urat Flu Tulang, PJ. Dewandaru", is labelled with claims to treat joint pain, rheumatism and arthritis.
Our investigation revealed that the product was purchased in Indonesia and brought into Singapore by the patient for personal use. While there is no evidence that this illegal product is on sale in Singapore, consumers are advised to be vigilant and inform the HSA immediately if they become aware that this product is sold locally.
The adulterants found are potent Western medicinal ingredients. Dexamethasone is a corticosteroid used in the treatment of allergic disorders and inflammatory conditions. Prolonged use without medical supervision can cause serious adverse effects such as hypertension, blood sugar disorders, osteoporosis and Cushing's syndrome. Diclofenac is an anti-inflammatory agent used for the treatment of joint pain and arthritis and can cause gastric bleeding and blood disorders when used unsupervised. Paracetamol is a painkiller and may cause adverse effects such as liver and kidney problems in susceptible individuals who unwittingly take it continuously for prolonged periods.
Consumer Advisory
Consumers who have purchased and consumed this illegal product are advised to stop taking it and seek advice from doctors if they feel unwell.
Consumers are reminded of the risks of purchasing medicinal and health products from dubious sources such as street peddlers and the Internet. In addition, consumers are advised to be wary of products that have claims that sound too good to be true or claim to treat medical conditions, especially those that are supported only by testimonials from users.
Diclofenac and dexamethasone are substances controlled under the Poisons Act. It is an offence for an unlicensed person to import, sell or possess for sale any product containing these two substances. Anyone found guilty of an offence under the Poisons Act is liable to a fine of up to $10,000 and/or imprisonment for a term of up to two years. It is also an offence under the Medicines Act for anyone to deal with a product containing a western medicinal ingredient, such as paracetamol without an appropriate product licence. Offenders are liable on conviction, to a fine not exceeding $5,000, and/or to imprisonment for a term not exceeding two years.
HSA encourages the public to report any suspicious sales of illegal products to the Compliance Branch of the Centre for Drug Administration, Health Products Regulation Group, which can be contacted at tel: 6866-3485 during office hours (Monday to Friday) or fax to 6478-9065.
See full article:
click here
Singapore Health Sciences Authority
hsa.sg
NICE Appraisal Of Rituximab And Adalimumab For The Treatment Of Arthritis
The National Institute for Health and Clinical Excellence (NICE) has published
final guidance on the use of rituximab (Mabthera) for the treatment of rheumatoid
arthritis and adalimumab (Humira) for the treatment of psoriatic arthritis, as part of its
rapid single technology appraisal (STA) work programme.
NICE recommends:
-- Rituximab in combination with methotrexate is recommended as a treatment
option for adults with severe active rheumatoid arthritis who have had an
inadequate response to or intolerance of other disease modifying anti-
rheumatic drugs. This should include treatment with at least one tumour
necrosis factor (TNF) inhibitor therapy
-- Treatment with rituximab plus methotrexate should be continued only if there
is an adequate response following initiation of therapy
-- Adalimumab is recommended as a treatment option for adults with active and
progressive psoriatic arthritis when the person has peripheral arthritis with
three or more tender joints and three or more swollen joints, and the psoriatic
arthritis has not responded to adequate trials of at least two standard disease-
modifying anti-rheumatic drugs
-- Adalimumab treatment should be discontinued after 12 weeks in adults whose
psoriatic arthritis has not shown an adequate response
Andrew Dillon, Executive Lead for the appraisal said: "Following further
clarification from the manufacturer on the economic analysis of rituximab, the
committee has assessed that these drugs represent the right approach for the NHS
to take in the treatment of two severe forms of arthritis. It is estimated that up to 1%
of the population suffers from rheumatoid or psoriatic arthritis, which are both very
distressing, causing a great deal of pain or discomfort and impacting on an
individual's ability to go about their daily life. The approval of both of these drugs is
good news for anyone suffering from rheumatoid or psoriatic arthritis - by
recommending the use of these drugs, people in England and Wales with these
conditions can be reassured that they have access to effective treatments when they
need them."
About NICE
1. The National Institute for Health and Clinical Excellence (NICE) is the independent
organisation responsible for providing national guidance on the promotion of good health
and the prevention and treatment of ill health.
2. NICE produces guidance in three areas of health:
-- public health - guidance on the promotion of good health and the prevention of ill
health for those working in the NHS, local authorities and the wider public and
voluntary sector
-- health technologies - guidance on the use of new and existing medicines,
treatments and procedures within the NHS
-- clinical practice - guidance on the appropriate treatment and care of people with
specific diseases and conditions within the NHS.
About the guidance
3. The adalimumab and rituximab guidance is available at nice.uk/TA125 and
nice.uk/TA126.
4. Rheumatoid arthritis (RA) is a chronic, disabling condition characterised by inflammation
of the synovial tissue of the joints, causing pain, swelling and stiffness and progressive
joint destruction. It affects between 0.5% and 1% of the population, or approximately
400,000 people in England and Wales. Of these, approximately 15% have severe
disease. RA affects three times as many women as men and has a peak age of onset of
40-70 years.
5. Psoriatic arthritis (psoriatic arthropathy) is an inflammatory joint disease closely
associated with the skin disease psoriasis. An estimated 5-7% of all people with
psoriasis have psoriatic arthritis, but it is much more common in those with extensive
psoriasis. Psoriatic arthritis has an overall prevalence of between 0.1% and 1%. It affects
men and women equally and its incidence peaks between the ages of 30 and 55 years.
nice.uk
View drug information on Humira.
final guidance on the use of rituximab (Mabthera) for the treatment of rheumatoid
arthritis and adalimumab (Humira) for the treatment of psoriatic arthritis, as part of its
rapid single technology appraisal (STA) work programme.
NICE recommends:
-- Rituximab in combination with methotrexate is recommended as a treatment
option for adults with severe active rheumatoid arthritis who have had an
inadequate response to or intolerance of other disease modifying anti-
rheumatic drugs. This should include treatment with at least one tumour
necrosis factor (TNF) inhibitor therapy
-- Treatment with rituximab plus methotrexate should be continued only if there
is an adequate response following initiation of therapy
-- Adalimumab is recommended as a treatment option for adults with active and
progressive psoriatic arthritis when the person has peripheral arthritis with
three or more tender joints and three or more swollen joints, and the psoriatic
arthritis has not responded to adequate trials of at least two standard disease-
modifying anti-rheumatic drugs
-- Adalimumab treatment should be discontinued after 12 weeks in adults whose
psoriatic arthritis has not shown an adequate response
Andrew Dillon, Executive Lead for the appraisal said: "Following further
clarification from the manufacturer on the economic analysis of rituximab, the
committee has assessed that these drugs represent the right approach for the NHS
to take in the treatment of two severe forms of arthritis. It is estimated that up to 1%
of the population suffers from rheumatoid or psoriatic arthritis, which are both very
distressing, causing a great deal of pain or discomfort and impacting on an
individual's ability to go about their daily life. The approval of both of these drugs is
good news for anyone suffering from rheumatoid or psoriatic arthritis - by
recommending the use of these drugs, people in England and Wales with these
conditions can be reassured that they have access to effective treatments when they
need them."
About NICE
1. The National Institute for Health and Clinical Excellence (NICE) is the independent
organisation responsible for providing national guidance on the promotion of good health
and the prevention and treatment of ill health.
2. NICE produces guidance in three areas of health:
-- public health - guidance on the promotion of good health and the prevention of ill
health for those working in the NHS, local authorities and the wider public and
voluntary sector
-- health technologies - guidance on the use of new and existing medicines,
treatments and procedures within the NHS
-- clinical practice - guidance on the appropriate treatment and care of people with
specific diseases and conditions within the NHS.
About the guidance
3. The adalimumab and rituximab guidance is available at nice.uk/TA125 and
nice.uk/TA126.
4. Rheumatoid arthritis (RA) is a chronic, disabling condition characterised by inflammation
of the synovial tissue of the joints, causing pain, swelling and stiffness and progressive
joint destruction. It affects between 0.5% and 1% of the population, or approximately
400,000 people in England and Wales. Of these, approximately 15% have severe
disease. RA affects three times as many women as men and has a peak age of onset of
40-70 years.
5. Psoriatic arthritis (psoriatic arthropathy) is an inflammatory joint disease closely
associated with the skin disease psoriasis. An estimated 5-7% of all people with
psoriasis have psoriatic arthritis, but it is much more common in those with extensive
psoriasis. Psoriatic arthritis has an overall prevalence of between 0.1% and 1%. It affects
men and women equally and its incidence peaks between the ages of 30 and 55 years.
nice.uk
View drug information on Humira.
Pediatric Rheumatology: Mortality Rates Significantly Lower Than Previously Reported
A recent study by researchers from the Cleveland Clinic found that the overall mortality rate in the U.S. for all pediatric patients with rheumatic diseases was not worse than the age and sex-adjusted population. Furthermore, mortality rates were significantly lower than reported in previous studies of rheumatic diseases and conditions that are associated with increased mortality. Details of the study appear in the February issue of Arthritis & Rheumatism, a journal published by Wiley-Blackwell on behalf of the American College of Rheumatology.
The Childhood Arthritis and Rheumatology Research Alliance (CARRA) estimates that 300,000 children in the U.S. suffer from some form of arthritis or rheumatic disease. According to CARRA, childhood arthritis is the #1 cause of acquired disability in children and is the 6th most common chronic childhood disease.
While rheumatic diseases present well-known risks to health, function, and quality of life, several conditions - juvenile rheumatoid arthritis, childhood systemic lupus erythematosus, dermatomyositis, various vasculitides, and systemic sclerosis are associated in various studies with a small but significant increase in mortality.
The Cleveland Clinic study team, however, maintains that previous mortality studies were relatively small, reported mortality outcomes only on specific diseases, had a follow up time of less than 10 years, and were mostly conducted prior to the 1990s, when new and improved drug treatments emerged. The team suggests that larger studies may also be flawed because most were based on physician surveys, without strategies to verify response.
To determine the mortality rates, risks, and causes of death associated with pediatric rheumatic diseases in the U.S., the researchers examined the world's largest rheumatology registry, the Pediatric Rheumatology Disease Registry (PRDR), which includes 49,023 patients from 62 centers who were newly diagnosed between 1992 and 2001. Identifiers were matched with the Social Security Death Index censored for March 2005. Death certificates, referring physicians, and medical records confirmed deaths. Causes of death were derived by chart review or from the death certificate.
After excluding patients with malignancy, 110 deaths were identified among 48,885 patients in the PRDR registry. This number was significantly lower than the expected mortality from the age- and sex-adjusted U.S. population especially among 18,111 patients who were followed up for at least 9 years. The standardized mortality ratio was notably greater for systemic lupus erythematosus and dermatomyositis but not for systemic juvenile rheumatoid arthritis and was markedly less for pain syndromes. Most of the deceased with inflammatory disease died of their disease or disease complications, while many of the deceased with pain syndromes died of non-natural causes.
"One possible cause of the increased survival in the present study compared with previous studies may be the improved treatment that was introduced in the 1990s, said the lead author of the study Philip Hashkes, M.D., M.Sc. "Since the information in the PRDR was limited, we could not explore in depth for risk factors or early predictors of mortality. This and continued follow-up of this cohort for mortality trends should be investigated in future studies."
This study was funded by the Northeast Ohio Chapter of the Arthritis Foundation.
Article: "Mortality Outcomes in Pediatric Rheumatology in the US." Philip J. Hashkes, Bridget M. Wright, Michael S. Lauer, Sarah E. Worley, Anne S. Tang, Philip A. Roettcher, and Suzanne L. Bowyer. Arthritis & Rheumatism; Published Online: January 28, 2010 (DOI: 10.1002/art.27218); Print Issue Date: February 2010.
Source:
Dawn Peters
Wiley-Blackwell
The Childhood Arthritis and Rheumatology Research Alliance (CARRA) estimates that 300,000 children in the U.S. suffer from some form of arthritis or rheumatic disease. According to CARRA, childhood arthritis is the #1 cause of acquired disability in children and is the 6th most common chronic childhood disease.
While rheumatic diseases present well-known risks to health, function, and quality of life, several conditions - juvenile rheumatoid arthritis, childhood systemic lupus erythematosus, dermatomyositis, various vasculitides, and systemic sclerosis are associated in various studies with a small but significant increase in mortality.
The Cleveland Clinic study team, however, maintains that previous mortality studies were relatively small, reported mortality outcomes only on specific diseases, had a follow up time of less than 10 years, and were mostly conducted prior to the 1990s, when new and improved drug treatments emerged. The team suggests that larger studies may also be flawed because most were based on physician surveys, without strategies to verify response.
To determine the mortality rates, risks, and causes of death associated with pediatric rheumatic diseases in the U.S., the researchers examined the world's largest rheumatology registry, the Pediatric Rheumatology Disease Registry (PRDR), which includes 49,023 patients from 62 centers who were newly diagnosed between 1992 and 2001. Identifiers were matched with the Social Security Death Index censored for March 2005. Death certificates, referring physicians, and medical records confirmed deaths. Causes of death were derived by chart review or from the death certificate.
After excluding patients with malignancy, 110 deaths were identified among 48,885 patients in the PRDR registry. This number was significantly lower than the expected mortality from the age- and sex-adjusted U.S. population especially among 18,111 patients who were followed up for at least 9 years. The standardized mortality ratio was notably greater for systemic lupus erythematosus and dermatomyositis but not for systemic juvenile rheumatoid arthritis and was markedly less for pain syndromes. Most of the deceased with inflammatory disease died of their disease or disease complications, while many of the deceased with pain syndromes died of non-natural causes.
"One possible cause of the increased survival in the present study compared with previous studies may be the improved treatment that was introduced in the 1990s, said the lead author of the study Philip Hashkes, M.D., M.Sc. "Since the information in the PRDR was limited, we could not explore in depth for risk factors or early predictors of mortality. This and continued follow-up of this cohort for mortality trends should be investigated in future studies."
This study was funded by the Northeast Ohio Chapter of the Arthritis Foundation.
Article: "Mortality Outcomes in Pediatric Rheumatology in the US." Philip J. Hashkes, Bridget M. Wright, Michael S. Lauer, Sarah E. Worley, Anne S. Tang, Philip A. Roettcher, and Suzanne L. Bowyer. Arthritis & Rheumatism; Published Online: January 28, 2010 (DOI: 10.1002/art.27218); Print Issue Date: February 2010.
Source:
Dawn Peters
Wiley-Blackwell
Humira(reg) (Adalimumab) Improved Symptoms Of Psoriatic Arthritis And Ankylosing Spondylitis
Preliminary data from two studies showing encouraging results in treating psoriatic arthritis and ankylosing spondylitis with HUMIRA(reg) (adalimumab) 40 mg every other week were presented today at the European League Against Rheumatism (EULAR) annual congress in Berlin. Patients with psoriatic arthritis responded to HUMIRA treatment as early as two weeks after the initial dose showing significant improvement in both the signs and symptoms of the joint disease and skin manifestations with continued improvements at 12 weeks.
Analysis of a separate 12-week study shows that HUMIRA significantly improves spinal symptoms in patients with active ankylosing spondylitis after only one dose.
"The findings of these two studies are significant because they validate our research to assess HUMIRA's potential to treat other autoimmune diseases in addition to rheumatoid arthritis," said James B. Lefkowith, M.D., divisional vice president, development, Abbott Immunology.
HUMIRA PROVIDED JOINT AND SKIN IMPROVEMENT IN PSORIATIC ARTHRITIS
Fifteen patients with active psoriatic arthritis were treated with HUMIRA 40 mg every other week, in this open-label trial, and observed over a 12-week period to evaluate the potential therapeutic effects of the treatment. After two weeks, significant improvements were seen in the signs and symptoms of the joint disease and skin manifestations associated with disease. Further improvements in the skin and joint disease were evident at 12 weeks.
Forty-two percent of patients treated with HUMIRA experienced an ACR 20 response after only one dose. ACR (American College of Rheumatology) 20, 50 and 70 criteria represent percent improvement in tender and swollen joint counts and other relevant clinical measures. Also after two weeks, 77 percent of patients experienced at least 25 percent improvement in health-related quality of life as measured by the Health Assessment Questionnaire (HAQ) disability index, which is designed to capture patients' assessment of activities of daily living such as grooming, dressing and walking. Health-related quality of life questionnaires are used to measure the impact of chronic illness on a patient's life.
Further improvement was seen at 12 weeks in both the arthritic symptoms and in health-related quality of life. Sixty-six percent of patients achieved an ACR 20 response and approximately 30 percent attained ACR 50. The HAQ disability index also showed further improvement at week 12 compared to week two.
Substantial improvements also were evident in the skin disease of these patients. Target lesion scores, an evaluation of the severity of a single psoriasis lesion, improved by nearly 30 percent after one dose. After 12 weeks, the target lesion score improved by more than 70 percent.
"The initial results and analysis of this study show that HUMIRA provided significant benefit to many patients with psoriatic arthritis shortly after the first dose," said Christopher T. Ritchlin, M.D., associate professor and lead investigator, University of Rochester, Rochester, New York. "While more research is necessary, these early findings are promising and support HUMIRA's potential as a treatment for psoriatic arthritis."
ABOUT PSORIATIC ARTHRITIS
Psoriatic arthritis is an inflammatory arthritis that is associated with the skin condition psoriasis. It causes inflammation and stiffness in and around the joints, including the knees, wrists, ankles, lower back and neck. Psoriatic arthritis may stem from an autoimmune disorder in which a human protein, tumor necrosis factor-alpha (TNF-???), accumulates in the joints and initiates an inflammatory response that causes swelling and pain.
If left untreated, psoriatic arthritis can be a progressively disabling disease. Epidemiological studies indicate that psoriatic arthritis affects as many as 30 percent of people who have psoriasis, a non-contagious, chronic skin disease characterized by red plaques covered with white scales. Common symptoms of psoriatic arthritis include varying degrees of psoriasis activity along with stiffness, pain, swelling and tenderness of the joints that can lead to a reduced range of motion and potential severe joint destruction.
HUMIRA IMPROVED SYMPTOMS OF ACTIVE ANKYLOSING SPONDYLITIS
To examine the potential therapeutic effects of HUMIRA in patients with non-steroidal anti-inflammatory drug (NSAID)-refractory ankylosing spondylitis (i.e. patients not readily responding to NSAID therapy), researchers studied 10 patients over a 12-week period that received HUMIRA 40 mg every other week. In this open label study, all 10 patients suffered from spinal pain.
HUMIRA treatment induced a positive response in patients after the first dose, with further improvement at the end of the initial 12-week therapy, as measured by Assessment of Ankylosing Spondylitis (ASAS) criteria. ASAS evaluates four primary categories: function, pain, patient's global assessment and inflammation. Scores of ASAS20, ASAS40 and ASAS70 indicate corresponding symptom improvement percentages in at least three of the evaluation categories with no worsening in the remaining category.
The majority of patients in the trial experienced improvement in their symptoms with 70 percent achieving a score of ASAS20, 50 percent reached ASAS40 and 20 percent attained ASAS70.
Also at week 12, 50 percent of the patients experienced 50 percent or greater improvement in scores according to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), a patient-assessed composite index of disease activity measuring pain, stiffness and fatigue.
HUMIRA was well tolerated by patients in the study and no serious infections occurred during the study.
ABOUT ANKYLOSING SPONDYLITIS
Ankylosing spondylitis (AS), or arthritis of the spine, is thought to be an autoimmune disorder in which a human protein has been suggested to play a role in the disease development. As one of the many forms of inflammatory arthritis known as spondyloarthropathies, AS is a chronic disease that primarily affects the spine but can also affect other joints and ligaments, resulting in severe joint and back stiffness and deformity over time.
It is estimated that between 350,000 and one million people in the United States are affected by AS or a related disease and nearly three million in the European community.
Spondyloarthropathies are arthritic in nature, but unlike many other rheumatic conditions, they affect young adults and commonly begin before the age of 35.
ABOUT HUMIRA
HUMIRA is the first human monoclonal antibody available in Europe for RA, and the first tumor necrosis factor alpha (TNF-B) antagonist approved in Europe with an indication for use with methotrexate or as monotherapy. HUMIRA resembles antibodies normally found in the body. It works by blocking TNF-B, a protein that plays a central role in the inflammatory responses of autoimmune diseases such as RA.
Available in many countries, HUMIRA is indicated for the treatment of moderate to severe, active RA in adult patients when the response to disease modifying anti-rheumatic drugs (DMARDs), including methotrexate, has been inadequate.
To ensure maximum efficacy, HUMIRA is given in combination with methotrexate. In Europe, HUMIRA can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate. The European Medicines Evaluation Agency (EMEA) issued a positive opinion in April to authorize a label extension for HUMIRA for use in the treatment of adult RA patients for reducing the rate of progression of joint damage and to improve physical function. Such authorizations generally occur approximately 90 days after the issuance of the EMEA opinion.
Abbott received a positive opinion from the EMEA in May 2003 for the treatment of adult RA and was granted European Union approval to market HUMIRA in September 2003. HUMIRA received approval from the U.S. Food and Drug Administration on December 31, 2002. To date, HUMIRA has been approved in 41 countries and launched in 26.
The recommended dose of HUMIRA is 40 mg every other week by subcutaneous injection (a shot beneath the skin). Abbott offers HUMIRA in specially designed pre-filled syringes so patients do not have to mix and measure the medicine or leave their homes for treatment. The pre-filled syringe features handles and a plunger head designed for use by patients whose hands have been affected by their RA.
At the present time, HUMIRA has not received regulatory approval for the treatment of psoriatic arthritis or AS. Clinical trials are currently underway in autoimmune diseases.
IMPORTANT SAFETY INFORMATION
Common adverse events (>1/100 and 1/10 patients.
Patients must be monitored closely for infections, including tuberculosis (TB), before, during and after treatment with HUMIRA. Treatment should not be initiated in patients with active infections until infections are controlled. Patients who develop new infections while using HUMIRA should be monitored closely. HUMIRA should not be used by patients with active TB or other severe infections such as sepsis and opportunistic infections. HUMIRA should be discontinued if a patient develops a new serious infection until infections are controlled. Physicians should exercise caution when considering use of HUMIRA in patients with a history of recurring infection or with underlying conditions that may predispose patients to infections.
TNF-antagonists, including HUMIRA, have been associated in rare cases with exacerbation of clinical symptoms and/or radiographic evidence of demyelinating disease. Prescribers should exercise caution in considering the use of HUMIRA in patients with pre-existing or recent-onset central nervous system demyelinating disorders.
HUMIRA should be used with caution in patients with mild heart failure, and is contraindicated in patients with moderate or severe heart failure. HUMIRA must be discontinued in patients who develop new or worsening symptoms of congestive heart failure.
About Abbott
Abbott Laboratories is a global, broad-based health care company devoted to the discovery, development, manufacture and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. The company employs more than 55,000 people and markets its products in more than 130 countries.
More information about Abbott Immunology is available at abbottimmunology/.
View drug information on Humira.
Analysis of a separate 12-week study shows that HUMIRA significantly improves spinal symptoms in patients with active ankylosing spondylitis after only one dose.
"The findings of these two studies are significant because they validate our research to assess HUMIRA's potential to treat other autoimmune diseases in addition to rheumatoid arthritis," said James B. Lefkowith, M.D., divisional vice president, development, Abbott Immunology.
HUMIRA PROVIDED JOINT AND SKIN IMPROVEMENT IN PSORIATIC ARTHRITIS
Fifteen patients with active psoriatic arthritis were treated with HUMIRA 40 mg every other week, in this open-label trial, and observed over a 12-week period to evaluate the potential therapeutic effects of the treatment. After two weeks, significant improvements were seen in the signs and symptoms of the joint disease and skin manifestations associated with disease. Further improvements in the skin and joint disease were evident at 12 weeks.
Forty-two percent of patients treated with HUMIRA experienced an ACR 20 response after only one dose. ACR (American College of Rheumatology) 20, 50 and 70 criteria represent percent improvement in tender and swollen joint counts and other relevant clinical measures. Also after two weeks, 77 percent of patients experienced at least 25 percent improvement in health-related quality of life as measured by the Health Assessment Questionnaire (HAQ) disability index, which is designed to capture patients' assessment of activities of daily living such as grooming, dressing and walking. Health-related quality of life questionnaires are used to measure the impact of chronic illness on a patient's life.
Further improvement was seen at 12 weeks in both the arthritic symptoms and in health-related quality of life. Sixty-six percent of patients achieved an ACR 20 response and approximately 30 percent attained ACR 50. The HAQ disability index also showed further improvement at week 12 compared to week two.
Substantial improvements also were evident in the skin disease of these patients. Target lesion scores, an evaluation of the severity of a single psoriasis lesion, improved by nearly 30 percent after one dose. After 12 weeks, the target lesion score improved by more than 70 percent.
"The initial results and analysis of this study show that HUMIRA provided significant benefit to many patients with psoriatic arthritis shortly after the first dose," said Christopher T. Ritchlin, M.D., associate professor and lead investigator, University of Rochester, Rochester, New York. "While more research is necessary, these early findings are promising and support HUMIRA's potential as a treatment for psoriatic arthritis."
ABOUT PSORIATIC ARTHRITIS
Psoriatic arthritis is an inflammatory arthritis that is associated with the skin condition psoriasis. It causes inflammation and stiffness in and around the joints, including the knees, wrists, ankles, lower back and neck. Psoriatic arthritis may stem from an autoimmune disorder in which a human protein, tumor necrosis factor-alpha (TNF-???), accumulates in the joints and initiates an inflammatory response that causes swelling and pain.
If left untreated, psoriatic arthritis can be a progressively disabling disease. Epidemiological studies indicate that psoriatic arthritis affects as many as 30 percent of people who have psoriasis, a non-contagious, chronic skin disease characterized by red plaques covered with white scales. Common symptoms of psoriatic arthritis include varying degrees of psoriasis activity along with stiffness, pain, swelling and tenderness of the joints that can lead to a reduced range of motion and potential severe joint destruction.
HUMIRA IMPROVED SYMPTOMS OF ACTIVE ANKYLOSING SPONDYLITIS
To examine the potential therapeutic effects of HUMIRA in patients with non-steroidal anti-inflammatory drug (NSAID)-refractory ankylosing spondylitis (i.e. patients not readily responding to NSAID therapy), researchers studied 10 patients over a 12-week period that received HUMIRA 40 mg every other week. In this open label study, all 10 patients suffered from spinal pain.
HUMIRA treatment induced a positive response in patients after the first dose, with further improvement at the end of the initial 12-week therapy, as measured by Assessment of Ankylosing Spondylitis (ASAS) criteria. ASAS evaluates four primary categories: function, pain, patient's global assessment and inflammation. Scores of ASAS20, ASAS40 and ASAS70 indicate corresponding symptom improvement percentages in at least three of the evaluation categories with no worsening in the remaining category.
The majority of patients in the trial experienced improvement in their symptoms with 70 percent achieving a score of ASAS20, 50 percent reached ASAS40 and 20 percent attained ASAS70.
Also at week 12, 50 percent of the patients experienced 50 percent or greater improvement in scores according to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), a patient-assessed composite index of disease activity measuring pain, stiffness and fatigue.
HUMIRA was well tolerated by patients in the study and no serious infections occurred during the study.
ABOUT ANKYLOSING SPONDYLITIS
Ankylosing spondylitis (AS), or arthritis of the spine, is thought to be an autoimmune disorder in which a human protein has been suggested to play a role in the disease development. As one of the many forms of inflammatory arthritis known as spondyloarthropathies, AS is a chronic disease that primarily affects the spine but can also affect other joints and ligaments, resulting in severe joint and back stiffness and deformity over time.
It is estimated that between 350,000 and one million people in the United States are affected by AS or a related disease and nearly three million in the European community.
Spondyloarthropathies are arthritic in nature, but unlike many other rheumatic conditions, they affect young adults and commonly begin before the age of 35.
ABOUT HUMIRA
HUMIRA is the first human monoclonal antibody available in Europe for RA, and the first tumor necrosis factor alpha (TNF-B) antagonist approved in Europe with an indication for use with methotrexate or as monotherapy. HUMIRA resembles antibodies normally found in the body. It works by blocking TNF-B, a protein that plays a central role in the inflammatory responses of autoimmune diseases such as RA.
Available in many countries, HUMIRA is indicated for the treatment of moderate to severe, active RA in adult patients when the response to disease modifying anti-rheumatic drugs (DMARDs), including methotrexate, has been inadequate.
To ensure maximum efficacy, HUMIRA is given in combination with methotrexate. In Europe, HUMIRA can be given as monotherapy in case of intolerance to methotrexate or when continued treatment with methotrexate is inappropriate. The European Medicines Evaluation Agency (EMEA) issued a positive opinion in April to authorize a label extension for HUMIRA for use in the treatment of adult RA patients for reducing the rate of progression of joint damage and to improve physical function. Such authorizations generally occur approximately 90 days after the issuance of the EMEA opinion.
Abbott received a positive opinion from the EMEA in May 2003 for the treatment of adult RA and was granted European Union approval to market HUMIRA in September 2003. HUMIRA received approval from the U.S. Food and Drug Administration on December 31, 2002. To date, HUMIRA has been approved in 41 countries and launched in 26.
The recommended dose of HUMIRA is 40 mg every other week by subcutaneous injection (a shot beneath the skin). Abbott offers HUMIRA in specially designed pre-filled syringes so patients do not have to mix and measure the medicine or leave their homes for treatment. The pre-filled syringe features handles and a plunger head designed for use by patients whose hands have been affected by their RA.
At the present time, HUMIRA has not received regulatory approval for the treatment of psoriatic arthritis or AS. Clinical trials are currently underway in autoimmune diseases.
IMPORTANT SAFETY INFORMATION
Common adverse events (>1/100 and 1/10 patients.
Patients must be monitored closely for infections, including tuberculosis (TB), before, during and after treatment with HUMIRA. Treatment should not be initiated in patients with active infections until infections are controlled. Patients who develop new infections while using HUMIRA should be monitored closely. HUMIRA should not be used by patients with active TB or other severe infections such as sepsis and opportunistic infections. HUMIRA should be discontinued if a patient develops a new serious infection until infections are controlled. Physicians should exercise caution when considering use of HUMIRA in patients with a history of recurring infection or with underlying conditions that may predispose patients to infections.
TNF-antagonists, including HUMIRA, have been associated in rare cases with exacerbation of clinical symptoms and/or radiographic evidence of demyelinating disease. Prescribers should exercise caution in considering the use of HUMIRA in patients with pre-existing or recent-onset central nervous system demyelinating disorders.
HUMIRA should be used with caution in patients with mild heart failure, and is contraindicated in patients with moderate or severe heart failure. HUMIRA must be discontinued in patients who develop new or worsening symptoms of congestive heart failure.
About Abbott
Abbott Laboratories is a global, broad-based health care company devoted to the discovery, development, manufacture and marketing of pharmaceuticals and medical products, including nutritionals, devices and diagnostics. The company employs more than 55,000 people and markets its products in more than 130 countries.
More information about Abbott Immunology is available at abbottimmunology/.
View drug information on Humira.
Aspirin Reduces Colorectal Cancer Risk In Study Of Patients With Osteoarthritis
A study of Medicare patients with osteoarthritis provides additional evidence that non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin reduce the risk of colorectal cancer. Earlier investigations of the drugs' impact on tumor development could not rule out the possibility that an observed protective effect was caused by other preventive health care measures. The current study, led by a Massachusetts General Hospital (MGH) physician, appears in the August 2007 Journal of General Internal Medicine.
"This is good news for people who take NSAIDs regularly for osteoarthritis," says Elizabeth Lamont, MD, MS, of the MGH Cancer Center, the study's lead author. "Although patients face risks such as bleeding or kidney damage from this therapy, they probably are at a lower risk of developing colorectal cancer." Because of the risks posed by the dosage used to treat osteoarthritis, she and her co-authors stress that currently available NSAIDs should not be used solely to prevent cancer.
Earlier randomized trials clearly showed that NSAID treatment can prevent the development of precancerous colorectal polyps, but whether or not such therapy also reduces the risk of invasive colorectal cancer has not yet been confirmed. Those trials used relatively low doses of aspirin and showed no significant differences in colorectal cancer rates between the aspirin and placebo groups. While many observational studies have shown a protective effect of NSAIDs against colorectal cancer, interpretation of some of those results may have been clouded by other healthy behaviors of the participants.
"It would be ideal to conduct a randomized clinical trial -- in which half the patients receive NSAIDs at doses higher than those used in prior trials and half receive placebos -- and follow both groups for many years for evidence of cancer. But such trials are expensive, time consuming, and could present real health risks to participants. Therefore, we took advantage of a natural 'experiment' by comparing data from patients known to regularly take higher amounts of NSAIDs with that from those taking lower doses in order to evaluate any effect on colorectal cancer risk."
First the researchers reviewed data from the 1993-94 National Ambulatory Medical Care Survey, in which physicians report on the diagnoses of and treatments prescribed to patients seen during a randomly selected week. Those results verified that older patients with osteoarthritis were more than four times as likely to take NSAIDs as were those without osteoarthritis. They then analyzed information from the Survival Epidemiology and End-Results (SEER)-Medicare program, studying groups of elderly Medicare patients with and without colorectal cancer, to search for associations with NSAID use.
Comparing information on 4,600 individuals with colorectal cancer to data from 100,000 controls, they found that a history of osteoarthritis was associated with a 15 percent reduction in the likelihood of a colorectal cancer diagnosis. A similar association was seen when total knee replacement was used as a marker for NSAID treatment.
"The magnitude of colorectal cancer risk reduction between patients with and without osteoarthritis is completely consistent with the risk reduction for pre-cancerous polyps reported in clinical trials of NSAIDs," Lamont says. "Confirming this association supports the need for further research to identify NSAID agents safe enough to be used for regular, preventive therapy by the general population."
Lamont is an assistant professor of Medicine and Health Care Policy at Harvard Medical School. Co-authors of this study, which was supported by a grant from the National Cancer Institute, are Lauren Dias, MD, North Shore Medical Center, and Diane Lauderdale, PhD, University of Chicago.
Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $500 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine. MGH and Brigham and Women's Hospital are founding members of Partners HealthCare HealthCare System, a Boston-based integrated health care delivery system.
Source: Sue McGreevey
Massachusetts General Hospital
"This is good news for people who take NSAIDs regularly for osteoarthritis," says Elizabeth Lamont, MD, MS, of the MGH Cancer Center, the study's lead author. "Although patients face risks such as bleeding or kidney damage from this therapy, they probably are at a lower risk of developing colorectal cancer." Because of the risks posed by the dosage used to treat osteoarthritis, she and her co-authors stress that currently available NSAIDs should not be used solely to prevent cancer.
Earlier randomized trials clearly showed that NSAID treatment can prevent the development of precancerous colorectal polyps, but whether or not such therapy also reduces the risk of invasive colorectal cancer has not yet been confirmed. Those trials used relatively low doses of aspirin and showed no significant differences in colorectal cancer rates between the aspirin and placebo groups. While many observational studies have shown a protective effect of NSAIDs against colorectal cancer, interpretation of some of those results may have been clouded by other healthy behaviors of the participants.
"It would be ideal to conduct a randomized clinical trial -- in which half the patients receive NSAIDs at doses higher than those used in prior trials and half receive placebos -- and follow both groups for many years for evidence of cancer. But such trials are expensive, time consuming, and could present real health risks to participants. Therefore, we took advantage of a natural 'experiment' by comparing data from patients known to regularly take higher amounts of NSAIDs with that from those taking lower doses in order to evaluate any effect on colorectal cancer risk."
First the researchers reviewed data from the 1993-94 National Ambulatory Medical Care Survey, in which physicians report on the diagnoses of and treatments prescribed to patients seen during a randomly selected week. Those results verified that older patients with osteoarthritis were more than four times as likely to take NSAIDs as were those without osteoarthritis. They then analyzed information from the Survival Epidemiology and End-Results (SEER)-Medicare program, studying groups of elderly Medicare patients with and without colorectal cancer, to search for associations with NSAID use.
Comparing information on 4,600 individuals with colorectal cancer to data from 100,000 controls, they found that a history of osteoarthritis was associated with a 15 percent reduction in the likelihood of a colorectal cancer diagnosis. A similar association was seen when total knee replacement was used as a marker for NSAID treatment.
"The magnitude of colorectal cancer risk reduction between patients with and without osteoarthritis is completely consistent with the risk reduction for pre-cancerous polyps reported in clinical trials of NSAIDs," Lamont says. "Confirming this association supports the need for further research to identify NSAID agents safe enough to be used for regular, preventive therapy by the general population."
Lamont is an assistant professor of Medicine and Health Care Policy at Harvard Medical School. Co-authors of this study, which was supported by a grant from the National Cancer Institute, are Lauren Dias, MD, North Shore Medical Center, and Diane Lauderdale, PhD, University of Chicago.
Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $500 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine. MGH and Brigham and Women's Hospital are founding members of Partners HealthCare HealthCare System, a Boston-based integrated health care delivery system.
Source: Sue McGreevey
Massachusetts General Hospital
Small Protein May Have Big Role In Making More Bone And Less Fat
"The pathways are parallel, and the idea is if you can somehow disrupt the fat production pathway, you will get more bone," says Dr. Xingming Shi, bone biologist at the Medical College of Georgia Institute of Molecular Medicine and Genetics.
He's found the short-acting protein GILZ appears to make this desirable shift and wants to better understand how it does it with the long-term goal of targeted therapies for osteoporosis, obesity and maybe more.
"Osteoporosis and obesity are two major public health problems, but people have no idea whether they have a connection," says Dr. Shi. Bone and fat do have a common source: both are derived from mesynchymal stem cells. Bone loss and fat gain also tend to happen with age and with use of the powerful, anti-inflammatory steroid hormones glucocorticoids. "When you age, your bone marrow microenvironment changes; the balance between the bone and fat pathway is broken," says Dr. Shi, a faculty member in the MCG Schools of Medicine and Graduate Studies. "You have more fat cells accumulate."
"The bones of elderly people or those who take glucocorticoids are yellow inside instead of red," he says. And it gets worse: in a classic vicious cycle, the more fat, the more cytokines that stimulate production of bone-destroying osteoclasts and inhibit bone-forming osteoblasts. He recently showed that even the stem cells change with age: their numbers and their ability to differentiate decrease.
Weight gain and bone loss are established side effects of glucocorticoids, whose wide-ranging uses include treatment for arthritis, asthma, infections and organ transplants. Ironically, glucocorticoids also induce a short burst of GILZ. GILZ, in turn, inhibits the transcription factor PPAR??2, called the master regulator of adipogenesis, or fat production, as well as CCAAT/enhancer-binding proteins that turn on this fat-producing gene. One way GILZ does this is by binding to the regulatory region of PPAR??2, Dr. Shi has shown.
To restore a healthier balance of bone and fat production, sustained GILZ action is needed. "When you permanently express GILZ, cells cannot differentiate into fat cells. Instead, you increase bone formation. People like this idea," says Dr. Shi, who has watched the mesynchymal stem cell production shift.
One point of controversy is that, at least in the lab, glucocorticoids seem to enhance bone formation. But Dr. Shi believes it's the short burst of GILZ at work there. He wants to know exactly how it works to see if it could offer a targeted therapy for osteoporosis and obesity and maybe a safer option for many who need glucocorticoids.
A recent $1.5 million, five-year grant from the National Institute of Diabetes and Digestive and Kidney Diseases is enabling Dr. Shi to further test his hypothesis about how GILZ represses PPAR??2 and to see if GILZ over-expression in mice reduces PPAR??2 expression and consequently increases bone and decreases fat. A long-term goal is to understand exactly how PPAR??2 controls fat and bone production.
GILZ also is a powerful immune and inflammation suppressor. It inhibits two key inflammatory molecules, NF-kB and AP-1, which turn on inflammatory genes in response to cytokines, such as TNF-?? and IL-1??, involved in rheumatoid arthritis and other inflammatory diseases, Dr. Shi showed in research published on the cover of the April 15 issue of Journal of Cellular Biochemistry. That study notes GILZ's potential as a novel anti-inflammatory therapy.
In fact, Dr. Shi believes GILZ is a key factor mediating the anti-inflammatory effects of glucocorticoids. A long-acting version of GILZ or a similar substance would be needed to produce, for example, a powerful new arthritis treatment minus the undesirable effects. About 50 percent of arthritis patients who take glucocorticoids develop osteoporosis, he notes, worsening an already difficulty condition worse.
People can't take GILZ now, but another long-term goal is to develop a GILZ-like pill that would dramatically reduce fat production. Dr. Shi already has developed a cell line that continuously expresses GILZ.
Source: Toni Baker
Medical College of Georgia
He's found the short-acting protein GILZ appears to make this desirable shift and wants to better understand how it does it with the long-term goal of targeted therapies for osteoporosis, obesity and maybe more.
"Osteoporosis and obesity are two major public health problems, but people have no idea whether they have a connection," says Dr. Shi. Bone and fat do have a common source: both are derived from mesynchymal stem cells. Bone loss and fat gain also tend to happen with age and with use of the powerful, anti-inflammatory steroid hormones glucocorticoids. "When you age, your bone marrow microenvironment changes; the balance between the bone and fat pathway is broken," says Dr. Shi, a faculty member in the MCG Schools of Medicine and Graduate Studies. "You have more fat cells accumulate."
"The bones of elderly people or those who take glucocorticoids are yellow inside instead of red," he says. And it gets worse: in a classic vicious cycle, the more fat, the more cytokines that stimulate production of bone-destroying osteoclasts and inhibit bone-forming osteoblasts. He recently showed that even the stem cells change with age: their numbers and their ability to differentiate decrease.
Weight gain and bone loss are established side effects of glucocorticoids, whose wide-ranging uses include treatment for arthritis, asthma, infections and organ transplants. Ironically, glucocorticoids also induce a short burst of GILZ. GILZ, in turn, inhibits the transcription factor PPAR??2, called the master regulator of adipogenesis, or fat production, as well as CCAAT/enhancer-binding proteins that turn on this fat-producing gene. One way GILZ does this is by binding to the regulatory region of PPAR??2, Dr. Shi has shown.
To restore a healthier balance of bone and fat production, sustained GILZ action is needed. "When you permanently express GILZ, cells cannot differentiate into fat cells. Instead, you increase bone formation. People like this idea," says Dr. Shi, who has watched the mesynchymal stem cell production shift.
One point of controversy is that, at least in the lab, glucocorticoids seem to enhance bone formation. But Dr. Shi believes it's the short burst of GILZ at work there. He wants to know exactly how it works to see if it could offer a targeted therapy for osteoporosis and obesity and maybe a safer option for many who need glucocorticoids.
A recent $1.5 million, five-year grant from the National Institute of Diabetes and Digestive and Kidney Diseases is enabling Dr. Shi to further test his hypothesis about how GILZ represses PPAR??2 and to see if GILZ over-expression in mice reduces PPAR??2 expression and consequently increases bone and decreases fat. A long-term goal is to understand exactly how PPAR??2 controls fat and bone production.
GILZ also is a powerful immune and inflammation suppressor. It inhibits two key inflammatory molecules, NF-kB and AP-1, which turn on inflammatory genes in response to cytokines, such as TNF-?? and IL-1??, involved in rheumatoid arthritis and other inflammatory diseases, Dr. Shi showed in research published on the cover of the April 15 issue of Journal of Cellular Biochemistry. That study notes GILZ's potential as a novel anti-inflammatory therapy.
In fact, Dr. Shi believes GILZ is a key factor mediating the anti-inflammatory effects of glucocorticoids. A long-acting version of GILZ or a similar substance would be needed to produce, for example, a powerful new arthritis treatment minus the undesirable effects. About 50 percent of arthritis patients who take glucocorticoids develop osteoporosis, he notes, worsening an already difficulty condition worse.
People can't take GILZ now, but another long-term goal is to develop a GILZ-like pill that would dramatically reduce fat production. Dr. Shi already has developed a cell line that continuously expresses GILZ.
Source: Toni Baker
Medical College of Georgia
Ascension Orthopedics Receives FDA Approval For PyroCarbon Foot Implant
Ascension Orthopedics, Inc.
announced today that it has received FDA approval on the first PyroCarbon
implant for the foot. The Ascension(R) PyroSphere(R) implant is designed
for the fourth and fifth tarsometatarsal joints of the foot and is intended
for people suffering from the debilitating effects of arthritis in the
foot.
"We are very pleased that the FDA has approved the PyroSphere(R) for
the lower extremity. We are looking forward to providing the benefits of
our implants to the foot and ankle surgeon," said Robert Martin, CEO of
Ascension Orthopedics.
The Ascension(R) PyroSphere(R) is a revolution in TMT arthroplasty
providing a new option to foot surgeons. The PyroSphere(R) is manufactured
from the patented material, On-X(R) Carbon, which offers characteristics
superior to those of other pyrocarbon material and is available only to
Ascension Orthopedics. The material has shown improved wear qualities
compared to other industry standard materials, thus enhancing the life of
the implant.
The Ascension(R) PyroSphere(R) is the first PyroCarbon implant to be
approved by the FDA in the lower extremity. This approval adds to the many
firsts for Ascension Orthopedics in the extremity market.
"Our goal is to provide our customer, the extremity surgeon, with new
and innovative solutions. Ascension will continue to lead the market in the
development of small joint implants and innovation in extremity surgery,"
adds Robert Martin.
The company has expanded its product platforms to include arthroplasty,
trauma, and tissue regeneration. Ascension currently offers more than ten
arthroplasty products, a complete elbow trauma set, and a tissue
regeneration portfolio that includes a nerve conduit and an adhesion
prevention product. The entry into the foot market for Ascension marks its
continued growth into the upper and lower extremity market.
Ascension Orthopedics, Inc.
ascensionortho
announced today that it has received FDA approval on the first PyroCarbon
implant for the foot. The Ascension(R) PyroSphere(R) implant is designed
for the fourth and fifth tarsometatarsal joints of the foot and is intended
for people suffering from the debilitating effects of arthritis in the
foot.
"We are very pleased that the FDA has approved the PyroSphere(R) for
the lower extremity. We are looking forward to providing the benefits of
our implants to the foot and ankle surgeon," said Robert Martin, CEO of
Ascension Orthopedics.
The Ascension(R) PyroSphere(R) is a revolution in TMT arthroplasty
providing a new option to foot surgeons. The PyroSphere(R) is manufactured
from the patented material, On-X(R) Carbon, which offers characteristics
superior to those of other pyrocarbon material and is available only to
Ascension Orthopedics. The material has shown improved wear qualities
compared to other industry standard materials, thus enhancing the life of
the implant.
The Ascension(R) PyroSphere(R) is the first PyroCarbon implant to be
approved by the FDA in the lower extremity. This approval adds to the many
firsts for Ascension Orthopedics in the extremity market.
"Our goal is to provide our customer, the extremity surgeon, with new
and innovative solutions. Ascension will continue to lead the market in the
development of small joint implants and innovation in extremity surgery,"
adds Robert Martin.
The company has expanded its product platforms to include arthroplasty,
trauma, and tissue regeneration. Ascension currently offers more than ten
arthroplasty products, a complete elbow trauma set, and a tissue
regeneration portfolio that includes a nerve conduit and an adhesion
prevention product. The entry into the foot market for Ascension marks its
continued growth into the upper and lower extremity market.
Ascension Orthopedics, Inc.
ascensionortho
The Boomer Generation And Osteoarthritis
This year, the oldest of the
baby boomers will turn 60. This generation places an emphasis on staying
fit and eating healthy, but boomers can't avoid aging.
Osteoarthritis, the most common form of arthritis, is one of the most
prevalent conditions for this generation. While knee surgery is an option,
alternative and less invasive treatments, like SUPARTZ Joint Fluid Therapy,
are also available.
"Joint fluid therapy can provide relief for debilitating knee pain
without drugs or surgery," said Ken Reali, vice president and general
manager for the Smith & Nephew Clinical Therapies division. "It provides
both doctors and patients with greater options and control over their
treatment of osteoarthritis knee pain."
Osteoarthritis is a slowly progressive degenerative disease in which
the joint cartilage gradually wears away. It afflicts more than 20 million
people nationally and some estimates suggest that as many as 70 million
Americans will suffer from some form of arthritis within the next 20 years.
It strikes not only older people, but also hits people in their 30s and 40s
who have had damage from accidents or sports-related injuries. Without
treatment, the pain associated with osteoarthritis increases over time.
While most physicians agree it should be a last resort, in recent
years, orthopaedic specialists have been reporting increases in knee
replacement surgery. In fact, more than 400,000 procedures are performed
annually and analysts expect that number to continue to increase as the
boomer generation ages.
Because they typically require a hospital stay of several days, knee
replacements are also among the most expensive medical procedures -- the
average hospital bill alone runs over $30,000.
Other less invasive treatments are available and often provide
substantial relief from the pain associated with osteoarthritis of the
knee. Joint fluid therapy is one of the most popular options. This course
of treatment involves injecting a substance called hyaluronan into the
knee. Hyaluronan is a natural substance similar to the fluid found in
particularly high amounts in joint tissues and in the fluid (synovial
fluid) that fills the joints. The body's own hyaluronan acts like a
lubricant and shock absorber in the synovial fluid of a healthy joint.
SUPARTZ Joint Fluid Therapy, marketed in the United States by Smith &
Nephew, is the most prescribed joint fluid therapy in the world, with over
155 million treatments administered. Sidelined by knee pain in 2003, Joan
Reynolds went to her physician for advice. He discovered a meniscus tear in
her right leg and osteoarthritis in both knees. Joan went through a course
of physical therapy, tried over-the-counter pain relief medications and
even the COX II inhibitors Celebrex and Mobic, but her pain persisted.
It was then that Joan's Sports Medicine Specialist, Dr. Peter Vitanzo
Jr. from Philadelphia's Rothman Institute, suggested trying joint fluid
therapy. After a course of treatment with SUPARTZ, she had no discomfort at
all.
Joan was once again enjoying working out at the gym several days a
week, taking walks around her neighborhood and running errands. Without the
constant pain of osteoarthritis consuming her life, Joan is much happier
and gets to spend even more time with her friends and family.
While this form of treatment isn't the best option for everyone, it
provides substantial relief to many who experience nagging osteoarthritic
knee pain. As the baby boomer generation ages, ailments such as
osteoarthritis will become more prevalent. The good news is that medical
advances and a wider array of treatment options are helping to make the
golden years a little brighter and far less painful.
To learn more about osteoarthritis of the knee or joint fluid therapy,
ask your doctor or visit ManageKneePain.
Smith & Nephew Clinical Therapies
ManageKneePain
View drug information on Mobic; Supartz.
baby boomers will turn 60. This generation places an emphasis on staying
fit and eating healthy, but boomers can't avoid aging.
Osteoarthritis, the most common form of arthritis, is one of the most
prevalent conditions for this generation. While knee surgery is an option,
alternative and less invasive treatments, like SUPARTZ Joint Fluid Therapy,
are also available.
"Joint fluid therapy can provide relief for debilitating knee pain
without drugs or surgery," said Ken Reali, vice president and general
manager for the Smith & Nephew Clinical Therapies division. "It provides
both doctors and patients with greater options and control over their
treatment of osteoarthritis knee pain."
Osteoarthritis is a slowly progressive degenerative disease in which
the joint cartilage gradually wears away. It afflicts more than 20 million
people nationally and some estimates suggest that as many as 70 million
Americans will suffer from some form of arthritis within the next 20 years.
It strikes not only older people, but also hits people in their 30s and 40s
who have had damage from accidents or sports-related injuries. Without
treatment, the pain associated with osteoarthritis increases over time.
While most physicians agree it should be a last resort, in recent
years, orthopaedic specialists have been reporting increases in knee
replacement surgery. In fact, more than 400,000 procedures are performed
annually and analysts expect that number to continue to increase as the
boomer generation ages.
Because they typically require a hospital stay of several days, knee
replacements are also among the most expensive medical procedures -- the
average hospital bill alone runs over $30,000.
Other less invasive treatments are available and often provide
substantial relief from the pain associated with osteoarthritis of the
knee. Joint fluid therapy is one of the most popular options. This course
of treatment involves injecting a substance called hyaluronan into the
knee. Hyaluronan is a natural substance similar to the fluid found in
particularly high amounts in joint tissues and in the fluid (synovial
fluid) that fills the joints. The body's own hyaluronan acts like a
lubricant and shock absorber in the synovial fluid of a healthy joint.
SUPARTZ Joint Fluid Therapy, marketed in the United States by Smith &
Nephew, is the most prescribed joint fluid therapy in the world, with over
155 million treatments administered. Sidelined by knee pain in 2003, Joan
Reynolds went to her physician for advice. He discovered a meniscus tear in
her right leg and osteoarthritis in both knees. Joan went through a course
of physical therapy, tried over-the-counter pain relief medications and
even the COX II inhibitors Celebrex and Mobic, but her pain persisted.
It was then that Joan's Sports Medicine Specialist, Dr. Peter Vitanzo
Jr. from Philadelphia's Rothman Institute, suggested trying joint fluid
therapy. After a course of treatment with SUPARTZ, she had no discomfort at
all.
Joan was once again enjoying working out at the gym several days a
week, taking walks around her neighborhood and running errands. Without the
constant pain of osteoarthritis consuming her life, Joan is much happier
and gets to spend even more time with her friends and family.
While this form of treatment isn't the best option for everyone, it
provides substantial relief to many who experience nagging osteoarthritic
knee pain. As the baby boomer generation ages, ailments such as
osteoarthritis will become more prevalent. The good news is that medical
advances and a wider array of treatment options are helping to make the
golden years a little brighter and far less painful.
To learn more about osteoarthritis of the knee or joint fluid therapy,
ask your doctor or visit ManageKneePain.
Smith & Nephew Clinical Therapies
ManageKneePain
View drug information on Mobic; Supartz.
Super-strong Collagen Created By UW-Madison Scientists
A team of University of Wisconsin-Madison researchers has created the strongest form of collagen known to science, a stable alternative to human collagen that could one day be used to treat arthritis and other conditions that result from collagen defects.
"It's by far the most stable collagen ever made," says Ron Raines, a University of Wisconsin-Madison professor of chemistry and biochemistry who led the study, published in the Jan. 12 issue of the Proceedings of the National Academy of Sciences.
Collagen is the most abundant protein in the human body, forming strong sheets and cables that support the structure of skin, internal organs, cartilage and bones, as well as all the connective tissue in between. For decades, doctors have used collagen from cows to treat serious burns and other wounds in humans despite the risk of tissue rejection associated with cross-species transplants.
In 2006, Raines' team figured out how to make human collagen in the lab, creating collagen molecules longer than any found in nature. Now, with funding from the National Institutes of Health, the researchers have taken this line of inquiry one step further, creating a form of super-strong collagen that may one day help millions. Raines says this artificial collagen holds promise as a therapy for conditions such as arthritis, which is caused by a breakdown of the body's natural collagen and affects more than 46 million Americans.
To make the new form of collagen, Raines' team substituted two-thirds of the protein's regular amino acids with less-flexible versions that stiffened the overall structure of the protein and helped it hold its form. "The breakthrough of this approach was the use of rigid analogues that have shapes similar to [the shapes the natural amino acids take] in the folded, functional form of the protein," explains Raines.
The resulting collagen holds together at temperatures far above what it takes for natural collagen to fall apart. And although it's built largely from amino acids that aren't found in nature, X-ray crystallography confirms that the three-dimensional structure of the lab-made collagen is indistinguishable from that of natural collagen, according to UW-Madison bacteriologist Katrina Forest, a co-author of the study.
"This hyper-stable collagen is really a testament to the power of modern protein chemistry," says Raines.
Source:
Ron Raines
University of Wisconsin-Madison
"It's by far the most stable collagen ever made," says Ron Raines, a University of Wisconsin-Madison professor of chemistry and biochemistry who led the study, published in the Jan. 12 issue of the Proceedings of the National Academy of Sciences.
Collagen is the most abundant protein in the human body, forming strong sheets and cables that support the structure of skin, internal organs, cartilage and bones, as well as all the connective tissue in between. For decades, doctors have used collagen from cows to treat serious burns and other wounds in humans despite the risk of tissue rejection associated with cross-species transplants.
In 2006, Raines' team figured out how to make human collagen in the lab, creating collagen molecules longer than any found in nature. Now, with funding from the National Institutes of Health, the researchers have taken this line of inquiry one step further, creating a form of super-strong collagen that may one day help millions. Raines says this artificial collagen holds promise as a therapy for conditions such as arthritis, which is caused by a breakdown of the body's natural collagen and affects more than 46 million Americans.
To make the new form of collagen, Raines' team substituted two-thirds of the protein's regular amino acids with less-flexible versions that stiffened the overall structure of the protein and helped it hold its form. "The breakthrough of this approach was the use of rigid analogues that have shapes similar to [the shapes the natural amino acids take] in the folded, functional form of the protein," explains Raines.
The resulting collagen holds together at temperatures far above what it takes for natural collagen to fall apart. And although it's built largely from amino acids that aren't found in nature, X-ray crystallography confirms that the three-dimensional structure of the lab-made collagen is indistinguishable from that of natural collagen, according to UW-Madison bacteriologist Katrina Forest, a co-author of the study.
"This hyper-stable collagen is really a testament to the power of modern protein chemistry," says Raines.
Source:
Ron Raines
University of Wisconsin-Madison
Gene Responsible For Rheumatoid Arthritis Identified By Manchester Researchers
University of Manchester researchers have identified a genetic variant in a region on chromosome 6 that is associated with rheumatoid arthritis (RA), the most common inflammatory arthritis affecting 387,000 people in the UK.
Professor Jane Worthington and her team at the Arthritis Research Campaign (arc) Epidemiology Unit at the University investigated 9 genetic regions identified earlier this year as potentially harbouring DNA variants determining susceptibility to rheumatoid arthritis. Association to one of the variants on chromosome 6 was unequivocally confirmed, reports this week's Nature Genetics (4 November 2007). Although this variant is not located in a gene, Professor Worthington suggests that it may influence the behaviour of a nearby gene: tumour necrosis factor associated protein (TNFAIP3) as this is a gene that is known to be involved in inflammatory processes.
Rheumatoid arthritis, which affects up to 1% of the adult population, is a chronic inflammatory disease that can affect nearly all joints in the body, particularly the hands and feet. Complications such as lung disease can occur. In addition, patients with RA are more likely to die from cardiovascular disease and some cancers. Some people respond well to treatment, but most suffer a lifetime of disability.
Professor Worthington and her team, who are funded by the medical research charity arc, made their findings as part of the largest ever study of the genetics behind common diseases, the ??9M Wellcome Trust Case Control Consortium (WTCCC). The WTCCC study has given a major boost to the understanding of the genetics of seven common diseases, including RA. As well as providing insights into what leads some people to develop the diseases and offering new avenues for treatments, the success of the approach heralds exciting advances in the study of the genetics of disease.
The Manchester team is currently investigating several genomic regions which may be important in the development of RA but the locus near TNFAIP3 is the first to be fully validated. Until recently, only two other genes were known to explain 50% of genetically determined susceptibility. Now the Manchester researchers are working to understand how the variation within the chromosome 6q region influences the development of RA, the course of the disease and the response to treatment.
Professor Worthington said: "This is a very exciting result; the validation of this association takes us one step closer to understanding the genetic risk factors behind what is a debilitating disease for sufferers and an expensive disease for the NHS.
"We are indebted to the Arthritis Research Campaign (arc) for their longstanding support of this research and for recognizing the importance of establishing large well characterized cohorts of RA patients. This study was made possible by the fantastic collaboration of scientists from five other groups around the UK who helped us to assemble an impressive cohort of over 5,000 samples from RA patients for this experiment. Their continued collaboration will be significant in ensuring the continued progress of this research."
Dr Anne Barton, a clinician on the team, said: "RA is a complex, heterogeneous disease with some people suffering inflammation of the hands and feet which comes and goes whilst others develop a progressive form which can quite rapidly result in marked disability. We believe the genetic marker we have found may determine who develops RA or how severe the disease becomes."
1. The University of Manchester Arthritis Research Campaign (arc) Epidemiology Unit aims to advance understanding of the major rheumatic and musculoskeletal disorders. The unit celebrated its 50th anniversary in 2004, and is one of the world-leading research groups in this field. Around 100 individuals work on a wide variety of different programmes and projects, and the size and strength of the unit permits it to undertake the very large scale, long-term prospective studies which are necessary to truly identify the cause of disease. Recent advances in genetics, molecular biology, biostatistics and computing have had major implications for the types of questions that can be answered using epidemiological methods.
2. The Arthritis Research Campaign (arc) is the fourth largest medical research charity in the UK, raising more than ??30m in 2006/7 entirely from public donations. It currently funds more than 350 research projects into all types of arthritis and musculoskeletal conditions in medical schools and hospitals around the UK, and also has an extensive educational remit. arc.uk/
3. The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical research, in the UK and internationally, spending around ??500 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing. wellcome.ac.uk/ The Wellcome Trust Case Control Consortium (WTCCC) has identified a wealth of genes implicated in coronary heart disease, type 1 and type 2 diabetes, Crohn's disease, bipolar disorder and hypertension, as well as RA. Some of these genes are novel whilst others were known about and have been confirmed by the current study. It has been one of the UK's largest and most successful academic collaborations to date, involving 50 leading research groups and over 200 scientists in the field of human genetics from dozens of institutions. The WTCCC was supported by: the Medical Research Council, British Heart Foundation, Juvenile Diabetes Research Foundation, Diabetes UK, the Arthritis Research Campaign, the National Association for Colitis & Crohn's Disease and MDF The Bipolar Organisation.
Source: Mikaela Sitford
University of Manchester
Professor Jane Worthington and her team at the Arthritis Research Campaign (arc) Epidemiology Unit at the University investigated 9 genetic regions identified earlier this year as potentially harbouring DNA variants determining susceptibility to rheumatoid arthritis. Association to one of the variants on chromosome 6 was unequivocally confirmed, reports this week's Nature Genetics (4 November 2007). Although this variant is not located in a gene, Professor Worthington suggests that it may influence the behaviour of a nearby gene: tumour necrosis factor associated protein (TNFAIP3) as this is a gene that is known to be involved in inflammatory processes.
Rheumatoid arthritis, which affects up to 1% of the adult population, is a chronic inflammatory disease that can affect nearly all joints in the body, particularly the hands and feet. Complications such as lung disease can occur. In addition, patients with RA are more likely to die from cardiovascular disease and some cancers. Some people respond well to treatment, but most suffer a lifetime of disability.
Professor Worthington and her team, who are funded by the medical research charity arc, made their findings as part of the largest ever study of the genetics behind common diseases, the ??9M Wellcome Trust Case Control Consortium (WTCCC). The WTCCC study has given a major boost to the understanding of the genetics of seven common diseases, including RA. As well as providing insights into what leads some people to develop the diseases and offering new avenues for treatments, the success of the approach heralds exciting advances in the study of the genetics of disease.
The Manchester team is currently investigating several genomic regions which may be important in the development of RA but the locus near TNFAIP3 is the first to be fully validated. Until recently, only two other genes were known to explain 50% of genetically determined susceptibility. Now the Manchester researchers are working to understand how the variation within the chromosome 6q region influences the development of RA, the course of the disease and the response to treatment.
Professor Worthington said: "This is a very exciting result; the validation of this association takes us one step closer to understanding the genetic risk factors behind what is a debilitating disease for sufferers and an expensive disease for the NHS.
"We are indebted to the Arthritis Research Campaign (arc) for their longstanding support of this research and for recognizing the importance of establishing large well characterized cohorts of RA patients. This study was made possible by the fantastic collaboration of scientists from five other groups around the UK who helped us to assemble an impressive cohort of over 5,000 samples from RA patients for this experiment. Their continued collaboration will be significant in ensuring the continued progress of this research."
Dr Anne Barton, a clinician on the team, said: "RA is a complex, heterogeneous disease with some people suffering inflammation of the hands and feet which comes and goes whilst others develop a progressive form which can quite rapidly result in marked disability. We believe the genetic marker we have found may determine who develops RA or how severe the disease becomes."
1. The University of Manchester Arthritis Research Campaign (arc) Epidemiology Unit aims to advance understanding of the major rheumatic and musculoskeletal disorders. The unit celebrated its 50th anniversary in 2004, and is one of the world-leading research groups in this field. Around 100 individuals work on a wide variety of different programmes and projects, and the size and strength of the unit permits it to undertake the very large scale, long-term prospective studies which are necessary to truly identify the cause of disease. Recent advances in genetics, molecular biology, biostatistics and computing have had major implications for the types of questions that can be answered using epidemiological methods.
2. The Arthritis Research Campaign (arc) is the fourth largest medical research charity in the UK, raising more than ??30m in 2006/7 entirely from public donations. It currently funds more than 350 research projects into all types of arthritis and musculoskeletal conditions in medical schools and hospitals around the UK, and also has an extensive educational remit. arc.uk/
3. The Wellcome Trust is the largest charity in the UK. It funds innovative biomedical research, in the UK and internationally, spending around ??500 million each year to support the brightest scientists with the best ideas. The Wellcome Trust supports public debate about biomedical research and its impact on health and wellbeing. wellcome.ac.uk/ The Wellcome Trust Case Control Consortium (WTCCC) has identified a wealth of genes implicated in coronary heart disease, type 1 and type 2 diabetes, Crohn's disease, bipolar disorder and hypertension, as well as RA. Some of these genes are novel whilst others were known about and have been confirmed by the current study. It has been one of the UK's largest and most successful academic collaborations to date, involving 50 leading research groups and over 200 scientists in the field of human genetics from dozens of institutions. The WTCCC was supported by: the Medical Research Council, British Heart Foundation, Juvenile Diabetes Research Foundation, Diabetes UK, the Arthritis Research Campaign, the National Association for Colitis & Crohn's Disease and MDF The Bipolar Organisation.
Source: Mikaela Sitford
University of Manchester
Breakthrough Genetic Test Helps Doctors Assess Risk Of Developing Psoriatic Arthritis (PsA)
The first genetic test for Psoriatic arthritis (PsA) is being launched today by PsoriasisDX, LLC, a subsidiary of molecular dermatology research and development innovator PharmaGenoma, Inc. PsA is a progressive irreversible joint disease associated with psoriasis. It is estimated that 20% to 40% of psoriasis patients will eventually develop PsA.
"The PsoriasisDX Genetic Test helps identify those at high risk for developing PsA before they experience arthritic symptoms, providing the opportunity to lessen joint damage through early medical intervention," says Andy Goren, CEO of PharmaGenoma, Inc.
According to University of California, San Francisco (UCSF) Psoriasis expert Dr. John Koo, "Until now, doctors have screened patients after the onset of the inflammatory arthritis. FDA approved medications for the treatment of PsA are most effective at controlling inflammation and arresting joint destruction, but are ineffective at reversing joint damage."
The PsoriasisDX Genetic Test kit ($399) is available through qualified doctors. A genetic sample is collected using a cheek swab, and the sample is mailed for analysis to the PsoriasisDX laboratory. Testing is performed at a CLIA-certified laboratory. Once the genetic analysis is complete, test results will be reported to the doctor.
"Dramatic advances in science mean that genetic tests hold the promise of identifying those at highest risk for developing psoriatic arthritis," says UCSF pharmacogenomics expert Wilson Liao, M.D.
In particular, an immune response gene variant called MICA-A9 is found in approximately 60% of patients who develop PsA. The MICA-A9 association was replicated by four peer-reviewed and published studies involving over 900 patients from multiple ethnic populations.
Positive tests for the MICA-A9 variant result in an approximately 60% chance of developing PsA, while negative tests for the MICA-A9 variant result in an approximately 70% chance of not developing PsA according to Nathan Vandergrift, Ph.D., Assistant Professor of Medicine and Biostatistics at Duke University, and Professor Doron Lancet, PhD, Head of the Crown Human Genome Center at the Department of Molecular Genetics, Weizmann Institute of Science.
Source
PharmaGenoma, Inc.
"The PsoriasisDX Genetic Test helps identify those at high risk for developing PsA before they experience arthritic symptoms, providing the opportunity to lessen joint damage through early medical intervention," says Andy Goren, CEO of PharmaGenoma, Inc.
According to University of California, San Francisco (UCSF) Psoriasis expert Dr. John Koo, "Until now, doctors have screened patients after the onset of the inflammatory arthritis. FDA approved medications for the treatment of PsA are most effective at controlling inflammation and arresting joint destruction, but are ineffective at reversing joint damage."
The PsoriasisDX Genetic Test kit ($399) is available through qualified doctors. A genetic sample is collected using a cheek swab, and the sample is mailed for analysis to the PsoriasisDX laboratory. Testing is performed at a CLIA-certified laboratory. Once the genetic analysis is complete, test results will be reported to the doctor.
"Dramatic advances in science mean that genetic tests hold the promise of identifying those at highest risk for developing psoriatic arthritis," says UCSF pharmacogenomics expert Wilson Liao, M.D.
In particular, an immune response gene variant called MICA-A9 is found in approximately 60% of patients who develop PsA. The MICA-A9 association was replicated by four peer-reviewed and published studies involving over 900 patients from multiple ethnic populations.
Positive tests for the MICA-A9 variant result in an approximately 60% chance of developing PsA, while negative tests for the MICA-A9 variant result in an approximately 70% chance of not developing PsA according to Nathan Vandergrift, Ph.D., Assistant Professor of Medicine and Biostatistics at Duke University, and Professor Doron Lancet, PhD, Head of the Crown Human Genome Center at the Department of Molecular Genetics, Weizmann Institute of Science.
Source
PharmaGenoma, Inc.
Novel DNA Microarray Chip Predicts Functional Impairment And Remission In Rheumatoid Arthritis
A new DNA microarray chip can predict severe disability and remission in patients with rheumatoid arthritis (RA), as presented at EULAR 2008, the Annual Congress of the European League Against Rheumatism in Paris, France. The chip (called the 'ARTchip') has yielded two clinical-genetic models of RA outcomes, to assist physicians in anticipating likely disease progression and prognosis and thereby guide decisions on the best course of treatment for individual patients.
The DNA microarray chip was developed as a tool to study 71 gene polymorphisms (tiny variations in the DNA that can cause or have a role in RA disease activity) in 45 genes chosen specifically for their presumed role in RA.
Dr Alejandro Balsa, of University Hospital La Paz, Madrid, Spain, who led the study, said: "Prognostic markers, identified through our microarray chip, can be used to predict disease outcomes in RA patients which may help healthcare professionals to choose the best treatment for each patient depending on their level of disease activity."
Predicting Severe Disability
6% and 8% of patients in the study and validation populations had a Health Assessment Questionnaire (HAQ) score of 2 or more indicating severe disability due to RA. The results from the DNA array significantly improved the ability of clinical scores to predict functional impairment.
Results of the study showed that clinical scores in combination with the DNA array had a high level of accuracy when compared in the two independent populations (sensitivity (S): 41%, specificity (Sp): 95% and likelihood ratio (LR): 7.6 in the study group, and S: 21%, Sp: 95% and LR: 4.4 in the validation population).
Predicting Remission
Overall, 6% and 7% of patients in the study and validation groups, respectively fell into the disease remission category. The results from the clinical scores in combination with the DNA array also accurately predicted remission in patients with RA, with S: 76%, Sp: 86%, LR: 5.4 compared withand S: 76%, Sp: 75%, LR: 3.1 respectively.
A total of 632 patients fulfilling the American College of Rheumatology (ACR) criteria for RA, with disease onset after 1990 and at least five-year disease duration, were analysed. Baseline variables were recorded including age, gender, smoking, joint counts, acute phase reactants and the presence of anti-CCP antibodies and rheumatoid factor. Remission was defined as absence of joint symptoms without disease-modifying anti-rheumatic drug (DMARD) therapy. Severe disability was defined as an HAQ score of 2 or more. Genetic association analyses were performed with HelixTree. Multivariate logistic regression models and ROC curves, to determine sensitivity, specificity and likelihood ratio, were developed with SPSS software.
Predictive models were initially developed for 375 patients and further validated on 257 RA patients. More than three quarters of the studied cases (77%) were females, and had with 10.9?±3.6 years' disease duration.
A DNA array (or DNA chip) is a technique commonly used in molecular biology where tiny spots of specific DNA are arranged on a solid substance (normally glass). This technique can be used to screen thousands of genes in a single test, for their association with a particular disease or a specific clinical phenotype. In this study, a DNA array was developed and used to identify SNPs that can help to predict the course of RA. Moreover, the study provides rheumatologists with a tool to predict RA aggressiveness, based on a weighted combination of clinical and genetic parameters.
Abstract number: FRI0033
About EULAR
The European League Against Rheumatism (EULAR) is the organisation which represents the patient, health professional and scientific societies of rheumatology of all the European nations.
The aims of EULAR are to reduce the burden of rheumatic diseases on the individual and society and to improve the treatment, prevention and rehabilitation of musculoskeletal diseases. To this end, EULAR fosters excellence in education and research in the field of rheumatology. It promotes the translation of research advances into daily care and fights for the recognition of the needs of people with musculoskeletal diseases by the governing bodies in Europe.
Diseases of bones and joints, such as rheumatoid arthritis and osteoarthritis cause disability in 4 - 5 % of the adult population and are predicted to rise as people live longer.
As new treatments emerge and cellular mechanisms are discovered, EULAR 2008 brings together more than 12,000 experts - scientists, clinicians, healthcare workers, pharmaceutical companies and patients - to share their knowledge in a global endeavour to challenge the pain and disability caused by musculo-skeletal disorders.
To find out more information about the activities of EULAR, visit: eular/
Source: Rory Berrie / Camilla Dormer
European League Against Rheumatism
The DNA microarray chip was developed as a tool to study 71 gene polymorphisms (tiny variations in the DNA that can cause or have a role in RA disease activity) in 45 genes chosen specifically for their presumed role in RA.
Dr Alejandro Balsa, of University Hospital La Paz, Madrid, Spain, who led the study, said: "Prognostic markers, identified through our microarray chip, can be used to predict disease outcomes in RA patients which may help healthcare professionals to choose the best treatment for each patient depending on their level of disease activity."
Predicting Severe Disability
6% and 8% of patients in the study and validation populations had a Health Assessment Questionnaire (HAQ) score of 2 or more indicating severe disability due to RA. The results from the DNA array significantly improved the ability of clinical scores to predict functional impairment.
Results of the study showed that clinical scores in combination with the DNA array had a high level of accuracy when compared in the two independent populations (sensitivity (S): 41%, specificity (Sp): 95% and likelihood ratio (LR): 7.6 in the study group, and S: 21%, Sp: 95% and LR: 4.4 in the validation population).
Predicting Remission
Overall, 6% and 7% of patients in the study and validation groups, respectively fell into the disease remission category. The results from the clinical scores in combination with the DNA array also accurately predicted remission in patients with RA, with S: 76%, Sp: 86%, LR: 5.4 compared withand S: 76%, Sp: 75%, LR: 3.1 respectively.
A total of 632 patients fulfilling the American College of Rheumatology (ACR) criteria for RA, with disease onset after 1990 and at least five-year disease duration, were analysed. Baseline variables were recorded including age, gender, smoking, joint counts, acute phase reactants and the presence of anti-CCP antibodies and rheumatoid factor. Remission was defined as absence of joint symptoms without disease-modifying anti-rheumatic drug (DMARD) therapy. Severe disability was defined as an HAQ score of 2 or more. Genetic association analyses were performed with HelixTree. Multivariate logistic regression models and ROC curves, to determine sensitivity, specificity and likelihood ratio, were developed with SPSS software.
Predictive models were initially developed for 375 patients and further validated on 257 RA patients. More than three quarters of the studied cases (77%) were females, and had with 10.9?±3.6 years' disease duration.
A DNA array (or DNA chip) is a technique commonly used in molecular biology where tiny spots of specific DNA are arranged on a solid substance (normally glass). This technique can be used to screen thousands of genes in a single test, for their association with a particular disease or a specific clinical phenotype. In this study, a DNA array was developed and used to identify SNPs that can help to predict the course of RA. Moreover, the study provides rheumatologists with a tool to predict RA aggressiveness, based on a weighted combination of clinical and genetic parameters.
Abstract number: FRI0033
About EULAR
The European League Against Rheumatism (EULAR) is the organisation which represents the patient, health professional and scientific societies of rheumatology of all the European nations.
The aims of EULAR are to reduce the burden of rheumatic diseases on the individual and society and to improve the treatment, prevention and rehabilitation of musculoskeletal diseases. To this end, EULAR fosters excellence in education and research in the field of rheumatology. It promotes the translation of research advances into daily care and fights for the recognition of the needs of people with musculoskeletal diseases by the governing bodies in Europe.
Diseases of bones and joints, such as rheumatoid arthritis and osteoarthritis cause disability in 4 - 5 % of the adult population and are predicted to rise as people live longer.
As new treatments emerge and cellular mechanisms are discovered, EULAR 2008 brings together more than 12,000 experts - scientists, clinicians, healthcare workers, pharmaceutical companies and patients - to share their knowledge in a global endeavour to challenge the pain and disability caused by musculo-skeletal disorders.
To find out more information about the activities of EULAR, visit: eular/
Source: Rory Berrie / Camilla Dormer
European League Against Rheumatism
In Mouse Model Scientists Find Obesity Alone Does Not Cause Arthritis
The link between obesity and osteoarthritis may be more than just the wear and tear on the skeleton caused by added weight.
A Duke University study has found that the absence of the appetite hormone leptin can determine whether obese mice experience arthritis, no matter how heavy they are.
"We were completely surprised to find that mice that became extremely obese had no arthritis if their bodies didn't have leptin," said Farshid Guilak, Ph.D., director of orthopaedic research in the Duke Department of Surgery. "Although there was some earlier evidence that leptin might be involved in the arthritis disease process, we didn't think that there would be no arthritis at all."
In fact, the joints from the obese mice in the study appearing in the journal Arthritis & Rheumatism looked better than those of the normal control mice, Guilak said. "However, in another study, we found that mice that gained half as much weight on a high-fat diet but processed leptin normally showed significant knee osteoarthritis."
Leptin influences many of the factors involved in osteoarthritis--body weight, inflammation, sex hormone levels, and bone metabolism, said lead author Tim Griffin, Ph.D., who was at Duke Orthopaedic Department and now is an assistant member of the Free Radical Biology and Aging Program at the Oklahoma Medical Research Foundation. "That also makes leptin challenging to study, however, because it's difficult to isolate which pathway is being altered to prevent the development of osteoarthritis."
Leptin is a well-known regulator of appetite, but this is the first time scientists have reported a role for leptin as a metabolic link between obesity and altered cartilage metabolism in joints.
The role of obesity as a risk factor for arthritis is well characterized, but it was thought to be merely a case of overloading joints with extra weight. "It hadn't been studied beyond that," Guilak said. "We knew from other studies that obese people got arthritis in their hands, too, which don't bear weight. This indicated that something besides just body-weight level affected their joints."
The Duke team set out to learn whether the increased body fat of obesity causes an inflammatory response in joints - an imbalance of the immune system signaling proteins called cytokines and other chemicals in osteoarthritis.
They studied mice that were leptin-deficient or deficient in leptin receptors - mice that didn't have any effective leptin in their bodies. Both types of mice overate and gained weight. Then they compared the study mice with normal mice to document knee osteoarthritis. The measurements included pro- and anti-inflammatory cytokines present in arthritis, and several tests to assess bone changes in the knees of the mice.
The knee bones of the leptin-free, obese mice did change, but without forming osteoarthritis. The levels of inflammatory cytokines, which correlate with arthritis, were largely unchanged in these mice. The results suggested that leptin may have a dual role in the development of osteoarthritis by regulating both the skeletal and immune systems.
What does this mean for people? "Obesity is still the number one preventable risk factor of osteoarthritis, but now it seems body fat by itself is not what is causing it," Guilak said. "If you are obese, there are benefits to losing weight in terms of arthritis. For example, if you are obese and lose just 10 pounds, pain decreases significantly. Pain modulation is another clue it might be a chemical or systemic metabolic effect, rather than just a mechanical effect of less weight on the joints."
As with many studies that yield unanticipated findings, "we have a lot of additional questions and experiments that need to be done to further understand how leptin mediates the development of osteoarthritis," Griffin said.
"With obesity and osteoarthritis, there are good similarities between humans and mice," Guilak said. "If we can find a pathway that links a high-fat diet with arthritis, then we can try to identify and block the inflammatory mediators that are linked with the dietary fat."
The study was sponsored by the National Institute for Arthritis, Musculoskeletal and Skin Diseases and the Arthritis Foundation. Lead author Timothy M. Griffin, formerly of the Duke Department of Surgery, is now with the Oklahoma Medical Research Foundation. Co-authors Janet L. Huebner and Virginia B. Kraus are with the Duke Department of Medicine.
Source:
Mary Jane Gore
Duke University Medical Center
A Duke University study has found that the absence of the appetite hormone leptin can determine whether obese mice experience arthritis, no matter how heavy they are.
"We were completely surprised to find that mice that became extremely obese had no arthritis if their bodies didn't have leptin," said Farshid Guilak, Ph.D., director of orthopaedic research in the Duke Department of Surgery. "Although there was some earlier evidence that leptin might be involved in the arthritis disease process, we didn't think that there would be no arthritis at all."
In fact, the joints from the obese mice in the study appearing in the journal Arthritis & Rheumatism looked better than those of the normal control mice, Guilak said. "However, in another study, we found that mice that gained half as much weight on a high-fat diet but processed leptin normally showed significant knee osteoarthritis."
Leptin influences many of the factors involved in osteoarthritis--body weight, inflammation, sex hormone levels, and bone metabolism, said lead author Tim Griffin, Ph.D., who was at Duke Orthopaedic Department and now is an assistant member of the Free Radical Biology and Aging Program at the Oklahoma Medical Research Foundation. "That also makes leptin challenging to study, however, because it's difficult to isolate which pathway is being altered to prevent the development of osteoarthritis."
Leptin is a well-known regulator of appetite, but this is the first time scientists have reported a role for leptin as a metabolic link between obesity and altered cartilage metabolism in joints.
The role of obesity as a risk factor for arthritis is well characterized, but it was thought to be merely a case of overloading joints with extra weight. "It hadn't been studied beyond that," Guilak said. "We knew from other studies that obese people got arthritis in their hands, too, which don't bear weight. This indicated that something besides just body-weight level affected their joints."
The Duke team set out to learn whether the increased body fat of obesity causes an inflammatory response in joints - an imbalance of the immune system signaling proteins called cytokines and other chemicals in osteoarthritis.
They studied mice that were leptin-deficient or deficient in leptin receptors - mice that didn't have any effective leptin in their bodies. Both types of mice overate and gained weight. Then they compared the study mice with normal mice to document knee osteoarthritis. The measurements included pro- and anti-inflammatory cytokines present in arthritis, and several tests to assess bone changes in the knees of the mice.
The knee bones of the leptin-free, obese mice did change, but without forming osteoarthritis. The levels of inflammatory cytokines, which correlate with arthritis, were largely unchanged in these mice. The results suggested that leptin may have a dual role in the development of osteoarthritis by regulating both the skeletal and immune systems.
What does this mean for people? "Obesity is still the number one preventable risk factor of osteoarthritis, but now it seems body fat by itself is not what is causing it," Guilak said. "If you are obese, there are benefits to losing weight in terms of arthritis. For example, if you are obese and lose just 10 pounds, pain decreases significantly. Pain modulation is another clue it might be a chemical or systemic metabolic effect, rather than just a mechanical effect of less weight on the joints."
As with many studies that yield unanticipated findings, "we have a lot of additional questions and experiments that need to be done to further understand how leptin mediates the development of osteoarthritis," Griffin said.
"With obesity and osteoarthritis, there are good similarities between humans and mice," Guilak said. "If we can find a pathway that links a high-fat diet with arthritis, then we can try to identify and block the inflammatory mediators that are linked with the dietary fat."
The study was sponsored by the National Institute for Arthritis, Musculoskeletal and Skin Diseases and the Arthritis Foundation. Lead author Timothy M. Griffin, formerly of the Duke Department of Surgery, is now with the Oklahoma Medical Research Foundation. Co-authors Janet L. Huebner and Virginia B. Kraus are with the Duke Department of Medicine.
Source:
Mary Jane Gore
Duke University Medical Center
Actemra™ Has A Major Impact On Improving Remission Rates In Rheumatoid Arthritis - 3 Studies From The Japanese Phase III Trial Programme
On the 13th November 2006, impressive results will be presented at ACR, the American College of Rheumatology, Washington D. C. These data highlight the outstanding symptom control with Actemra (tocilizumab) monotherapy for patients with rheumatoid arthritis (RA).
The studies showed impressive, consistent remission rates over time, culminating in more than half of patients receiving Actemra achieving remission at 12 months.
Actemra has the potential to become an exciting new therapeutic option for the treatment of RA, a disease with high unmet need where 60-80% of patients do not currently achieve adequate signs and symptoms control.
A Phase III clinical development programme in RA is underway outside of Japan with more than 4,000 patients enrolled in 41 countries including countries in Europe and the USA. Actemra has one of the largest clinical development programmes within Roche.
roche
View drug information on Actemra.
The studies showed impressive, consistent remission rates over time, culminating in more than half of patients receiving Actemra achieving remission at 12 months.
Actemra has the potential to become an exciting new therapeutic option for the treatment of RA, a disease with high unmet need where 60-80% of patients do not currently achieve adequate signs and symptoms control.
A Phase III clinical development programme in RA is underway outside of Japan with more than 4,000 patients enrolled in 41 countries including countries in Europe and the USA. Actemra has one of the largest clinical development programmes within Roche.
roche
View drug information on Actemra.
Mini Stem Cell Lab Formed From Self-Assembled Materials
Imagine having one polymer and one small molecule that instantly assemble into a flexible but strong sac in which you can grow human stem cells, creating a sort of miniature laboratory. And that sac, if used for cell therapy, could cloak the stem cells from the human body's immune system and biodegrade upon arriving at its destination, releasing the stem cells to do their work.
Futuristic" Only in part. A research team from Northwestern University's Institute for BioNanotechnology in Medicine has created such sacs and demonstrated that human stem cells will grow in them. The researchers also report that the sacs can survive for weeks in culture and that their membranes are permeable to proteins. Proteins, even large ones, can travel freely across the membrane.
This new and unexpected mode of self-assembly, to be published March 28 in the journal Science, also can produce thin films whose size and shape can be tailored. The method holds promise for use in cell therapy and other biological applications as well as in the design of electronic devices by self-assembly, such as solar cells, and the design of new materials.
"We started with two molecules of interest, dissolved in water, and brought the two solutions together," said Samuel I. Stupp, Board of Trustees Professor of Materials Science and Engineering, Chemistry and Medicine, who led the research.
"We expected them to mix, but, much to our surprise, they formed a solid membrane instantly on contact. This was an exciting discovery, and we then proceeded to investigate why it happened. Understanding the surprising molecular mechanism was even more exciting."
One of the molecules is a peptide amphiphile (PA), small synthetic molecules that Stupp first developed seven years ago, which have been essential in his work on regenerative medicine. The other molecule is the biopolymer hyaluronic acid (HA), which is readily found in the human body, in places like joints and cartilage. Stupp recently had started a new research project on the regenerative medicine of cartilage, which drew him to hyaluronic acid.
"This is a clear example of informed discovery," said Stupp, director of the Institute for BioNanotechnology in Medicine. "We knew there was something interesting about the interaction between peptide amphiphiles and biopolymers from our previous work on nanostructures that can cause blood vessels to grow. And we were particularly interested in hyaluronic acid because of its role in cartilage, a tissue that adults cannot regenerate and, when damaged in joints, causes grief to humans."
Using just these two molecules, Stupp and his team can make many different structures, the two most important being sacs, which have a solid membrane on the outside and liquid inside, and flat membranes of any shape. The researchers can make the structures large or small, pick up the material with tweezers, stretch it and even easily repair the sacs through self-assembly should the material tear or have some other defect. The sacs also are robust enough to be sutured by surgeons to biological tissues.
The large (hyaluronic acid) and small (peptide amphiphile) molecules come together through supramolecular interactions, not by chemical reaction, in which covalent bonds are formed.
In the case of the flat membrane, the researchers put the peptide amphiphile solution at the bottom of a shallow mold and added on top the hyaluronic acid solution. The two interacted on contact, creating a solid. By varying the mold, the researchers produced a variety of shapes, including stars, triangles and hexagons, each having two chemically different surfaces. When dry, the materials are stiff and strong, like plastic.
In creating a sac, the researchers took advantage of the fact that hyaluronic acid (HA) molecules are larger and heavier than the smaller peptide amphiphile (PA) molecules. In a deep vial, they poured the PA solution and into that poured the HA solution. As the heavier molecules sank, the lighter molecules engulfed them, creating a closed sac with the HA solution trapped inside the membrane.
Having formed the sacs, Stupp and his team next studied human stem cells engulfed by the self-assembly process inside sacs that they placed in culture. The researchers found that the cells remained viable for up to four weeks, that a large protein -- a growth factor important in the signaling of stem cells -- could cross the membrane, and that the stem cells were able to differentiate.
"We expect that genes, siRNAs and antibodies will cross the membranes as well, making this mini cell biology lab a powerful device for research or therapies," said Stupp. "For the development of cancer therapies, we will be able to confine cells within the sacs and study their reaction to different types of therapies as well as to signaling by different cells in neighboring sacs."
In a clever demonstration of self-repair, if the sac's membrane had a hole (from a needle injection, for example), the researchers simply placed a drop of the PA solution on the tear, which interacted with the HA inside, resulting in self-assembly and a sealed hole.
"The membrane is a fascinating and unusual structure with a high degree of hierarchical order," said Stupp. "The membrane grows through a dynamic self-assembly process which generates hybrid nanofibers made up of both molecules and oriented perpendicular to the plane of the membrane. This architecture is very difficult to get spontaneously in materials. Using the right chemistry, the thick membrane structure could be designed to get conduits of charge in solar cells or nanoscale columns of catalytic nanostructures that would extend over arbitrary macroscopic dimensions."
While the underlying, highly ordered structure of the sacs and membranes has dimensions on the nanoscale, the sacs and membranes themselves can be of any dimension and are visible to the naked eye.
The Science paper is titled "Self-Assembly of Large and Small Molecules into Hierarchically Ordered Sacs and Membranes." In addition to Stupp, other authors are Ramille M. Capito (lead author), Yuri S. Velichko and Alvaro Mata, all of Northwestern's Institute for BioNanotechnology in Medicine (IBNAM); and Helena S. Azevedo, of IBNAM and the University of Minho, Portugal.
Source: Megan Fellman
Northwestern University
Futuristic" Only in part. A research team from Northwestern University's Institute for BioNanotechnology in Medicine has created such sacs and demonstrated that human stem cells will grow in them. The researchers also report that the sacs can survive for weeks in culture and that their membranes are permeable to proteins. Proteins, even large ones, can travel freely across the membrane.
This new and unexpected mode of self-assembly, to be published March 28 in the journal Science, also can produce thin films whose size and shape can be tailored. The method holds promise for use in cell therapy and other biological applications as well as in the design of electronic devices by self-assembly, such as solar cells, and the design of new materials.
"We started with two molecules of interest, dissolved in water, and brought the two solutions together," said Samuel I. Stupp, Board of Trustees Professor of Materials Science and Engineering, Chemistry and Medicine, who led the research.
"We expected them to mix, but, much to our surprise, they formed a solid membrane instantly on contact. This was an exciting discovery, and we then proceeded to investigate why it happened. Understanding the surprising molecular mechanism was even more exciting."
One of the molecules is a peptide amphiphile (PA), small synthetic molecules that Stupp first developed seven years ago, which have been essential in his work on regenerative medicine. The other molecule is the biopolymer hyaluronic acid (HA), which is readily found in the human body, in places like joints and cartilage. Stupp recently had started a new research project on the regenerative medicine of cartilage, which drew him to hyaluronic acid.
"This is a clear example of informed discovery," said Stupp, director of the Institute for BioNanotechnology in Medicine. "We knew there was something interesting about the interaction between peptide amphiphiles and biopolymers from our previous work on nanostructures that can cause blood vessels to grow. And we were particularly interested in hyaluronic acid because of its role in cartilage, a tissue that adults cannot regenerate and, when damaged in joints, causes grief to humans."
Using just these two molecules, Stupp and his team can make many different structures, the two most important being sacs, which have a solid membrane on the outside and liquid inside, and flat membranes of any shape. The researchers can make the structures large or small, pick up the material with tweezers, stretch it and even easily repair the sacs through self-assembly should the material tear or have some other defect. The sacs also are robust enough to be sutured by surgeons to biological tissues.
The large (hyaluronic acid) and small (peptide amphiphile) molecules come together through supramolecular interactions, not by chemical reaction, in which covalent bonds are formed.
In the case of the flat membrane, the researchers put the peptide amphiphile solution at the bottom of a shallow mold and added on top the hyaluronic acid solution. The two interacted on contact, creating a solid. By varying the mold, the researchers produced a variety of shapes, including stars, triangles and hexagons, each having two chemically different surfaces. When dry, the materials are stiff and strong, like plastic.
In creating a sac, the researchers took advantage of the fact that hyaluronic acid (HA) molecules are larger and heavier than the smaller peptide amphiphile (PA) molecules. In a deep vial, they poured the PA solution and into that poured the HA solution. As the heavier molecules sank, the lighter molecules engulfed them, creating a closed sac with the HA solution trapped inside the membrane.
Having formed the sacs, Stupp and his team next studied human stem cells engulfed by the self-assembly process inside sacs that they placed in culture. The researchers found that the cells remained viable for up to four weeks, that a large protein -- a growth factor important in the signaling of stem cells -- could cross the membrane, and that the stem cells were able to differentiate.
"We expect that genes, siRNAs and antibodies will cross the membranes as well, making this mini cell biology lab a powerful device for research or therapies," said Stupp. "For the development of cancer therapies, we will be able to confine cells within the sacs and study their reaction to different types of therapies as well as to signaling by different cells in neighboring sacs."
In a clever demonstration of self-repair, if the sac's membrane had a hole (from a needle injection, for example), the researchers simply placed a drop of the PA solution on the tear, which interacted with the HA inside, resulting in self-assembly and a sealed hole.
"The membrane is a fascinating and unusual structure with a high degree of hierarchical order," said Stupp. "The membrane grows through a dynamic self-assembly process which generates hybrid nanofibers made up of both molecules and oriented perpendicular to the plane of the membrane. This architecture is very difficult to get spontaneously in materials. Using the right chemistry, the thick membrane structure could be designed to get conduits of charge in solar cells or nanoscale columns of catalytic nanostructures that would extend over arbitrary macroscopic dimensions."
While the underlying, highly ordered structure of the sacs and membranes has dimensions on the nanoscale, the sacs and membranes themselves can be of any dimension and are visible to the naked eye.
The Science paper is titled "Self-Assembly of Large and Small Molecules into Hierarchically Ordered Sacs and Membranes." In addition to Stupp, other authors are Ramille M. Capito (lead author), Yuri S. Velichko and Alvaro Mata, all of Northwestern's Institute for BioNanotechnology in Medicine (IBNAM); and Helena S. Azevedo, of IBNAM and the University of Minho, Portugal.
Source: Megan Fellman
Northwestern University
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