"ACTEMRA®" Humanized Anti-Human IL-6 Receptor Monoclonal Antibody Conditions For Approval (All Patients Surveillance) Lifted In Japan

Chugai Pharmaceutical Co., Ltd. [Head Office: Chuo-ku, Tokyo; President: Osamu Nagayama (hereafter, "Chugai") announced that it has received a notification from the Japanese Ministry of Health, Labour and Welfare(MHLW) that the conditions for approval (surveillance of all patients1) are lifted with "rheumatoid arthritis(RA)" and "polyarticular-course juvenile idiopathic arthritis (pJIA)" indications for the humanized anti-human IL-6 receptor monoclonal antibody, ACTEMRA®.



For ACTEMRA®, additional approval of indications of "RA (including prevention of structural damage of joints)," "pJIA" and "systemic-onset juvenile idiopathic arthritis (sJIA)" was obtained in April 2008. As one of the conditions for this approval, it had been required that "data on the safety and efficacy of this drug shall be swiftly collected by conducting surveillance of uses in all patients and that the necessary measures shall be taken for the proper use of the drug until data on a certain number of patients is accumulated after marketing."



Data on 3,987 patients with RA and pJIA was submitted to the Japanese MHLW as the interim analysis results of the above surveillance*2. Based on the results, it has been determined that there is no problem necessitating additional measures for the safety and efficacy of this drug at this time. Accordingly, the conditions for approval involving the all patient surveillance have been lifted. For the surveillance, over 10,000 patients have been enrolled up to date. The final analysis of safety data will be done on the 8,300 patients enrolled by November 15, 2009, and will be reported as soon as they become available.



Among the indications of this drug, surveillance of all patients with sJIA and Castleman's disease is still conducted and new patients continue to be enrolled.



ACTEMRA®, the first antibody drug (humanized monoclonal antibody) originating from Japan, was created by Chugai in collaboration with Osaka University, utilizing genetic recombinant technology to produce a monoclonal antibody against the anti-IL6 receptor. It works by inhibiting biological activity of IL-6 through competitively blocking the binding of IL-6 to its receptor.


Rheumatoid arthritis is a systemic inflammatory disease that mainly causes progressive and multiple joint destructions, for which the cause is unknown. It appears more commonly in females in their 40s and 50s, and the disease is causing serious psychological and social problems not only for the patients but also for their families, and measures to counter the disease are seriously needed. Patients are often forced to spend a long time fighting the disease, causing various difficulties in social life such as school life and employment.
















Chugai focuses on bone and joint diseases area as one of the strategic domains, and hopes to contribute to the treatment by providing innovative therapeutic options for patients and medical professionals. The company will continue to make efforts for promoting the proper use and supplying information while giving the highest priority to the safety of patients.


References


1. Objective of surveillance of all patients


For those patients who receive treatment with ACTEMRA®, the data will be evaluated in order to obtain information on the safety (adverse effects of the drug) and efficacy of the drug at an early date and to ensure the safe use of the drug.



2. Result of interim analysis


For the interim analysis, data on 3,987 patients with RA (3,881 patients) and pJIA (106 patients) who were enrolled between April 16, 2008 and July 15, 2009 was evaluated.



Rheumatoid arthritis


-- The incidence of adverse drug reaction was 37.9%, in which the incidence of serious adverse drug reactions accounted for 8.0%. The most frequent adverse drug reactions were "abnormal laboratory test values" and "infections and infestations." The most frequent serious adverse drug reactions were "infections and infestations" including pneumonia. The safety profile was almost the same as in the clinical trials.


-- The efficacy was evaluated using DAS28. Among 2,072 patients whose DAS28 values were collected before the administration of ACTEMRA® and at the 28th week, the high disease activity score of DAS28 (mean?±SD) 5.53?±1.30 before administration markedly improved to 3.00?±1.49 at the 28th week. The remission rate at the 28th week was 45.0%.



Polyarticular-course juvenile idiopathic arthritis (pJIA)


-- The incidence of adverse drug reactions was 41.7%, in which the incidence of serious adverse drug reactions accounted for 10.7%. The most frequent adverse drug reactions were "infections and infestations" same as in the case with RA patients.


-- For the efficacy, the general improvement levels at the 28th week were evaluated, showing "markedly effective" in 54.2%, "effective" in 42.2%, "ineffective" in 2.4%, and "cannot be evaluated" in 1.2%.



The Disease Activity Score (DAS)28 is a combined index that measures disease activity in patients with RA. It combines information from 28 tender and swollen joints (range 0-28), erythrocyte sedimentation rate, and a general health assessment on a visual analog scale. The level of disease activity is interpreted as low (DAS28 < 3.2), moderate (3.2 < DAS28 < 5.1) or high (DAS28 >5.1). DAS28

Impact Sports Increase Bone Strength In Senior Athletes

Running, basketball and other
high-impact sports may lead to stronger bones as people age, according to a
new study presented today at the 74th Annual Meeting of the American
Academy of Orthopaedic Surgeons. Measurements conducted on senior Olympic
athletes found that the bone mineral density (BMD) for those who
participated in impact sports was significantly greater than athletes who
competed in low-impact sports like swimming and cycling.


"While we know that exercise is vital as we get older, this study finds
that the kind of exercise we choose can be just as important," said Vonda
Wright, MD, lead author and assistant professor in the department of
orthopedic surgery at the University of Pittsburgh Medical Center. "The
findings show that a key to maintaining strong, healthy bones as we age is
to engage in impact sports."



The study evaluated 298 athletes competing in the 2005 Senior Olympic
Games in Pittsburgh. The athletes, ages 50 to 93, completed a
health-history questionnaire and underwent ultrasound to measure BMD. The
BMD T-score for athletes in the high-impact group was .4+/-1.3 versus
-1+/-1.4 for athletes in the non-high impact group. After controlling for
age, sex, obesity and osteoporosis medication, participation in high-impact
sports was found to be a significant predictor of BMD.



"The costs associated with caring for people with osteoporosis and
fractures caused by frail bones are rising as the population ages," Dr.
Wright concluded. "Our study implies that persistent participation in
impact sports can positively influence bone health even in the oldest
athletes."



Osteoporosis is a disease of progressive bone loss affecting 28 million
Americans and contributing to an estimated 1.5 million bone fractures per
year. One in two women and one in five men over age 65 will sustain bone
fractures due to osteoporosis.


American Academy of Orthopaedic Surgeons

aaos/

EntreMed Presents Data Demonstrating Antiangiogenic Activity Of 2ME2 In Rheumatoid Arthritis

EntreMed, Inc.
(Nasdaq: ENMD), a clinical-stage pharmaceutical company developing
therapeutics for the treatment of cancer and inflammatory diseases today
announced the presentation of preclinical data for its lead compound, 2-
methoxyestradiol (2ME2), in rheumatoid arthritis (RA). Data were presented
earlier today by EntreMed collaborator, Dr. Ernest Brahn, Professor of
Medicine and Rheumatology Program Director, Division of Rheumatology,
University of California Los Angeles, School of Medicine during an oral
presentation at the Annual European Congress of Rheumatology EULAR 2006
being held this week in Amsterdam, The Netherlands.


Results from studies in a preclinical arthritis model of chronic
autoimmune inflammatory joint disease demonstrated that daily oral
administration of 2ME2 resulted in a statistically significant reduction in
clinical severity of joint inflammation and inhibition of articular joint
damage as determined by blinded high resolution radiographs of bone
erosions. The inhibition of disease progression by 2ME2 treatment was based
on histological analyses of tissue parameters that included inhibition of
(a) white blood cell infiltration; (b) pannus (destruction joint tissue)
severity; and (c) cartilage breakdown.


One of the mechanisms by which 2ME2 exerts DMARD activity in the
preclinical arthritis model involves the inhibition of angiogenesis, which
is necessary to support the growth of the pannus. Further tissue analyses
on the articular joints from 2ME2-treated models demonstrated decreased von
Willebrand factor expression indicating a loss or inhibition of
vascularity. In addition, RT-PCR on dissected synovial tissue showed
suppression in the gene expression of the angiogenic growth factors, VEGF
and FGF-2. These data further support the potential for 2ME2 as a disease
modifying anti-rheumatic drug (DMARD).


Dr. Brahn commented on the results of the study, "These preclinical
data further define the impact of 2ME2 on inflammation and disease
progression and indicate that 2ME2 may represent a novel agent for the
treatment of rheumatoid arthritis. The demonstration that 2ME2 inhibits
angiogenesis in this model of rheumatoid arthritis now establishes a
mechanistic link that leads to the involution of collagen-induced
arthritis."


EntreMed Vice President and Chief Medical Officer, Carolyn F. Sidor,
M.D., M.B.A, commented on the study results, "We continue to generate
positive preclinical data demonstrating the effect of 2ME2 on inflammation
and disease progression in well-accepted preclinical models of rheumatoid
arthritis. Angiogenesis is a needed component of pannus growth in
rheumatoid arthritis, and 2ME2, which has antiangiogenic properties, may
represent a novel oral, non-immunologic DMARD approach to treating this
disease. We will continue to explore 2ME2's DMARD activity in preclinical
rheumatoid arthritis models with the intent of supporting clinical
development in RA in addition to our Phase 2 oncology program."















About Rheumatoid Arthritis


Rheumatoid arthritis affects over 2 million American adults, of which
about two-thirds of them are women. The disease, characterized by pain,
stiffness, swelling, and deformity can become debilitating. Within 5 years
of diagnosis, a third of patients are no longer working, and within 10
years, half of the patients have substantial functional disability. RA can
shorten life expectancy by 5-10 years.


Rheumatoid arthritis (RA), one of the most common forms of arthritis,
is a systemic disease characterized by inflammation of the membrane lining
of the joint, which causes pain, stiffness, redness, swelling, and loss of
function in the joint. The inflamed joint lining, called the synovium,
releases enzymes that destroy bone and cartilage, causing the joint to lose
its shape and alignment. This process can result in joint pain, loss of
movement, and deformity. DMARDs are drugs that have the ability to slow
down disease progression in rheumatoid arthritis and other autoimmune
diseases.


About EntreMed


EntreMed, Inc. (Nasdaq: ENMD) is a clinical-stage pharmaceutical
company developing therapeutic candidates primarily for the treatment of
cancer and inflammation. Panzem(R) (2-methoxyestradiol or 2ME2), the
Company's lead drug candidate, is currently in Phase 2 clinical trials for
cancer, as well as in preclinical development for rheumatoid arthritis.
MKC-1, an oral cell cycle regulator, is in Phase 2 studies for metastatic
breast cancer. ENMD-1198, a novel tubulin binding agent, is also in Phase 1
studies in advanced cancers. EntreMed's goal is to develop and
commercialize new compounds based on the Company's expertise in
angiogenesis, cell cycle regulation and inflammation -- processes vital to
the treatment of cancer and other diseases, such as rheumatoid arthritis.
Additional information about EntreMed is available on the Company's website
at entremed and in various filings with the Securities and
Exchange Commission.


Forward Looking Statements


This release contains forward-looking statements within the meaning of
the Private Securities Litigation Reform Act with respect to the outlook
for expectations for future financial or business performance, strategies,
expectations and goals. Forward-looking statements are subject to numerous
assumptions, risks and uncertainties, which change over time.
Forward-looking statements speak only as of the date they are made, and no
duty to update forward-looking statements is assumed. Actual results could
differ materially from those currently anticipated due to a number of
factors, including those set forth in Securities and Exchange Commission
filings under "Risk Factors," including risks relating to the need for
additional capital and the uncertainty of additional funding; risks
associated with the integration of Miikana and its product candidates; the
early-stage products under development; results in preclinical models are
not necessarily indicative of clinical results, uncertainties relating to
preclinical and clinical trials; success in the clinical development of any
products; dependence on third parties; future capital needs; and risks
relating to the commercialization, if any, of the Company's proposed
products (such as marketing, safety, regulatory, patent, product liability,
supply, competition and other risks).


EntreMed, Inc.

entremed

New Analysis Shows Efficacy Of SIMPONI(TM) (golimumab) In Anti-TNF Experienced Rheumatoid Arthritis Patients

A new analysis demonstrated that a greater proportion of patients with moderately to severely active rheumatoid arthritis (RA) who had prior treatment with anti-tumor necrosis factor (TNF)-alpha agents and received subcutaneous injections of SIMPONI(TM) (golimumab) once every four weeks experienced significant improvements in signs and symptoms through week 24, compared with patients receiving placebo. Patients continued to receive stable doses of methotrexate, sulfasalazine and/or hydroxychloroquine if receiving them at baseline. These data were presented at the 2009 European League Against Rheumatism (EULAR) Annual Congress.


Findings from the GOlimumab After Former anti-TNF Therapy Evaluated in RA (GO-AFTER) study, demonstrated that patients previously treated with adalimumab, etanercept or infliximab responded to and tolerated SIMPONI regardless of the type of prior anti-TNF therapy, as well as the number of prior therapies or reason for discontinuation. According to the study, 39 percent of patients receiving SIMPONI whose prior anti-TNF-alpha therapy had been discontinued due to a lack of efficacy achieved at least a 20 percent improvement in arthritis symptoms (ACR 20) at week 14, compared with 18 percent of patients receiving placebo (p







Investigators reported that the safety profile of SIMPONI among anti-TNF-alpha experienced patients in the GO-AFTER trial was similar to findings from two additional Phase 3 trials that evaluated SIMPONI in biologic-naive patients.


"The efficacy of SIMPONI demonstrated in this Phase 3 study is encouraging news for patients with moderately to severely active rheumatoid arthritis who have been previously treated with anti-TNF agents," said Robert J. Spiegel, MD, chief medical officer, Schering-Plough Research Institute. "The study demonstrates that every four-week subcutaneous injections of golimumab may benefit these patients by reducing the signs and symptoms of rheumatoid arthritis."


About the GO-AFTER Trial


GO-AFTER is the first placebo-controlled, double-blind, Phase 3 registration trial that demonstrates the efficacy and safety of an anti-TNF-alpha agent in patients previously treated with other anti-TNFs. The trial included 461 patients with active RA of 8.65 years mean duration. Discontinuation of previous anti-TNF-alpha therapy was to occur at least 8 to 12 weeks prior to enrollment in the study. Reasons for discontinuation of prior anti-TNF agent included lack of efficacy (58 percent), intolerance (17 percent), and other reasons (40 percent). Patients were randomized to one of three treatment groups: subcutaneous placebo, SIMPONI 50 mg or SIMPONI 100 mg every four weeks. (The approved dose in the US and Canada is 50 mg administered by subcutaneous injection once a month.) At baseline, 66 percent of patients were receiving methotrexate; 5 percent and 8 percent of patients were receiving sulfasalazine and hydroxychloroquine, respectively. Patients continued to receive stable doses of methotrexate, sulfasalazine and/or hydroxychloroquine if receiving them at baseline.


Subgroup analyses were performed for ACR 20 response at week 14 across disease-modifying anti-rheumatic drug use, number of prior anti-TNF-alpha agents and reason for discontinuation of prior TNF inhibitor. Ninety-five percent confidence intervals were calculated comparing the proportions of ACR 20 responders at week 14 in the combined SIMPONI vs. placebo groups. A subset of patients receiving a single prior anti-TNF-alpha agent was also examined to assess the impact of TNF inhibitor types (P75 receptor-fusion protein versus monoclonal antibody) on SIMPONI response.


The occurrence of adverse events (AEs) through week 24 was similar among patients previously receiving only adalimumab (76 percent), etanercept (70 percent) and infliximab (78 percent), as well as among patients who received one, two and three prior anti-TNF-alpha agents in both placebo (74 percent, 77 percent, 71 percent, respectively) and SIMPONI (75 percent, 70 percent, 77 percent respectively) treated patients. SIMPONI was generally well tolerated in this study. Through week 24, 72 percent, 66 percent and 78 percent of patients in the placebo, SIMPONI 50 mg and SIMPONI 100 mg groups, respectively, experienced at least one AE. Seven percent of patients in the placebo group experienced serious AEs, compared with 5 percent and 3 percent of patients in the SIMPONI 50 mg and SIMPONI 100 mg groups, respectively. Serious infections were reported in 3 percent, 3 percent and 1 percent of patients, and injection site reactions (ISR) through week 16 occurred in 3 percent, 4 percent and 11 percent of patients in the placebo, SIMPONI 50 mg and SIMPONI 100 mg groups, respectively. The most commonly reported ISR was erythema. No serious or severe ISRs were reported, and none led to the discontinuation of patients in the study. Antibodies to SIMPONI were detected in 4 percent of golimumab-treated patients (50 mg and 100 mg).


The GO-AFTER study was supported by Centocor Ortho Biotech Inc. and Schering-Plough Corporation.


About Rheumatoid Arthritis


Rheumatoid arthritis (RA) is a chronic and debilitating disease that affects approximately 1.3 million people in the United States and more than three million people in Europe. Signs and symptoms of RA include pain, stiffness and motion restriction in multiple joints. Because RA is a progressive disease, it can cause permanent joint deformity and severe disability if not diagnosed early or if initial treatment is delayed. RA can occur at any age, but is most common in adults 30-50 years old and is two to three times more prevalent in women than in men. The cause of RA is unknown, although genetic factors may contribute to the disease.


About SIMPONI


SIMPONI is a human monoclonal antibody that targets and neutralizes excess TNF-alpha, a protein that when overproduced in the body, due to chronic inflammatory diseases, can cause inflammation in the joints of people with rheumatoid arthritis. The first once-monthly subcutaneous anti-TNF-alpha therapy, SIMPONI is approved in Canada and the United States and is available either through the SIMPONI SmartJect(TM) autoinjector or a prefilled syringe. The approved dose for SIMPONI in the US and Canada is a 50 mg subcutaneous injection given once a month.


Indications in the US:


In the United States, SIMPONI is indicated for the treatment of moderately to severely active rheumatoid arthritis in adults, in combination with methotrexate; active psoriatic arthritis in adults, alone or in combination with methotrexate; and active ankylosing spondylitis in adults.


Indications in Canada:


In Canada, SIMPONI, in combination with methotrexate (MTX), is indicated for reducing the signs and symptoms in adult patients with moderately to severely active RA; reducing signs and symptoms in adult patients with moderately to severely active PsA, alone or in combination with MTX; and reducing signs and symptoms in adult patients with active AS who have had an inadequate response to conventional therapies.


SIMPONI is also being studied as an intravenous infusion therapy for the treatment of moderately to severely active rheumatoid arthritis.


In March 2008, Centocor Ortho Biotech Inc. and Schering-Plough Corporation announced that a Marketing Authorization Application (MAA) had been submitted to the European Medicines Agency (EMEA) requesting the approval of SIMPONI as a once-monthly subcutaneous treatment for adults with RA, PsA and AS.


Centocor Ortho Biotech Inc. developed and discovered SIMPONI and has exclusive marketing rights to the product in the United States. Following regulatory approvals, Schering-Plough will assume exclusive marketing rights outside the United States except in Japan, Indonesia and Taiwan, where SIMPONI will be co-marketed by Mitsubishi Tanabe Pharma Corporation and Janssen Pharmaceutical Kabushiki Kaisha; Hong Kong, where SIMPONI will be exclusively marketed by Janssen-Cilag; and China, where SIMPONI will be exclusively marketed by Xian-Janssen.


Important Safety Information


SIMPONI(TM) is a prescription medicine. SIMPONI(TM) can lower your ability to fight infections. There are reports of serious infections caused by bacteria, fungi, or viruses that have spread throughout the body, including tuberculosis (TB) and histoplasmosis. Some of these infections have been fatal. Your doctor will test you for TB before starting SIMPONI(TM) and will monitor you for signs of TB during treatment. Tell your doctor if you have been in close contact with people with TB. Tell your doctor if you have been in a region (such as the Ohio and Mississippi River Valleys and the Southwest) where certain fungal infections like histoplasmosis or coccidioidomycosis are common.


You should not start SIMPONI(TM) if you have any kind of infection. Tell your doctor if you are prone to or have a history of infections or have diabetes. You should also tell your doctor if you are currently being treated for an infection or if you have or develop any signs of an infection such as:



-- fever, sweat, or chills



-- muscle aches



-- cough



-- shortness of breath



-- blood in phlegm



-- weight loss



-- warm, red, or painful skin or sores on your body



-- diarrhea or stomach pain



-- burning when you urinate or urinate more than normal



-- feel very tired


Tell your doctor about all the medications you take or if you are scheduled to or recently received a vaccine.


Reactivation of hepatitis B virus has been reported in patients who are carriers of this virus and are taking TNF blocker medicines, such as SIMPONI(TM). Some of these cases have been fatal. Your doctor may do blood tests before and after you start treatment with SIMPONI(TM). Tell your doctor if you know or think you may be a carrier of hepatitis B virus or if you experience signs of hepatitis B infection, such as:



-- feel very tired



-- skin or eyes look yellow



-- little or no appetite



-- vomiting



-- muscle aches



-- dark urine



-- clay-colored bowel movements



-- fevers



-- chills



-- stomach discomfort



-- skin rash


If you take SIMPONI(TM) or other TNF blockers, your risk for developing lymphoma or other cancers may increase. You should tell your doctor if you have had or develop lymphoma or other cancers.


Heart failure can occur or get worse in people who use TNF blockers like SIMPONI(TM). Your doctor will monitor you closely if you have heart failure. Tell your doctor right away if you get new or worsening symptoms of heart failure like shortness of breath or swelling of your lower legs or feet.


Rarely, people using TNF blockers can have nervous system problems such as multiple sclerosis. Tell your doctor right away if you have symptoms like vision changes, weakness in your arms or legs, or numbness or tingling in any part of your body.


Liver problems can happen in people using TNF blockers. Contact your doctor immediately if you develop symptoms such as feeling very tired, skin or eyes look yellow, poor appetite or vomiting, or pain on the right side of your stomach.


Low blood counts have been seen with people using TNF blockers. If this occurs, your body may not make enough blood cells to help fight infections or help stop bleeding. Your doctor will check your blood counts before and during treatment. Tell your doctor if you have signs such as fever, bruising, bleeding easily, or paleness.


Rarely, people using TNF blockers have developed lupus-like symptoms. Tell your doctor if you have any symptoms such as a rash on your cheeks or other parts of the body, sensitivity to the sun, new joint or muscle pain, becoming very tired, chest pain or shortness of breath, swelling of the feet, ankles, and/or legs.


Tell your doctor if you are allergic to rubber or latex. The needle cover contains dry natural rubber.


Tell your doctor if you have any symptoms of an allergic reaction while taking SIMPONI(TM) such as hives, swollen face, breathing trouble, or chest pain. Common side effects of SIMPONI(TM) include: upper respiratory tract infection, nausea, abnormal liver tests, redness at site of injection, high blood pressure, bronchitis, dizziness, sinus infection, flu, runny nose, fever, cold sores, numbness or tingling.


About Centocor Ortho Biotech Inc.


Centocor Ortho Biotech Inc. redefines the standard of care in immunology, nephrology, and oncology. The company was created when Ortho Biotech Inc. merged into Centocor, Inc., and Centocor, Inc. was renamed Centocor Ortho Biotech Inc. Built upon a pioneering history, Centocor Ortho Biotech Inc. harnesses innovations in large-molecule and small-molecule research to create important new therapeutic options. Beyond its innovative medicines, Centocor Ortho Biotech is at the forefront of developing education and public policy initiatives to ensure patients and their families, caregivers, advocates, and healthcare professionals have access to the latest treatment information, support services, and quality care.


(This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could vary materially from Centocor Ortho Biotech Inc. and/or Johnson & Johnson's expectations and projections. Risks and uncertainties include general industry conditions and competition; economic conditions, such as interest rate and currency exchange rate fluctuations; technological advances and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approvals; domestic and foreign health care reforms and governmental laws and regulations; and trends toward health care cost containment. A further list and description of these risks, uncertainties and other factors can be found in Exhibit 99 of Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 28, 2008. Copies of this Form 10-K, as well as subsequent filings, are available online at sec, jnj or on request from Johnson & Johnson. Neither Centocor Ortho Biotech Inc. nor Johnson & Johnson undertake to update any forward-looking statements as a result of new information or future events or developments.)


About Schering Plough


Schering-Plough (headquartered in the US) is an innovation-driven, science-centered global health care company. Through its own biopharmaceutical research and collaborations with partners, Schering-Plough creates therapies that help save and improve lives around the world. The company applies its research-and-development platform to human prescription and consumer products as well as to animal health products. Schering-Plough's vision is to "Earn Trust, Every Day" with the doctors, patients, customers and other stakeholders served by its colleagues around the world.


Source: Centocor Ortho Biotech Inc


View drug information on Simponi.

Study Shows RA Patients And Doctors Differ On Disease Severity Assessment

A novel study by researchers at the University of California, San Francisco found that nearly one-third of Rheumatoid Arthritis (RA) patients differed from their physicians in assessment of their disease severity. The disagreement between patient and doctor evaluation of RA activity was most prevalent in patients with depressive symptoms, and those who had poor overall function. Details of the study, the first to examine discordance in an ethnically diverse population, are published in the June issue of Arthritis Care & Research, a journal of the American College of Rheumatology.


According to a 2003 report from the World Health Organization (WHO) the prevalence of RA, an autoimmune disease characterized by painful swelling of the lining of the joints, varies between 0.3% and 1%. In the U.S. experts estimate roughly 1 to 2 million Americans have RA which affects twice as many women than men.


While clinicians who treat patients with diseases such as diabetes or hypertension have a gold standard diagnostic (glucose blood test or blood pressure) to accurately measure disease activity, rheumatologists rely on subjective (patient self-report) and objective measures (physician-assessed joint counts, acute-phase reactants) to determine RA disease activity. An accurate assessment of RA activity is essential in determining the severity of disease, monitoring response to treatment, and is particularly important with the advent of effective, but potentially toxic therapies. Clear patient-physician communication around symptom reporting and assessment of disease activity is central to the management of RA. While prior studies have documented discordance in RA, none have examined the possible association of patient language or mood with discordance, both of which pose barriers to communication.


"The need for patient-provider agreement in disease activity assessment is critical to the safe and effective management of RA," said Jennifer Barton, M.D., from the Department of Medicine, Rheumatology Division, at the University of California, San Francisco, and lead author of the study. The research team recruited 223 participants from the UCSF Rheumatoid Arthritis Cohort, a dual-site observational study, who were consecutively enrolled from the Rheumatoid Arthritis Clinic at San Francisco General Hospital and the UCSF Arthritis Center. Participants had a mean age of 53 (?±14 years) and 88% were women. The ethnic breakdown of the study sample was 45% Latino, 27% Asian/Pacific Islander, 16% Caucasian, 10% African American, 2% American Indian or other.


Researchers gathered clinical data on each subject including rheumatoid factor, sedimentation rate, and tender and swollen joint counts, as well as the patient global assessment of disease severity as measured on a visual analog scale at each visit. Functional status was measured using the Health Assessment Questionnaire (HAQ). The 9-item Patient Health Questionnaire was used to measure depressive symptoms.


"We found clinically meaningful differences between patient and physician assessments of RA disease severity in 36% of cases," confirmed Dr. Barton. "In an overwhelming majority (85%) of these discordant pairs, the physicians' assessments underscored the patients' assessments." Researchers found that the mean VAS score for global disease severity was 46 ?± 26 mm for patients and 31 ?± 21 mm for physicians.


The research team also found that depressive symptoms were common with 30% of participants exhibiting major depression, and these patients had greater odds of discordance with their physicians than those who were not depressed. Researchers noted a lower level of patient-doctor discordance in those patients who had a higher swollen joint count, but discordance persisted in those patients with poorer functional status (HAQ score). "Reducing patient-doctor discordance is an important goal that can improve patient outcomes," concluded Dr. Barton. "Further investigation of the relationships between mood, disease activity, and discordance may help guide interventions that improve RA patient care."


Source: Wiley - Blackwell

New Arthritis Drug Beats Placebo In Phase III Trial

In a randomized trial involving 652 patients with active chronic rheumatoid arthritis (RA) despite treatment, the drug abatacept reduced disease activity, improved physical function and slowed joint damage when compared with placebo (Article, p. 865).



Those receiving abatacept also had more serious infections (2.5 percent vs. 0.9 percent) and infusion reactions.



During the trial, participants continued taking methotrexate, a drug used to aggressively treat RA. The one-year study was limited to patients with established RA (mean duration of about nine years) and who had an inadequate response to methotrexate.



An editorial writer notes that the trial, a so-called "registration trial" needed for FDA approval, compares a new drug to a placebo (sugar pill) rather than to the best alternative drug, which is what would be most useful to practicing clinicians (Editorial, p. 933). The writer also says that practicing clinicians will have to monitor patients receiving abatacept carefully until the drug's safety profile becomes clearer with longer time on treatment.







Tip sheet, Annals of Internal Medicine, April 2006



Contact: Susan Anderson

American College of Physicians

Pfizer Funds $100 Million Study On Cox-2 Inhibitors Celebrex

Pfizer, the makers of Celebrex, a cox-2 inhibitor for people with arthritis, is to fund a $100 million study into the safety of its own drug, Celebrex. The aim of the study is to find out how safe the drug is with arthritis patients who are susceptible to heart attack and stroke.


Dr. Steven Nissen, from the Cleveland Clinic, USA, will lead the study which will involve an estimated 20,000 patients. Dr. Nissen was one of the first critics of cox-2 painkillers. This will be the first large scale trial comparing Cox-2 inhibitors with nonsteroidal anti-inflammatory drugs in patients who are susceptible to heart attack and stroke.


Dr. Nissen said the study was a big gamble for Pfizer, as the results could show that Celebrex is the best drug, or it could turn out to be the worst.


Last year Merck withdrew its drug, Vioxx, from the market because of indications that some patients had increased risk of heart attacks and/or strokes. Then another drug, Bextra (Pfizer) was also withdrawn for the same reason. Since then patients as well as doctors have been in two minds about cox-2 drugs, having to carefully weigh the benefits with the risks. The results of this trial could help these doctors and patients.


In the USA Celebrex is the only Cox-2 Inhibitors left on the market. Sales worldwide have nearly halved over the last twelve months. Nevertheless, Celebrex still managed to bring in $1.26 billion for Pfizer (worldwide sales) during the first nine months of this year alone.


If Celebrex gets the 'all clear' as a result of this study, sales should skyrocket as consumer confidence would increase. Business experts say it is a fair bet - spend $100 million to find out whether your sales could turn into many billions.


Written by:




View drug information on Bextra; Vioxx.

Turmeric Prevents Experimental Rheumatoid Arthritis, Bone Loss, University Of Arizona Study Shows

An ancient spice, long used in traditional Asian medicine, may hold promise for the prevention of both rheumatoid arthritis and osteoporosis, according to a recently completed study at The University of Arizona College of Medicine.



Turmeric, the spice that flavors and gives its yellow color to many curries and other foods, has been used for centuries by practitioners of Ayurvedic medicine to treat inflammatory disorders. Turmeric extract containing the ingredient curcumin is marketed widely in the Western world as a dietary supplement for the treatment and prevention of a variety of disorders, including arthritis.



At the UA College of Medicine, Janet L. Funk, MD, working with Barbara N. Timmermann, PhD, then-director of the National Institutes of Health (NIH)-funded Arizona Center for Phytomedicine Research at the UA, set out to determine whether (and how) turmeric works as an anti-arthritic. They began by preparing their own extracts from the rhizome, or root, of the plant, providing themselves with well-characterized materials to test and to compare with commercially available products. (Dr. Timmermann since has joined the faculty of the University of Kansas, Lawrence, Kan.)



Dr. Funk and her colleagues then tested in animal models a whole extract of turmeric root, only the essential oils, and an oil-depleted extract containing the three major curcuminoids found in the rhizome. Of the three extracts, the one containing the major curcuminoids was most similar in chemical composition to commercially available turmeric dietary supplements. It also was the most effective, completely inhibiting the onset of rheumatoid arthritis.



Dr. Funk, an endocrinologist in the UA Department of Medicine, says this study provides several noteworthy "firsts." Completed with the researchers' own prepared, well-defined extracts, the study represents the first documentation of the chemical composition of a curcumin-containing extract tested in a living organism, in vivo, for anti-arthritic efficacy. It also provides the first evidence of anti-arthritic efficacy of a complex turmeric extract that is analogous in composition to turmeric dietary supplements.



The significance, she explains, is that translating the results of trials such as these to clinical use depends on accurate information about the chemical content and biological activity of the botanical supplements available for use. This work paves the way for the preclinical and clinical trials needed before turmeric supplements can be recommended for medicinal use in preventing or suppressing rheumatoid arthritis.



This study also provides the first in vivo documentation of a mechanism of action - how curcumin-containing extracts protect against arthritis. The researchers found that the curcuminoid extract inhibits a transcription factor called NF-KB from being activated in the joint. A transcription factor is a protein that controls when genes are switched on or off. Once the transcription factor NF-KB is activated, or turned on, it binds to genes and enhances production of inflammatory proteins, destructive to the joint. The finding that curcuminoid extract inhibits activation of NF-KB suggests that turmeric dietary supplements share the same mechanism of action as anti-arthritic pharmaceuticals under development that target NF-KB. It also suggests that turmeric may have a use in other inflammatory disorders, such as asthma, multiple sclerosis and inflammatory bowel disease.
















In addition to preventing joint inflammation, Dr. Funk's study shows that the curcuminoid extract blocked the pathway that affects bone resorption. Noting that bone loss associated with osteoporosis in women typically begins before the onset of menopause, she has begun work on another NIH-funded study to determine whether turmeric taken as a dietary supplement during perimenopause can prevent bone loss and osteoporosis. Both of the studies are supported by the National Center for Complementary and Alternative Medicine (NCCAM) and the Office of Dietary Supplements (ODS), both of the NIH.



An initial publication of the rheumatoid arthritis study results in the Journal of Natural Products, which was among the most-accessed articles from April-June 2006 in this prestigious American Chemical Society journal, is being followed by more detailed study results, which will appear in the November 2006 issue of the American College of Rheumatology flagship journal, Arthritis and Rheumatism. The article, "Efficacy and Mechanism of Action of Turmeric Supplements in the Treatment of Experimental Arthritis," appeared in the online issue of Arthritis and Rheumatism Oct. 30, 2006.







Contributors to the study include Janet L. Funk, MD; Jennifer B. Frye; Janice N. Oyarzo, MS; Nesrin Kuscuoglu, PhD; Jonathan Wilson; Gwen McCaffrey, PhD; Gregory Stafford; Guanjie Chen, MD; R. Clark Lantz, PhD; Shivanand D. Jolad, PhD; Aniko M. So?lyom, PhD; Pawel R. Kiela, DVM, PhD; and Barbara N. Timmermann, PhD.



Contact: Janet Funk, M.D.


University of Arizona Health Sciences Center

ScienceDirect To Host French-Language Journals From Elsevier Masson

Elsevier, a leading publisher of scientific, technical and medical (STM) information, has announced that 45 French-language medical journals from Elsevier Masson will be available on ScienceDirect beginning January 3, 2008.



The titles, including Feuillets de Radiologie, Journal de Chirurgie and La Press M?©dicale, represent a wide range of high-quality journals and complement the 27 ?‰ditions Scientifique et M?©dicales Elsevier (ESME) titles already hosted on the platform. The importance of this content addition is two-fold: it is a response to growing customer demand in French-speaking territories for French-language content, and it furthers Elsevier's local-language publishing program, which is making a wealth of important content accessible globally.



"We are always striving to respond positively to customer requests and deliver the content that will help them in their research," said Jay Katzen, Managing Director, Academic & Government Products. "The addition of this world-class local-language content meets both of these objectives and ensures that ScienceDirect continues to remain a comprehensive and complete platform."



The 45 titles that will be added date from the early 19th and 20th centuries and have strong ties with some of the most revered French Societies including the French Society of Rheumatology, the French Society of Anaesthesiology and the French Society of Pediatrics. The variety of specialist coverage is notable, with journal subjects ranging from anaesthesiology to pharmacology.



All of the journals to be added consist of high-quality articles, reviews and case reports. In addition, a number of the journals include some abstracts and articles in English. Subscribers will benefit from the current (2008) articles as well as four years in backfiles.



The Elsevier Masson collection on ScienceDirect will evolve with new titles added each year through new launches and acquisitions. For more information on ScienceDirect and for a complete list of titles that will be added, please visit info.sciencedirect/.







About ScienceDirect



Over a quarter of the world's full text scientific, technical and medical (STM) articles - managed by renowned editors, written by respected authors and read by researchers from around the globe - are available in one place: ScienceDirect (sciencedirect).



Elsevier's extensive and unique full-text collection covers authoritative titles from the core scientific literature including high impact factor titles such as THE LANCET, Cell and Tetrahedron. Over eight million articles are available online, including Articles in Press which offer rapid access to recently accepted manuscripts. The critical mass of information available on ScienceDirect is unsurpassed. Coverage includes over 2,000 journals published by Elsevier and dynamic linking to journals from approximately 2,000 STM publishers through CrossRef. An expanding program of online major reference works, handbooks, book series and eBooks in all fields of science seamlessly interlinks with primary research referenced in journal articles.
















About Elsevier



Elsevier is a world-leading publisher of scientific, technical and medical information products and services. Working in partnership with the global science and health communities, Elsevier's 7,000 employees in over 70 offices worldwide publish more than 2,000 journals and 1,900 new books per year, in addition to offering a suite of innovative electronic products, such as ScienceDirect (sciencedirect/), MD Consult (mdconsult/), Scopus (info.scopus/), bibliographic databases, and online reference works.



Elsevier (elsevier/) is a global business headquartered in Amsterdam, The Netherlands and has offices worldwide. Elsevier is part of Reed Elsevier Group plc (reedelsevier/), a world-leading publisher and information provider. Operating in the science and medical, legal, education and business-to-business sectors, Reed Elsevier provides high-quality and flexible information solutions to users, with increasing emphasis on the Internet as a means of delivery. Reed Elsevier's ticker symbols are REN (Euronext Amsterdam), REL (London Stock Exchange), RUK and ENL (New York Stock Exchange).



Source: Lauren Hillman

elsevier/
Elsevier

Prexige, Anti-inflammatory Drug, Withdrawn In Canada

The sale of Prexige (lumiracoxib) has been stopped in Canada. Health Canada advises that it will cancel the medication's market authorization because of potential for serious liver-related adverse events.


Prexige is a Cox-2 selective inhibitor non-steroidal anti-inflammatory drug. It has been on the market in Canada since November 2006. The drug is used for treating adult patients with the signs and symptoms of osteoarthritis - maximum dose 100 mg (daily).


After Canadian authorities reviewed additional safety information submitted by Novartis Pharmaceuticals Canada, Inc., it was decided to withdraw authorization for Prexige. The additional information was sought soon after the same drug was pulled from the Australian market this year, due to reports of serious liver adverse events that were associated with the drug at doses of 200mg and 400mg per day.


Health Canada concluded, after reviewing the additional safety information, that it is not possible to safely manage the risk of liver-related adverse events with daily doses of 100mg.


Two cases of liver-related adverse events linked to Prexige use have been reported to Canadian authorities since the drug's approval. Four cases have been reported worldwide for daily doses of 100mg.


Health Canada urges patients who are currently taking Prexige to contact their health care provider and discuss other treatment options. Do not dispose of the product yourself, asks Health Canada - return it to your pharmacy to ensure appropriate disposal.


-- Health Canada

-- prexige


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