New Evidence Shows Rituximab Halts Damage To Joints

New data, presented today at the Annual European Congress of Rheumatology show for the first time that a rheumatoid arthritis (RA) treatment, rituximab, is able to significantly inhibit the structural damage to joints caused by RA in patients who have long-standing disease and an inadequate response to one or more TNF (Tumour Necrosis Factor) inhibitors.



Prevention of joint structural damage in rheumatoid arthritis is a critical therapeutic outcome. Many patients respond well to the TNF inhibitors, a relatively new class of therapy which prevents TNF protein causing inflammation in rheumatoid arthritis, however approximately 30% - 40% of patients treated with this therapy experience either an inadequate response or are intolerant to such therapies. As such, the study was designed to investigate the effect at 1 year of rituximab (a new therapy targeting B-cells - cells which create abnormal antibodies causing rheumatoid arthritis symptoms) plus methotrexate (an antimetabolite drug which inhibits the synthesis of DNA, RNA and protein, previously the gold standard in the treatment of rheumatoid arthritis) on joint structural damage, compared to methotrexate alone in rheumatoid patients with inadequate response to one or more TNF inhibitors.



The results reveal bone erosions in patients in the rituximab group were reduced by over half during the course of a year compared to patients receiving placebo (erosion scores of 0.59 and 1.32 respectively), as were the narrowing of joint spaces (scores of 0.41 and 0.99 respectively). In addition the proportion of patients with no change in erosion score was significantly higher in the rituximab group compared to placebo.



"These findings suggest that treatment with rituximab plus methotrexate is associated with significant inhibition of joint structural damage, an important finding in patients who do not currently respond to other treatments" explained Professor Edward Keystone, Rheumatology Department at the University of Toronto, Canada, one of the studies principle investigators. "Stopping joint damage indicates that the disease pathway has been interrupted, a goal we strive for in the treatment of rheumatoid arthritis. As such, today's results have the potential to offer many patients a new hope".







Jim Baxter - Onsite tel: +44 (0) 7900 605652

Jo Spadaccino - Onsite tel: +44 (0) 7773 271930

Mia Gannedahl - Office tel: +44 (0) 20 7331 2325



Abstract number: OP0016



About EULAR



* The European League Against Rheumatism (EULAR) is the organization 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, the 7th Annual European Congress of Rheumatology in Amsterdam (EULAR 2006) brings together more than 10,000 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/.



Contact: Mia Gannedahl

European League Against Rheumatism

Treating Gum Disease Helps Rheumatoid Arthritis Sufferers

Not yet convinced about keeping your healthy teeth, here's another reason.


People, who suffer from gum disease and also have a severe form of rheumatoid arthritis, reduced their arthritic pain, number of swollen joints and the degree of morning stiffness when they cured their dental problems. Researchers from the Case Western Reserve University School of Dental Medicine and University Hospitals of Cleveland reported on this new intervention for arthritis in the Journal of Periodontology.


"It was exciting to find that if we eliminated the infection and inflammation in the gums, then patients with a severe kind of active rheumatoid arthritis reported improvement on the signs and symptoms of that disease," said Nabil Bissada, D.D.S., chair of the department of periodontics at the dental school.


"It gives us a new intervention," adds Bissada.


This is not the first time that gum disease and rheumatoid arthritis have been linked. According to another researcher in the study, Ali Askari, M.D., chair of the department of rheumatology at University Hospitals, "From way back, rheumatologists and other clinicians have been perplexed by the myth that gum disease may have a big role in causing systematic disease."


He added that historically teeth were pulled or antibiotics given for treatment of rheumatoid arthritis, which actually treated the periodontitis. The patients got better.


Askari and Bissada are part of a team of researchers that studied 40 patients with moderate to severe periodontal disease and a severe form of rheumatoid arthritis.


The study results should prompt rheumatologists to encourage their patients to be aware of the link between periodontal disease and rheumatoid arthritis, says Askari.


Bissada notes that gum disease tends to be prevalent in rheumatoid arthritis patients.


Both inflammatory diseases share similarities in the progression of the disease over time. In both diseases, the soft and hard tissues are destroyed from inflammation caused by toxins from bacterial infection.


One toxin from the inflamed areas called tumor neurosis factor-alpha (TNF-?±) is a marker present in the blood when inflammation is present in the body. TNF-?± can initiate new infections or aggravate sites where inflammation already exists.


The study's participants were divided into four groups. Two groups of patients were receiving a new group of anti-TNF-?± drugs that block the production of TNF-?± at inflamed rheumatoid arthritis sites. Two groups were not on this new medication. Half of group of the participant on the medication and half not receiving the new drug received a standard nonsurgical form of periodontal treatment to clean and remove the infection from the bones and tissues in the gum areas. The other half of those studied did not receive the treatment until after completion of the study.















After receiving treatment for the gum disease, improvement in rheumatoid arthritis symptoms was seen in patients who did and did not receive the anti-TNF-?± medications, which block the production of TNF-?± that aggravate or can cause inflammation. Patients on the TNF- ?± inhibitors showed even greater improvements over those not receiving the drugs.


"I'm optimistic that someday the biologic agents that we use successfully in treatment of rheumatoid arthritis will lead to improvement of periodontitis and would be available for use and treatment of this perplexing problem," says Askari.


"Again we are seeing another link where good oral health improves the overall health of an individual," says Bissada, who adds that studies have linked gum disease to premature births, heart disease and diabetes.


Other researchers contributing to findings in the article, "Periodontal Therapy Reduces the Severity of Active Rheumatoid Arthritis in Patients Treated with or Without Tumor Necrosis Factor Inhibitors," were P. Ortiz, Yiping Han, Leena Palomo, and Ashok Panneerselvam from Case Western Reserve University; and M.S. Al-Zahrani from King Abdulaziz University.


Case Western Reserve University is among the nation's leading research institutions. Founded in 1826 and shaped by the unique merger of the Case Institute of Technology and Western Reserve University, Case Western Reserve is distinguished by its strengths in education, research, service, and experiential learning. Located in Cleveland, Case Western Reserve offers nationally recognized programs in the Arts and Sciences, Dental Medicine, Engineering, Law, Management, Medicine, Nursing, and Social Work.


Source: Case Western Reserve University

Rigel Announces Initiation Of Phase 1 Clinical Trial Of R348 For Rheumatoid Arthritis, Psoriasis And Other Immune Disorders

Rigel
Pharmaceuticals, Inc. (Nasdaq: RIGL) announced that it has begun
enrolling patients in a Phase 1 study to evaluate the safety and
tolerability of R348, an orally available, potent inhibitor of Janus Kinase
3 (JAK3), as a potential treatment for patients with rheumatoid arthritis
(RA), psoriasis and other immune disorders. In preclinical studies, R348
was shown to be effective in reducing arthritic symptoms, bone destruction
and swelling. It has also shown efficacy in models of psoriasis and
transplant rejection. This is Rigel's fourth novel product candidate in
clinical trials.


"R348 enters the clinic at a time when Rigel's product portfolio is
demonstrating its potential contribution to the field of immunology," said
Donald G. Payan, M.D., executive vice president and chief scientific
officer at Rigel. "With R348 targeting T-cells and our oral syk kinase
inhibitor, R788, targeting B-cells and other immune cells, Rigel has
mounted a comprehensive assault on autoimmune disorders," he added.



This study will evaluate the safety and pharmacokinetics of R348 in
young, healthy males using a double blind, placebo controlled, single dose
and multiple rising doses of R348. Results are expected in mid-2008.



JAK3 in RA and Other Immune Disorders



RA affects approximately 1% of the population worldwide --
approximately 2.1 million Americans -- and is a debilitating and
degenerative autoimmune disease. Psoriasis affects approximately 7.5
million in the U.S. and an estimated 125 million worldwide, and is a
lifelong skin disease. About 10-30% of patients with psoriasis also develop
psoriatic arthritis, which causes pain, swelling and stiffness of the
joints. These diseases are mediated by activated T-cells, which rely on
JAK3 signaling.



Current treatments for these diseases include steroids, methotrexate
and various injectable biologic agents. Rigel's product candidate, R348, is
believed to be orally bio-available and may provide an attractive
alternative or supplement to currently used agents.



R348 is also being studied as a potential treatment for transplant
rejection and graft vs. host disease.



About Rigel



Rigel is a clinical-stage drug development company that discovers and
develops novel, small-molecule drugs for the treatment of
inflammatory/autoimmune diseases and cancer, as well as viral and metabolic
diseases. Our goal is to file one new investigational new drug (IND)
application in a significant indication each year. Rigel has achieved this
goal every year since 2002. Our pioneering research focuses on
intracellular signaling pathways and related targets that are critical to
disease mechanisms. Rigel's productivity has resulted in strategic
collaborations with large pharmaceutical partners to develop and market our
product candidates. Rigel has product development programs in
inflammatory/autoimmune diseases such as rheumatoid arthritis,
thrombocytopenia and asthma, as well as in cancer.



This press release contains "forward-looking" statements, including
statements related to the potential efficacy and commercial potential of
R348 and Rigel's plans to pursue further clinical development thereof. Any
statements contained in this press release that are not statements of
historical fact may be deemed to be forward-looking statements. Words such
as "believes," "plans," "potential," and similar expressions are intended
to identify these forward-looking statements. There are a number of
important factors that could cause Rigel's results to differ materially
from those indicated by these forward-looking statements, including risks
associated with the timing and success of clinical trials and the
commercialization of product candidates, potential problems that may arise
in the clinical testing and approval process and Rigel's need for
additional capital, as well as other risks detailed from time to time in
Rigel's SEC reports, including its Form 10-Q for the quarter ended
September 30, 2007. Rigel does not undertake any obligation to update
forward-looking statements.


Rigel Pharmaceuticals, Inc.

rigel

ArGentis Acquires Rights To Rheumatoid Arthritis Therapy Entering Phase I Clinical Trial

arGentis Pharmaceuticals, LLC announced that it will collaborate with the University of Tennessee Health Science Center (UTHSC) and the Veterans Affairs Medical Center of Memphis (VAMC) to initiate the first human clinical evaluation of an oral altered peptide ligand (APL), ARG301, in a Phase I study of Rheumatoid Arthritis patients. ARG301 is a synthetic peptide, which in animal studies appears to down regulate autoimmunity to Type II collagen (CII), a known autoantigen in RA. Investigators at the UTHSC and Memphis VAMC developed the therapy and have received a Clinical Merit Review Grant from the Department of Veterans Affairs to conduct the trial.


"Due to its unique mechanism of action and compelling preclinical data, we are hopeful that ARG301 will offer a novel therapeutic approach for rheumatoid arthritis," said Tom I. Davis, II, Chief Executive Officer of arGentis. "In continuing our partnership with UTHSC and University of Tennessee Research Foundation, arGentis is very pleased to add this promising oral therapeutic consistent with our autoimmunity R&D approach."


Research in animal models suggests APLs (Altered Peptide Ligands) are effective in preventing and ameliorating tissue-specific autoimmune diseases. Trials of APLs administered intravenously or subcutaneously in human autoimmune disease have had mixed results. None of these trials, however, incorporated a pre-selection step to test the ability in vitro of the APL, to down regulate Th1 response by patient's peripheral blood mononuclear cells (PBMC) stimulated by a disease-specific autoantigen such as CII in RA patients.


In preclinical testing, mice susceptible to Collagen Induced Arthritis (CIA) bear a transgene for the human RA MHC susceptibility genes, DR1 or DR4. These mice appear to be resistant to CIA after oral administration of ARG301. Although the precise mechanism by which the specific peptide comprising ARG301 exerts its effect is not yet clear, the interaction of the APL/MHC complex with the TCR appears to play a key role in influencing the differentiation of naive T cells into effector cells.


Based on the experience in animals, oral administration of APLs to preselected "in vitro" responders should provide a nontoxic and highly defined therapy for humans with tissue-specific autoimmune diseases such as RA.


42 RA patients will be enrolled a Phase I Trial at the Memphis VAMC which will evaluate multiple ascending doses of ARG301 to be administered orally. The primary objectives of the trial will be to determine if one or more of the three doses of ARG301 given to Rheumatoid Arthritis patients will generate functional T regulatory cells and decrease immune reactivity to CII. The study will have 3 ARG301 treatment arms, each with 10 patients and a placebo arm of 12 patients. Patients will be enrolled who have demonstrated T cell immunity to CII and have an in vitro response to ARG301 at the screening visit. Patients will be randomized to one of the 4 arms, and each of the 3 ARG301 and placebo treatments will be given for 16 weeks.















About ARG301


The altered peptide ligand ARG301 is an oligopeptide derived from human CII sequence with substituted amino acids that binds to the MHC class II and interacts with the T cell receptor. ARG301 acts to change the cytokine profile from Th1 to Th2. Preclinically, DR1 or DR4 transgenic mice treated with oral or parenterally administered ARG301 were protected from arthritis induced by CII immunization. Short term toxicity studies using 100x the maximal human dose of ARG301 on a weight basis in mice did not cause any detectable toxicity. ARG301 is anticipated to have an exceptionally good safety profile in the clinic. To prove concept, ARG301 will eventually be evaluated in a broader trial of Rheumatoid Arthritis patients.


About Rheumatoid Arthritis


Rheumatoid Arthritis (RA) is an autoimmune disease that causes chronic inflammation of the joints and is the most common form of inflammatory arthritis. RA most often affects the smaller joints, such as those of the hands and/or feet, wrists, elbows, knees, and/or ankles. The cause of RA is not known but usually develops between 30 and 50 years of age. Although there is no cure for RA, the disease can be controlled in most people. Early, aggressive therapy to stop or slow down inflammation in the joints can prevent or reduce symptoms, joint destruction and deformity.


RA has a significant impact on both individual lives and society, including:


- According to the Centers for Disease Control and Prevention (CDC), arthritis and other rheumatic conditions are the leading cause of disability in the U.S.,

- 3 million RA sufferers in the U.S.,

- 2.2 million are women,

- U.S. incidence expected to increase to 5.8 million in the U.S. by 2013,

- According to Johns Hopkins, disability is higher among patients with rheumatoid arthritis, with 60 percent being unable to work 10 years after disease onset,

- People with rheumatoid arthritis have an increased risk of mortality or death rate compared to the general population, living 10-15 years less than healthy counterparts.


About Veterans Affairs Medical Center


The Department of Veterans Affairs Medical Center is affiliated with the University of Tennessee Health Science Center. Since 1922, the Memphis VAMC has been improving the health of the men and women who have so proudly served our nation with services available to more than 196,000 veterans living in a 53-county area of western Tennessee, northern Mississippi and northwest Arkansas.


Source

arGentis Pharmaceuticals

Arthritis Care Chief Executive Appointed As 'Patient And Public Champion', UK

The first 'Patient and Public Champion' to monitor NHS efforts to reach the Government's target of reducing waiting times to 18 weeks has been announced by health minister, Andy Burnham.



Neil Betteridge, chief executive of Arthritis Care will take up the appointment from today (4 May 2007). He will work closely with ministers and the NHS to ensure that patients are at the centre of the 18 week pledge. Mr Betteridge will highlight their needs as reforms to meet the target are implemented across England. He will also consult with patients and the public, and encourage them to influence the reforms locally.



The Government has pledged that, by a deadline of December 2008, all patients can expect to start their treatment within 18 weeks of referral.



Announcing the appointment, the health minister said:



"Our commitment to improving the NHS means that by 2008 all patients will be assured of faster treatment. Not simply another target, 18 weeks captures the whole patient journey - from referral to start of treatment - with many patients seen even more quickly than that.



"This will be a major achievement for the NHS, making it more streamlined and productive as well as leading to a much better experience for patients - and helps change people's lives by improving care and cutting unnecessary delays.



"I'm delighted to appoint Neil Betteridge as patient champion for this important policy. He has an outstanding track record of speaking up for patients and his appointment underlines how we want the NHS transformed into a truly patient led service."



Mr Betteridge said:



"I'm delighted to be asked to take up this important role on behalf of all patients. This is a once in a lifetime opportunity for patients and the public to help shape the future delivery of services.



As the NHS changes, it is crucial that patients are right at the heart of any improvements. My role will be to keep the focus on people not just the target.



Currently many people with long term conditions, such as arthritis, are in long queues and the wrong queues. For the first time in nearly 60 years, this initiative will perhaps bring an end to waiting in the NHS" said Mr Betteridge.



Neil Betteridge biography



Neil developed rheumatoid arthritis at the age of 3, which had a major impact on his life for the next ten years or so and continues to inform all his work.



Growing up in Nuneaton, Warwickshire, Neil battled through years of intensive physiotherapy and hydrotherapy and was one of the lucky few with severe arthritis to regain much of his mobility. He progressed from being a wheelchair user at age 6 to being appointed captain of the school football team at age 11.



Neil studied and taught at Liverpool University for most of the 1980s. Whilst completing his M Phil on the work of T. S. Eliot he became a trustee at Toxteth Victim Support and subsequently took up a paid position with Liverpool Children's Holiday Organisation. Within one year he was made Director of the organisation.



Following a brief spell teaching in Italy, Neil has since worked as a public policy specialist and campaigner on arthritis and pan-disability issues.



Formerly Head of Public Policy and Campaigning at RADAR (Royal Association of Disability and Rehabilitation), he is now Chief Executive at Arthritis Care. He is additionally Chair of ARMA, the umbrella group for arthritis in the UK and it lead for all of their lobbying work for the EU and European Parliament; Chair of the UK government's Disabled Persons Transport Advisory Committee (DPTAC); and a member of the Commission for Integrated Transport.


He was, until recently, Chair of the PARE Manifesto, the European campaigns network of arthritis patient groups and he has recently completed 4 years as Vice President of EULAR (European League Against Rheumatism) as well as a 3 year term of office as a trustee with the Long Term Medical Conditions Alliance.



Throughout 2004 and 2005 Neil served as a 'patient advisor' on the steering group of the Department for Health-sponsored Musculoskeletal Services Framework.



arthritiscare.uk

New Research Shows Exercise Prevents Arthritis Symptoms In Women

Women in their 70s who keep active could be dodging painful arthritis symptoms, according to research published today in Arthritis Research & Therapy. The study is the first to show that the more you exercise, the better your chances of preventing the onset of stiff and painful joints.



Kristiann Heesch and colleagues at the University of Queensland, Australia examined data on middle-aged (48-55) and older (72-79) women collected using surveys over three years as part of the Australian Longitudinal Study on Women's Health. Excluding women who reported arthritis symptoms at the beginning of the study, the authors looked at those who began reporting stiff or painful joints 'often' and how much exercise they undertook.



The results suggest that for women in the older age bracket, doing a little over an hour of moderate physical activity each week will lessen your chances of developing frequent arthritis symptoms in the next three years. Pushing that up to 2 ?? hours per week is even more likely to prevent arthritis symptoms appearing. These results were not seen for the middle-aged group.



A debilitating health problem which is more likely to strike as we get older and affects more women than men, arthritis is almost as common as cardiovascular disease in Australia, affecting 17% of the population. By 2020 this figure is set to approach US levels, where arthritis is the most prevalent chronic condition for middle aged and older people, affecting over a fifth of the population. Exercising into old age could ensure movement without stiffness and pain for longer, and could reduce the burden of arthritis on the healthcare system.





Relationship between physical activity and stiff or painful joints in mid-aged and older women: a 3 year prospective study

Kristiann C Heesch, Yvette D Miller and Wendy J Brown

Arthritis Research & Therapy

Psoriatic Arthritis: New Drug Shows Promising Results

Psoriatic arthritis affects about 11 percent of patients with psoriasis. Anti-tumor necrosis factor ?± (anti-TNF?±) agents, which block signaling molecules that induce inflammation, improve the symptoms of psoriatic arthritis. Golimumab is a new human monoclonal antibody that works against TNF?± and has been shown to be beneficial within two weeks of the first subcutaneous injection in a phase II rheumatoid arthritis trial. A new phase III, multicenter, randomized, double-blind, placebo-controlled trial, the largest of its kind to be completed with a biologic agent to treat psoriatic arthritis and the first placebo-controlled study evaluating the effect of a TNF inhibitor on nail psoriasis, found that golimumab significantly improved active psoriatic arthritis and associated skin and nail psoriasis. The study was published in the April issue of Arthritis & Rheumatism (www3.interscience.wiley/journal/76509746/home).



Led by Arthur Kavanaugh of the University of California San Diego in La Jolla, CA the study involved 405 patients with active psoriatic arthritis even after having taken disease-modifying antirheumatic drugs or nonsteroidal anti-inflammatory drugs. Patients were randomized to receive subcutaneous injections of placebo, golimumab 50 mg, or golimumab 100 mg every four weeks for 24 weeks. Patients with less than 10 percent improvement in swollen and tender joints at week 16 were switched from placebo to 50 mg golimumab or from 50 mg to 100 mg. The primary end point of the study was the proportion of patients who met the American College of Rheumatology 20 percent improvement criteria (ACR20 response) at week 14. This response included at least a 20 percent improvement in swollen and tender joint counts and other measures such as pain, disease activity, physical function, and C-reactive protein. ACR50 and ACR70 responses were defined by at least 50 percent and at least 70 percent improvement.



The results showed that golimumab was efficacious and generally well tolerated. An ACR20 response was achieved at week 14 by 51 percent of patients receiving 50mg and 45 percent of those receiving 100mg, compared with 9 percent of placebo-treated patients. In addition, significantly more golimumab-treated patients than placebo-treated patients achieved ACR50 and ACR70 responses and those who initially showed little improvement and switched from placebo to golimumab or increased their dosage also showed improvement. Patients treated with the drug had significant improvement in physical function and health-related quality of life, as well as significant improvement in enthesitis, an inflammation where muscles attach to bones. In addition to improving arthritic symptoms, golimumab also improved psoriasis symptoms: 40 percent of the 50 mg group and 58 percent of the 100 mg group had at least 75 percent improvement in psoriasis symptoms, compared with 3 percent of the placebo group. "The safety profile of golimumab in psoriatic arthritis was similar to other anti-TNF agents that have been studied in this disease. Subcutaneous administrations were well tolerated. Only a small number of patients had injection site reactions, which were mostly mild.



This was also the first placebo-controlled study evaluating the effect of an anti-TNF?± on nail psoriasis, which affected about 70 percent of the patients involved in the study. Significant improvements in nail symptoms were seen in those treated with golimumab as early as week 14 and were maintained or improved through the end of the study period.



The authors conclude that "subcutaneous golimumab (at doses of 50 mg and 100 mg) administered every 4 weeks significantly improved active psoriatic arthritis and associated skin disease." Longer-term data on golimumab's efficacy and safety will be reported in the future.


Notes:


Article: Golimumab, a New Human Tumor Necrosis Factor ?± Antibody, Administered Every Four Weeks as a Subcutaneous Injection in Psoriatic Arthritis," Arthur Kavanaugh, Iain McInnes, Philip Mease, Gerald G. Krueger, Dafna Gladman, Juan Gomez-Reino, Kim Papp, Julie Zrubek, Surekha Mudivarthy, Michael Mack, Sudha Visvanathan, Anna Beutler, Arthritis & Rheumatism, April 2009.



Source:
Sean Wagner


Wiley-Blackwell

Rheumatologists Are Eager To Use Roche-Genentech's ACTEMRA, According To New Study By BioTrends

BioTrends is pleased to announce the publication of a new syndicated report, LaunchTrends®: ACTEMRA. Actemra (tocilizumab), marketed by Roche-Genentech, is the first IL-6 receptor inhibitor agent approved for rheumatoid arthritis. This report is the first in a three wave series and is derived from on-line survey responses from 77 rheumatologists and qualitative interviews with 20 rheumatologists.


At one month post launch, more than one-third of the survey respondents had already started to use Actemra in their patients and although the majority of respondents have the product slated as a third line (or later) option, many reported an expectation that Actemra could quickly advance to second line therapy following a single TNF failure. Even though most rheumatologists indicated that Actemra would likely replace Orencia or Rituxan in their practice, initial patient origination was largely from TNF failures. Overall, rheumatologists view the unique mechanism of action as Actemra's greatest attribute. Concerns with long term safety, certain side effects and managed care access could be potential obstacles to rapid adoption. In the next six months, more than 80% of the rheumatologists expect to be using Actemra in their practices.


LaunchTrends: Actemra is a three wave primary market research study that consists of a quantitative on-line survey and qualitative telephone interviews. In total, 300 rheumatologists will participate in the research. This report will capture launch effectiveness at one month, three months, and six months post launch. The reports are designed to assess trial and use of Actemra, obstacles to use, typical patient types, product perceptions, promotional efforts/messages, and satisfaction with the product relative to other agents. The next wave of the study will field in mid-April with the results available in early May 2010.


About BioTrends Research Group, Inc.


BioTrends Research Group, Inc. provides syndicated market research to pharmaceutical manufacturers competing in clinically evolving, specialty pharmaceutical markets.


About Decision Resources, Inc.


Decision Resources, Inc. is a cohesive portfolio of companies that offers best-in-class, high-value information and insights on important sectors of the healthcare industry. Clients rely on this analysis and data to make informed decisions.


All company, brand, or product names contained in this document may be trademarks or registered trademarks of their respective holders.


Source: BioTrends Research Group, Inc


View drug information on Actemra; Orencia; Rituxan.

ACTEMRA(TM) (tocilizumab) Third Phase III Study Results Show Significant Improvement In Symptoms Of Patients With Rheumatoid Arthritis

Roche today announced that
results from the ACTEMRA(TM) RADIATE (RheumAtoiD ArthritIs Study in
Anti-TNF FailurEs) trial successfully met its primary endpoint in patients
with moderate to severe rheumatoid arthritis (RA) who failed to respond to
anti-tumor necrosis factor treatments (anti-TNFs).



The trial - the third multinational Phase III study of ACTEMRA outside
of Japan - showed that a greater proportion of patients treated with
ACTEMRA plus methotrexate (4 mg/kg or 8 mg/kg) achieved a significant
reduction in the signs and symptoms of RA as evaluated by ACR20 following
24 weeks of treatment, compared to those who were treated with placebo plus
methotrexate.



ACTEMRA was generally well tolerated; the most common adverse events
reported more frequently in the ACTEMRA arms of the RADIATE trial were
nausea, headache, nasopharyngitis, diarrhea and upper respiratory tract
infection.



"The study results reconfirm the findings from the previous
multinational trials that interleukin-6 receptor inhibition is a novel
mechanism for reducing inflammation caused by RA," said Lars Birgerson,
M.D., Ph.D., Global Head Medical Affairs, Roche. "The data demonstrate that
ACTEMRA can potentially offer an effective approach in reducing the signs
and symptoms of RA, particularly when therapies such as anti-TNFs prove
insufficient."



Data from this trial will be submitted for presentation at upcoming
national scientific meetings. In addition, other Phase III trials exploring
ACTEMRA in RA are ongoing with another study scheduled to report in 2007.



About the RADIATE Study



The RADIATE (RheumAtoiD ArthritIs Study in Anti-TNF FailurEs) study is
a three-arm, randomized, double-blind, placebo-controlled study designed to
evaluate the safety and efficacy of ACTEMRA plus methotrexate (4 mg/kg or 8
mg/kg) compared to placebo plus methotrexate in RA patients who had an
inadequate response to anti-TNFs alone. Patients received either ACTEMRA
intravenously (4 mg/kg or 8 mg/kg) every four weeks plus methotrexate
weekly or placebo infusions every four weeks plus methotrexate weekly.



Data from the study were analyzed to determine patients' response to
treatment by using three standard assessments: ACR score (1), developed by
the American College of Rheumatology (ACR), DAS28 (2), a measurement of RA
disease activity, and EULAR response criteria (3), a measurement of
treatment response. The study included 498 patients at 128 trial sites in
13 countries, including the United States.
















The RADIATE trial is one of five Phase III clinical studies designed to
investigate ACTEMRA as a potential new treatment for RA. Roche and Chugai
have initiated the collaborative clinical development program that has
enrolled a total of more than 4,000 patients in 41 countries including the
United States and several European countries.



About ACTEMRA (tocilizumab)



ACTEMRA is the first humanized interleukin-6 (IL-6) receptor-inhibiting
monoclonal antibody and represents a novel mechanism of action to treat RA.
Studies suggest that reducing the activity of IL-6, one of several key
cytokines involved in the inflammatory process, may reduce inflammation of
the joints. The global ACTEMRA Phase III clinical development program is
designed to evaluate this clinical finding. The compound is not currently
approved in the United States.



The most common adverse events reported in ACTEMRA global clinical
studies are upper respiratory tract infections, headache, nasopharyngitis
and hypertension. As with other biological disease modifying anti-rheumatic
drugs (DMARDs), serious infections have been reported in some patients
treated with ACTEMRA.



About Rheumatoid Arthritis



Rheumatoid arthritis is a progressive, systemic autoimmune disease
characterized by inflammation of the membrane lining in the joints. This
inflammation causes a loss of joint shape and function, resulting in pain,
stiffness and swelling, ultimately leading to irreversible joint
destruction and disability. Characteristics of RA include redness,
swelling, pain, and movement limitation around joints of the hands, feet,
elbows, knees and neck that leads to loss of function. In addition, the
systemic symptoms of RA include fatigue, decreased hemoglobin and
osteoporosis and may contribute to shortening life expectancy by affecting
major organ systems. After 10 years, less than 50% of patients can continue
to work or function normally on a daily basis. RA affects more than 21
million people worldwide with approximately 2.1 million people affected in
the United States.



About Roche



Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S.
pharmaceuticals headquarters of the Roche Group, one of the world's leading
research-oriented healthcare groups with core businesses in pharmaceuticals
and diagnostics. For more than 100 years in the U.S., Roche has been
committed to developing innovative products and services that address
prevention, diagnosis and treatment of diseases, thus enhancing people's
health and quality of life. An employer of choice, in 2006, Roche was named
one of the Top 20 Employers (Science magazine), ranked the No. 1 Company to
Sell For (Selling Power), and one of AARP's Top Companies for Older
Workers, and in 2005, Roche was named one of Fortune magazine's Best
Companies to Work For in America. For additional information about the U.S.
pharmaceuticals business, visit our websites: rocheusa or
roche.us.


References


(1) ACR20, ACR50 and ACR70 represent the percentage of reduction (20%, 50%
or 70%) in certain RA symptoms and measures the number of tender
and swollen joints, pain, patient's and physician's global assessments
and certain laboratory markers. An ACR70 response is considered
exceptional and represents a significant improvement in a patient's
condition.


(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 less than or equal to
3.2), moderate (3.2 < DAS28 less than or equal to 5.1) or high (DAS28
>5.1). DAS28

Cost Effectiveness Study Supports Use Of EUFLEXXA(TM) By Rheumatologists For Pain Relief In Patients With Knee Osteoarthritis

Ferring Pharmaceuticals presented the
results of a cost-utility study supporting the adoption of EUFLEXXA(TM) (1%
sodium hyaluronate) intra-articular hyaluronic acid (HA) for the relief of
pain in patients with osteoarthritis (OA) of the knee at the American
College of Rheumatology's Annual Scientific Meeting in Boston, MA, November
6-11.



Using data from a larger trial, the study demonstrated that an intra-
articular treatment course of HA (EUFLEXXA(TM)) for knee OA, as compared
with non-HA therapy, provides a cost-utility benefit that supports adopting
this technology. The data also show that wider adoption of this technology
would result in greater financial savings to the health care system.
Osteoarthritis is one of the most common diseases seen in the
rheumatologist's office, costing the health care system nearly $100 billion
per year. (1)



"While the use of intra-articular HA is increasing, little has been
published about its cost-effectiveness," said Erol Onel, MD, Director of
Medical Affairs at Ferring. "This study is important because it not only
presents rheumatologists with significant analysis regarding the
cost-benefit of using this treatment, but it also demonstrates a
potentially significant savings to our overall health care system." More
information regarding the cost-effectiveness of various OA treatment
therapies is available in the Ferring-sponsored OA Trends in Managed Care
Report.



About the Study



The study of 160 patients with knee OA compared costs and the extension
of quality-adjusted life years (QALY) in patients using hyaluronic acid
(HA) with those using a non-HA treatment for this condition. Patients were
randomized either to receive three 2 ml injections of EUFLEXXA(TM) or to be
in a control group maintained on their prior non-HA therapy. Patients'
utility scores were estimated and used to calculate QALYs. To determine
costs, in addition to the costs of HA, patients who responded to HA
treatment were assigned costs of health care utilization attributed to
patients without OA, and non-responders were assigned costs of health care
resources consumed by OA patients. Cost- effectiveness was expressed as
average and incremental cost per QALY.



The responder rate for patients in the HA treatment arm was
approximately 83 percent, and the mean QALY gained was 0.0877 for each
patient responding to treatment with HA over baseline values. When the
change of QALY of the non- responders was set as zero, the HA treatment
yielded a cost-utility ratio of $38,964, while that of the control group
ranged from $36,077 (assuming a 75 percent response rate) to $139,648 (25
percent response rate).



The study concluded that the cost-utility ratio for EUFLEXXA(TM) is
within the range needed to adopt a new technology, and that the product's
wider adoption would result in greater savings to the health care system.



About EUFLEXXA(TM)
















EUFLEXXA(TM) (1% sodium hyaluronate) is the first and only non-avian
derived hyaluronic acid approved in the U.S. for the treatment of pain
caused by knee osteoarthritis and is indicated for a three-injection
treatment regimen for patients who have failed to respond adequately to
conservative non-pharmacologic therapy and simple analgesics (eg,
acetaminophen). In a prospective, randomized, double-blind, head-to-head
study versus the market leading HA therapy, significantly more patients
were "pain free" and "symptom free" with EUFLEXXA(TM).(2)



The process used to manufacture EUFLEXXA(TM) produces the HA that most
closely resembles the HA in healthy human synovial fluid and the most
highly purified HA product available today. In addition, since it is not
derived from an avian source (chicken or rooster combs), the risk of
reactions related to avian proteins is eliminated.(3-8)



EUFLEXXA(TM) received PMA approval from the U.S. Food and Drug
Administration (FDA) on December 3, 2004, and became available to the
public on November 8, 2005. For more information, visit EUFLEXXA.



About Ferring Pharmaceuticals Inc.



Ferring Pharmaceuticals Inc., part of the Ferring Group, is a privately
owned, international pharmaceutical company. Ferring's line of orthopaedic
products includes EUFLEXXA(TM), hyaluronic acid for pain from
osteoarthritis in the knee. Urology products include degarelix for prostate
cancer (Phase III) and Minirin Melt for bladder dysfunction (Phase III) ferringusa.



Ferring also markets BRAVELLE(R) (urofollitropin for injection,
purified), MENOPUR(R) and REPRONEX(R) (menotropins for injection, USP),
Novarel(R) (chorionic gonadotropin for injection, USP) and ENDOMETRIN
(progesterone) Vaginal Insert, 100 mg in the U.S. to infertility
specialists and their patients. Ferring also offers the Q.CAP(TM), the
first and only needle-free reconstitution device, for use with its
fertility treatments.



Other products include ACTHREL(R) (corticorelin ovine triflutate for
injection) for the differential diagnosis of Cushing's syndrome and
DESMOPRESSIN ACETATE in injectable and rhinal tube forms for the treatment
of diabetes insipidus and primary nocturnal enuresis.



The Ferring Group specializes in the research, development and
commercialization of compounds in general and pediatric endocrinology,
urology, gastroenterology, obstetrics/gynecology and infertility.


References


1. Centers for Disease Control and Prevention. MMWR. 2004;53:388-389



2. Kirchner M, Marshall D. A double-blind randomized controlled trial
comparing alternate forms of high molecular weight hyaluronan for the
treatment of osteoarthritis of the knee. Osteoarthritis Cartilage.
2006; 14:154-162.



3. Schiavinato A, Finesso M, Cortivo R, & Abatangelo G (2002). Comparison
of the effects of intra-articular injections of Hyaluronan and its
chemically cross-linked derivative (Hylan G-F20) in normal rabbit knee
joints. Clin Exp Rheumatol 20, 445-454.



4. Goomer RS, Leslie K, Maris T, & Amiel D (2005). Native hyaluronan
produces less hypersensitivity than cross-linked hyaluronan. Clin Orthop
Relat Res 239-245.



5. Leopold SS, Warme WJ, Pettis PD, & Shott S (2002). Increased frequency
of acute local reaction to intra-articular hylan GF-20 (synvisc) in
patients receiving more than one course of treatment. J Bone Joint Surg
Am 84-A, 1619-1623.



6. Puttick MP, Wade JP, Chalmers A, Connell DG, & Rangno KK (1995). Acute
local reactions after intraarticular hylan for osteoarthritis of the
knee. J Rheumatol 22, 1311-1314.



7. Pullman-Mooar S, Mooar P, Sieck M, Clayburne G, & Schumacher HR (2002).
Are there distinctive inflammatory flares after hylan g-f 20
intraarticular injections? J Rheumatol 29, 2611-2614.



8. Chen AL, Desai P, Adler EM, & Di Cesare PE (2002). Granulomatous
inflammation after Hylan G-F 20 viscosupplementation of the knee : a
report of six cases. J Bone Joint Surg Am 84-A, 1142-1147.


Ferring Pharmaceuticals

FerringUSA


View drug information on Degarelix; Desmopressin Acetate; Synvisc, Synvisc-One.

New Insight May Help Avoid Unnecessary Hand Surgery In Elderly

Motor nerve conduction is a common clinical test used to diagnose nerve problems such as carpal tunnel syndrome. Current techniques use a single recording site over a superficial muscle. This approach does not take into account the electrical contributions from the other muscles innervated by the nerve being stimulated. This study recorded 15 sites over the thenar eminence (muscles at the base of the thumb) during motor nerve conduction studies. Data suggest that standard nerve conduction studies in elderly patients with a common arthritic change in the thumb may result in unnecessary hand surgery.







Highlight from JRRD pg. 821



Contact: Dr. Stacieann Yuhasz

yuhaszvard

VA Research Communications Service

Arana Files IND For Lead Anti-Inflammatory Product ART621 In Rheumatoid Arthritis (RA) Indication

Biotechnology company Arana Therapeutics Limited (ASX: AAH) announced it has submitted an Investigational New Drug application (IND) to the FDA (U.S. Food and Drug Administration) for the anti-inflammatory product ART621 in a rheumatoid arthritis (RA) indication.


The IND includes a Phase II dose ranging study of ART621/221 in RA which is planned to be an international multi-centred trial of approximately 200 patients.


The study is designed to establish the appropriate dosing for ART621 in RA and will compare three doses of ART621 with a placebo in patients also taking methotrexate. Arana expects to commence recruitment for the study in late quarter 4 2008, subject to FDA feedback.


Taking into account their global expertise and experience, the management of the study has been awarded to Quintiles Transnational, the world's largest contract research organisation.


Commenting on these developments, CEO John Chiplin said: "We are very excited that ART621 has reached this important milestone - being Arana's first IND. We are now a confirmed clinical stage company and with our strong pipeline look forward to filing more IND's in the future."



About Arana Therapeutics


Arana Therapeutics (ASX: AAH) is an international biopharmaceutical company focussed on developing next generation antibody based drugs that will improve the lives of patients with inflammatory diseases and cancer.


Arana Therapeutics' innovative engineering technologies provide the basis for developing its next generation antibody candidates. Arana Therapeutics has the financial strength and management expertise to develop its product pipeline.


Arana has a significant track record of commercialising its technologies and has partnerships with GSK, CSL, Centocor (J&J) and Abbott Laboratories.


Additional information


ART621 is an "anti-TNF" - a class of drugs used for the treatment of inflammatory diseases such as rheumatoid arthritis, psoriasis and Crohn's disease. ART621 works by blocking the action of TNF (tumour necrosis factor) a protein which is involved in the generation of inflammation



Arana Therapeutics

Japan Approves ENBREL to Treat Rheumatoid Arthritis

Wyeth Japan and Takeda Pharmaceutical Company, Limited (Takeda Pharmaceutical) today announced that ENBREL(R)
(etanercept) has been approved by the Japan Ministry of Health, Labour and Welfare (MHLW) for the treatment of rheumatoid
arthritis (RA) in patients who had an inadequate response to existing therapies. As announced earlier, Enbrel in Japan will
be co-promoted by both Wyeth and Takeda Pharmaceutical.


"We are pleased with the approval decision and following pricing approval, we will make the product available to Japanese
patients as soon as possible," says Rune Bremberg, President, Wyeth Japan.


ENBREL is the only fully human, anti-TNF receptor approved to reduce the signs and symptoms of RA in patients who had an
inadequate response to traditional disease-modifying antirheumatic medicines. The biological product can be used alone as a
monotherapy and is administered twice weekly as a subcutaneous injection. Initially the product will be made available to
medical institutions participating in an all-patient surveillance program.


ABOUT RHEUMATOID ARTHRITIS


Rheumatoid arthritis is a chronic and potentially disabling disorder that affects about 700,000 people in Japan. The serious
rheumatic disease causes the body's immune system to attack the lining of the joints, resulting in pain and swelling and may
lead to fatigue, disability, deformity, organ damage, or premature death if not managed effectively. In RA, the immune system
attacks the body's own healthy cells, mistaking them for cells that don't belong. This causes inflammation in the lining and
connective tissues of the joints.


Generally, in Japan the disease affects about four times as many women as men. RA can develop at all ages including
childhood; in most cases it develops between the ages of 25 and 50.


ABOUT ENBREL


Globally physicians have become familiar with the benefits and proven long-term profile of ENBREL. As of today, the product
has been approved in more than 70 countries around the world, and has been used to treat more than 280,000 patients worldwide
across various indications.


ENBREL acts by binding TNF, one of the dominant inflammatory cytokines or regulatory proteins that play an important role in
both normal immune function and the cascade of reactions causing the inflammatory process of rheumatoid arthritis. The
binding of ENBREL to TNF renders the bound TNF biologically inactive, resulting in significant reduction in inflammatory
activity.


Additionally, ENBREL binds to lymphotoxin (LT)-alpha, another cytokine involved in the inflammatory process of RA.















ABOUT WYETH


Wyeth (NYSE: WYE) is one of the world's largest research-driven pharmaceutical and health care products companies. It is a
leader in the discovery, development, manufacturing, and marketing of pharmaceuticals, vaccines, biotechnology products and
nonprescription medicines that improve the quality of life for people worldwide. The Company's major divisions include Wyeth
Pharmaceuticals, Wyeth Consumer Healthcare, and Fort Dodge Animal Health.


The statements in this press release that are not historical facts are forward-looking statements based on current
expectations of future events that involve risks and uncertainties including, without limitation, risks associated with the
inherent uncertainty of the timing and success of pharmaceutical research, product development, manufacturing,
commercialization, economic conditions including interest and currency exchange rate fluctuations, changes in generally
accepted accounting principles, the impact of competitive or generic products, trade buying patterns, wars or terrorist acts,
product liability and other types of lawsuits, the impact of legislation and regulatory compliance and obtaining
reimbursement, favorable drug pricing, access and other approvals, environmental liabilities, and patent, and other risks and
uncertainties, including those detailed from time to time in the Company's periodic reports, including current reports on
Form 8-K, quarterly reports on Form 10-Q and the annual report on Form 10-K, filed with the Securities and Exchange
Commission.


Actual results may vary materially from the forward-looking statements. The Company assumes no obligation to publicly update
any forward-looking statements, whether as a result of new information, future events or otherwise.


wyeth


View drug information on Enbrel.

Rheumatoid Arthritis Patients Benefit From Vegan, Gluten-free Diet

A gluten-free vegan diet may improve the health of patients with rheumatoid arthritis, according to new research from Karolinska Institutet. The diet has a beneficial effect on several risk factors for cardiovascular disease.



Rheumatoid arthritis is associated with an increased risk of atherosclerosis (hardening of the arteries) and cardiovascular diseases. The underlying causes are unknown, but researchers suspect that the disturbed balance of blood fats seen in patients with rheumatoid arthritis may be part of the explanation.



A research team at Karolinska Institutet has shown in a new study that a gluten-free vegan diet has a beneficial effect on cardiovascular risk factors in people with rheumatoid arthritis. The effect was seen when a group of patients who kept to a gluten-free vegan diet for a year were compared with a control group which had followed ordinary dietary advice.



Vegan food had a positive effect on symptoms of the disease, which were more pronounced in the control group. Blood levels of oxidised LDL-cholesterol, a risk factor for atherosclerosis, were also lower in the group which kept to the vegan diet. The vegan group also had higher levels of anti-PC, a type of antibody that the researchers believe has a protective effect against atherosclerosis.



"Our findings suggest a new mechanism by which the level of natural protective antibodies can be increased. They also show that diet can have effects on the immune system with implications for the incidence of disease", says Professor Johan Frosteg??rd, who led the study.



The study was initiated by Professor Ingi?¤ld Hafstr?¶m and was carried out within the framework of CVDIMMUNE, an EU consortium of ten European partners led by Johan Frosteg??rd. The consortium is studying the significance of anti-PC in the hope of developing a vaccine against atherosclerosis.


'Gluten-free vegan diet induces decreased LDL and oxidized LDL levels and raised atheroprotective natural antibodies against phosphorylcholine in patients with rheumatoid arthritis; A randomized study'

Ann-Charlotte Elkan, Beatrice Sj?¶berg, Bj?¶rn Kolsrud, Bo Ringertz, Ingi?¤ld Hafstr?¶m and Johan Frosteg??rd

Arthritis Research & Therapy, 18 March 2008.


Karolinska Institutet is one of the leading medical universities in Europe. Through research, education and information, Karolinska Institutet contributes to improving human health. Each year, the Nobel Assembly at Karolinska Institutet awards the Nobel Prize in Physiology or Medicine. For more information, visit ki.se

Results Of First Multinational Study Of Tocilizumab

Nearly half (43.9%) of rheumatoid arthritis (RA) patients receiving tocilizumab 8mg/kg, in addition to ongoing methotrexate therapy experienced a 50% (ACR50) improvement in symptoms at 24 weeks and more than one fifth achieved a 70% symptom improvement, according to results of a European study presented at EULAR 2007, the Annual European Congress of Rheumatology in Barcelona, Spain. This study is the first phase III trial of tocilizumab.



Lead researcher Dr Josef Smolen of the Medical University of Vienna for Internal Medicine commented, "These data show the potential of tocilizumab as a novel and attractive approach to treating RA. The symptom improvements observed across both 4mg/kg and 8mg/kg doses show that tocilizumab offers significant promise to patients with moderate and severe RA."



Significant improvement in symptoms was observed in all patients receiving tocilizumab and methotrexate compared to placebo and methotrexate. At 24 weeks, an ACR70 (70% symptom improvement) was observed in 22%, an ACR50 (50% symptom improvement) in 43.9% and an ACR20 (20% symptom improvement) in 58.5% of patients receiving 8mg/kg tocilizumab plus methotrexate compared to placebo (2.0% p=

Study Of Tough Hydrogel For Synthetic Cartilage Replacement

Some 46 million people suffer from arthritis in the United States alone. The worst cases require painful surgeries to drill holes in and reinforce joints. Now researchers working at the National Institute of Standards and Technology (NIST) are studying an unusually pliant yet strong synthetic cartilage replacement in hopes of providing arthritis victims with some relief. In a paper* presented at the March Meeting of the American Physical Society, NIST scientists and colleagues from Hokkaido University in Japan, reported on a gel that, while having the pliancy of gelatin, won't break apart even when deformed over 1,000 percent. By using NIST's neutron research facility to show how the molecules in the gel sustain such large deformations, the research team hopes to make it easier to design materials with even better mechanical properties.



Known as double-network hydrogels, the incredible strength of these new materials was a happy surprise when first discovered by researchers at Hokkaido in 2003. Most conventionally prepared hydrogels - materials that are 80 to 90 percent water held in a polymer network - easily break apart like a gelatin. The Japanese team serendipitously discovered that the addition of a second polymer to the gel made them so tough that they rivaled cartilage - tissue which can withstand the abuse of hundreds of pounds of pressure. A combination of a brittle hydrogel and a soft polymer solution leads to a surprisingly tough material.



Initial work using NIST's neutron scattering techniques to explore the structure of the gel found unexpected results. The two polymers** were attracted to each other - despite the fact that one polymer is negatively charged and the other neutral - and can withstand a certain force before they can be pulled apart. The total amount of force that can be endured by this polymer pair gets amplified enormously because there are many contacts along each long chain. Efficacy of stress transfer between the long added chain and gel network forms the cornerstone of the toughening mechanism in DN-gels.



The latest paper discusses a molecular-level toughening mechanism proposed based on neutron scattering measurements that gather, in detail, how the two polymers behave when the gel is deformed. Under deformation, these two polymers arrange themselves into an alternating, well-ordered, periodic pattern that is repeated approximately every 2 microns. This periodic structure is a hundred times larger than what is usually seen in molecules under deformation and its formation elegantly dissipates a large amount of deformation energy to stabilize the gel from crumbling apart.



Establishing the details of the molecular structure will allow for more precise design of the next generation of hydrogels that are tough and rigid at the same time. Real cartilage goes through a process of constant daily destruction and regeneration under everyday stresses; the researchers hope a good synthetic cartilage could endure year after year under the rigors of the body before needing to be replaced.







* W.L. Wu, V.R. Tirumala, T. Tominaga, S. Lee, P. Butler, E.K. Lin, J.P. Gong, H. Furukawa, A molecular model for toughening in double-network hydrogels. Presented at the March Meeting of the American Physical Society, March 11, 2008, New Orleans, La. Session: J25.00006.



** The materials is made by adding polyacrylamide (PAAm) to a gel based on poly(2-acrylamide,2-methyl,1-propanesulfonicacid) (PAMPS).



Source: Michael Baum


National Institute of Standards and Technology (NIST)

Anti-Tumor Necrosis Factor Treatment Does Not Increase Cancer Risk In RA Patients

A recent study by Swedish researchers found that rheumatoid arthritis (RA) patients did not experience an elevated cancer risk in the first 6 years after starting anti-tumor necrosis factor (TNF) therapy. The research team, led by Johan Askling, M.D., Ph.D., from Karolinska University Hospital in Stockholm, Sweden assessed the short-term and medium-term cancer risk for RA patients using anti-TNF therapies: infliximab, adalimumab, and etanercept. Details of the study appear in the November issue of Arthritis & Rheumatism, a journal of the American College of Rheumatology published by Wiley-Blackwell.



TNF is a cytokine (substance secreted by immune system cells) that regulates the body's immune system and is involved in inflammation. TNF inhibitors (or TNF blockers) are a class of therapies used to reduce inflammation in chronic inflammation such as RA. The common immunosuppressant drugs and those included in the study are Remicade®, HumiraTM, and Enbrel®. As these therapies are used to treat chronic inflammatory illnesses, the long-term inhibition of TNF raises concerns for increased risk of infections and cancer.



This study, one of the largest and longest population-based assessments of cancer risks associated with immunosuppressive therapy, included data from several Swedish databases including the Biologics Register, the Cancer Register, and the Early RA Register. Researchers identified and analyzed data from 6,366 patients who started anti-TNF therapy between January 1999 and July 2006. Data from patients using TNF inhibitors was compared with other groups of RA patients - 61,160 not taking medication, 4015 using methotrexate (the gold standard in RA treatment) and 4,015 taking combinations of disease -modifying anti-rheumatic drugs (other than TNF inhibitors).



Results show there were 240 first primary cancers diagnosed during the 25,693 person-years of follow-up in the patients using anti-TNF therapy who had no history of cancer at the onset of immunosuppressant treatment. When compared to the larger national RA cohort who did not receive TNF inhibitors or have a history of cancer, the relative risk of anti-TNF therapy was 1.00 and remained unchanged for those taking immunosuppressant drugs for up to 6 years. "Our research indicates the overall cancer risk is the same for RA patients on immunosuppressant therapies and those not taking medications for the disease," confirmed Dr. Askling, but adds that "given several remaining uncertainties, continued vigilance remains prudent."



Rheumatoid Arthritis (RA) is an autoimmune disease characterized by chronic inflammation in the joints, joint tissue, and other organs and is the most common form of inflammatory arthritis. A 2004 report from the World Health Organization (WHO) estimates 23.7 million people worldwide (1.3 million U.S. adults) are afflicted with RA, with 75% of those cases found in women.



Article: "Cancer Risk in Patients With Rheumatoid Arthritis Treated With Anti-Tumor Necrosis Factor a Therapies." Johan Askling, Ronald F. van Vollenhoven, Fredrik Granath, Pauline Raaschou, C. Michael Fored, Eva Baecklund, Christina Dackhammar, Nils Feltelius, Lars C?¶ster, Pierre Geborek, Lennart T. Jacobsson, Staffan Lindblad, Solbritt Rantap?¤?¤-Dahlqvist, Tore Saxne, and Lars Klareskog. Arthritis & Rheumatism; Published Online: October 29, 2009 (DOI 10.1002/art.24941); Print Issue Date: November 2009



Source: Dawn Peters


Wiley-Blackwell


View drug information on Enbrel; Remicade.

La Jolla Institute For Allergy & Immunology Researchers Identify A Potential Role For Retinoic Acid In Autoimmune And Inflammatory Diseases

An important finding, which could eventually lead to a new therapeutic approach for treating autoimmune and inflammatory diseases such as rheumatoid arthritis, colitis, psoriasis and others, was announced today by researchers at the La Jolla Institute for Allergy & Immunology (LIAI). The studies, conducted in laboratory mice, demonstrated the role of retinoic acid, a substance derived when Vitamin A is broken down in the body, in regulating inflammation.



In their studies, published yesterday in the online version of the journal Science, the LIAI researchers showed that by manipulating the amount of retinoic acid in mice, they could affect the number of pro-inflammatory T cells, a type of white blood cell responsible for several autoimmune and inflammatory diseases. The finding is an important first step that, if eventually found to be true in humans, points to the potential of a new avenue of therapies using retinoic acid to treat these diseases.



"What's exciting about this finding is they've found that retinoic acid plays a role in modulating the switch between these two distinct (T cell) lineages - the induced regulatory T cells, which are anti-inflammatory, and the TH-17 lineage, which promotes inflammatory responses, " said Casey Weaver, M.D., a University of Alabama, Birmingham, professor and prominent immunology researcher, who was key in the discovery of TH-17 in 2005.



Further, Dr. Weaver said, the LIAI researchers had developed a "mechanism by which you can prevent the development of the (inflammatory) lineage. This is very exciting because it provides a potential pharmacological application for this finding."



The finding was published today in a paper entitled "Reciprocal Th-17 and regulatory T cell differentiation mediated by retinoic acid." Hilde Cheroutre, Ph.D., led the research team, entirely from LIAI, in which Daniel Mucida, Ph.D., and Yunji Park, Ph.D., were key contributors.



The LIAI team tested three approaches with retinoic acid. In one model, they injected the mice with retinoic acid, essentially giving them more of the substance than they would have through normal body processes. This suppressed the formation of pro-inflammatory T cells in the intestines of the mice, demonstrating that increases in retinoic acid reduced inflammation. In another approach, designed to test how reducing retinoic acid would affect inflammation, the team used an inhibitor to block retinoic acid in the mice. This led to the decrease of anti-inflammatory T cells, showing that reducing retinoic acid increased inflammation. In a third, particularly exciting approach, the scientists treated T cells with retinoic acid in a test tube. When put back into the mice, these T cells prevented the formation of inflammatory T cells in the mice. This is especially noteworthy because combining the retinoic acid and T cells outside the body may avoid possible side effects that are more likely when scientists attempt to manipulate body processes internally.



"We found that you can control inflammation in a living animal with retinoic acid or you can treat cells with retinoic acid in a test tube and transfer them to the organism to suppress inflammation in vivo," said Dr. Cheroutre. "This may offer an important new avenue for treatment of autoimmune diseases like colitis and rheumatoid arthritis or other inflammatory diseases, as well as potentially providing a mechanism for the control of graft rejections, where you don't want the immune system to attack the grafted tissue."



About LIAI


Founded in 1988, the La Jolla Institute for Allergy and Immunology is a nonprofit medical research center dedicated to increasing knowledge and improving human health through studies of the immune system. Scientists at the institute carry out research searching for cures for cancer, allergy and asthma, infectious diseases, and autoimmune diseases such as diabetes, inflammatory bowel disease and arthritis. LIAI's research staff includes more than 100 Ph.Ds.



liai

Breastfeeding Reduces Risk Of Rheumatoid Arthritis

Women who breast feed for a longer period of time are less likely to
get rheumatoid arthritis, according to a study published on May 13,
2008 in the Annals of the Rheumatic Diseases, a BMJ Specialist journal.




In the last thirty years, the fraction of women breastfeeding for more
than six months has increased substantially. This study examined the
effects of breast feeding, administration of oral contraceptives, and
having children (but not breast feeding) on rheumatoid arthritis. The
investigators studied 136 women with rheumatoid arthritis and 544 women
without the disease.



The only group that experienced reduced rheumatoid arthritis had
children and breastfed for extended periods of time. Those who
breastfed longer were more likely to decrease arthritis risk. In
comparison to the group that never participated in breastfeeding, women
who had breastfed
for one to 12 months had only three-quarters the chance of getting the
disease. Women who had breastfed for 13 months or more had half the
chance of getting rheumatoid arthritis as those who had never
breastfed.



Notably, this relationship was not found with the use of oral
contraceptives, which mimic the hormonal effects of pregnancy.



The authors concluded that there was some difficulty in drawing a
direct connection between the higher rates of breast feeding and the
correlating drop in the number of women affected by rheumatoid
arthritis. However, they claim that the study shows another reason why
women might consider to continue breast feeding.



Breast feeding, but not use of oral contraceptives, is
associated with a reduced risk of rheumatoid arthritis

M Pikwer, U Bergstrom, J-A Nilsson, L Jacobsson, G Berglund, C Turesson

Online First Annals of the Rheumatic Diseases 2008;


doi:10.1136/ard.2007.084707

Click
Here For Abstract



Written by Anna Sophia McKenney

Combining Medications Often Best Strategy To Battle Rheumatoid Arthritis

For patients with rheumatoid arthritis, combining one well-known, lower cost synthetic drug with one of six biologic medications often works best to reduce joint swelling or tenderness, according to a new report funded by the Agency for Healthcare Research and Quality, part of the U.S. Department of Health and Human Services. An article based on the report will be posted on-line Monday in the Annals of Internal Medicine.


Researchers reviewed published evidence to compare the benefits and harms of three classes of medications: synthetic disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, and corticosteroids. Synthetic DMARDs include hydroxychloroquine, leflunomide, methotrexate and sulfasalazine; biologic DMARDs include abatacept, adalimumab, anakinra, etanercept, infliximab and rituximab; and corticosteroids include drugs such as prednisone.


The report concluded that combining methotrexate, a synthetic DMARD, with one of the biologic DMARDs works better than using methotrexate or a biologic DMARD alone. The report also found that methotrexate works as effectively as the biologic DMARDs adalimumab and etanercept for patients who have early rheumatoid arthritis. Adalimumab and etanercept, however, show better short-term results as measured by X-rays of joints. The report also emphasized that biologic DMARDs and methotrexate increase the risk of serious infection, including a reoccurrence of tuberculosis.


"Rheumatoid arthritis is a painful, degenerative disease that affects people of all ages and can profoundly impact quality of life," said AHRQ Director Carolyn M. Clancy, M.D. "This report establishes a clear, unbiased summary of what is known about current treatments. It also identifies areas where more research is needed."


About 2 million Americans have rheumatoid arthritis, a long-term illness that causes joint and tissue inflammation. Rheumatoid arthritis is an autoimmune disease, meaning that the body confuses healthy tissue for foreign substances and attacks itself. The cause is unknown. The disease often begins with fatigue, morning stiffness, weakness and muscle aches. Eventually, joint pain appears. Pain may affect the wrists, knees, elbows, fingers, toes, ankles or neck. Other symptoms may include anemia, eye burning, limited range of motion, skin redness and swollen glands. Joint destruction may occur within 1 to 2 years after the disease appears. Some cases cause deformities. Treatment typically begins with medications but may include physical therapy and surgery.















Among other findings in the report:


- Combining prednisone with the synthetic DMARD hydroxychloroquine, methotrexate or sulfasalazine works better than using only a synthetic DMARD to reduce joint swelling and tenderness and to improve function.


- No meaningful clinical differences can be found between methotrexate and either leflunomide or sulfasalazine.


- Combining the synthetic DMARDs methotrexate and sulfasalazine is no more effective than using just one of the medications for patients with early rheumatoid arthritis.


- Not enough evidence exists to determine whether combining two biologic DMARDs is more effective than using one biologic DMARD.


- About 17 of every 1,000 people taking a biologic DMARD for 3 to 12 months have a serious infection. Combining two biologic DMARDs can increase the risk.


- Among biologic DMARDs, rates of painful injection site reactions are more common for anakinra (67 percent) than for etanercept (22 percent) or adalimumab (18 percent).


- More long-term research is needed on rheumatoid arthritis medications, including how the outcomes of these drugs vary among patients with different health conditions and demographic characteristics. More comparative studies on various combinations of drugs are critical. Also important is investigating whether taking the medications earlier (especially biologic DMARDs) is better for long-term outcomes.


The report, Comparative Effectiveness of Drug Therapy for Rheumatoid Arthritis and Psoriatic Arthritis in Adults, was authored by the AHRQ-funded RTI International-University of North Carolina Evidence-based Practice Center in Chapel Hill, NC. It is the newest analysis from AHRQ's Effective Health Care Program. That program represents an important federal effort to compare alternative treatments for significant health conditions and make the findings public. The program is intended to help patients, doctors, nurses and others choose the most effective treatments. Information on the program, including full reports and plain-language summary guides, can be found at effectivehealthcare.ahrq.

ahrq

FDA Accepts Application Approval Request of REMICADE(reg) for Psoriatic Arthritis

Supporting Data Show Significant Reduction of Joint and Skin Symptoms in Psoriatic Arthritis -


Centocor, Inc, announced today that the U.S. Food and Drug Administration (FDA) has accepted its filing of a supplemental
Biologics Licensee Application (sBLA) for REMICADE(reg) (infliximab) for the treatment of psoriatic arthritis (PsA) in patients
with active disease. PsA is a chronic, potentially debilitating disease, which affects approximately one million people and
causes joint inflammation frequently associated with active psoriasis.


"We are pleased that the FDA has accepted this application for REMICADE(reg) in the treatment of psoriatic arthritis," said
Cynthia Guzzo, senior director, Clinical Research, Centocor, Inc. "The results we have seen are extremely encouraging and we
hope to gain approval for patients impacted by this disease."


The filing is based on the results of two double-blind, placebo-controlled trials, IMPACT and IMPACT 2. The study results
were presented in October 2004 at the American College of Rheumatology Annual Scientific Meeting and in June 2004 at the
European League Against Rheumatism's Annual European Congress of Rheumatology.


IMPACT 2 is a Phase III, multi-center, randomized, double-blind, placebo-controlled trial that demonstrated that treatment
with REMICADE(reg) 5 mg/kg resulted in marked improvements in patients with PsA and significant improvement in both joint and
skin disease was evident as early as week two. These data showed that at week 14, more than half of the patients in the
REMICADE(reg) treatment group achieved significant improvements in the signs and symptoms of PsA as measured by the proportion of
patients achieving ACR 20 (58 percent of the REMICADE(reg) patient group versus 11 percent placebo, p less than 0.001) and 75
percent improvement in PASI (63.9 percent of the REMICADE(reg) treatment group versus 2.3 percent placebo, p less than 0.001).
The ACR 20 and PASI 75 responses were achieved regardless of concomitant methotrexate use or level of joint involvement at
baseline.


Furthermore, compared to placebo, significantly more subjects in the REMICADE(reg) treatment group achieved ACR 70 or PASI 90 as
early as week six and improved or maintained these results at later points in the study. At week 24, results showed that 27
percent of patients treated with REMICADE(reg) exhibited a 70 percent improvement in symptoms of arthritis (as measured by ACR
70) compared with two percent in the placebo group (p less than 0.001).


Thirty-nine percent of patients showed a 90 percent improvement in psoriasis (as measured by PASI 90) compared with zero
percent in the placebo group (p less than 0.001). In the first study, IMPACT, 104 people were randomized to REMICADE(reg) (5
mg/kg) or placebo. At week 16, 65 percent (n=34) of people on REMICADE(reg) therapy achieved ACR 20. Additionally, of the 38
people with evaluable psoriasis, 68 percent (n=15) achieved a 75 percent or greater improvement from baseline (PASI 75)
indicating clinically meaningful improvement in psoriasis. Significant improvements were maintained through one year.
















REMICADE(reg) was generally well tolerated in these studies, with similar numbers of patients experiencing adverse events (AE) in
each group. No deaths, cases of tuberculosis or other opportunistic infections were reported and serious infections and
infusion reactions were uncommon. Also, with the exception of one case of basal cell carcinoma in the placebo group, no
malignancies were reported. In general, the AE observed in these studies were consistent with those reported in other
indications, and most common AE included events that commonly occur in the general population. Significant laboratory
abnormalities were unusual, with an elevation in liver function tests during the IMPACT 2 trial being the most common
abnormality. Overall, there were slightly more patients with serious AE in the REMICADE(reg) group than in placebo. See Important
Information below.


About Psoriatic Arthritis


PsA involves joint pain and swelling that can lead to debilitation coupled with inflamed, scaly, red patches of psoriasis.
Symptoms may include stiffness and tenderness of the joints and surrounding tissue, reduced range of motion, nail changes and
redness and pain of the eye. Joints of the hands, wrists, knees, ankles, feet, lower back and neck are commonly affected.
Approximately one million Americans have PsA, and the disease affects both men and women equally, most commonly between the
ages 30 and 50.


About REMICADE(reg)


REMICADE(reg) is the global market leader among anti-tumor necrosis factor alpha (TNF-alpha) therapies and the only agent
approved for the treatment of both rheumatoid arthritis (RA) and Crohn's disease (CD) in North America, the European Union
and Japan, and was the first biologic approved for ankylosing spondylitis in the European Union. In the EU, REMICADE(reg) is
indicated for the treatment of ankylosing spondylitis in patients who have severe axial symptoms, elevated serological
markers of inflammatory activity and who have responded inadequately to conventional therapy.


In September, the European Commission gave approval for expanded labeling for REMICADE(reg), in combination with methotrexate,
for the treatment of active and progressive psoriatic arthritis in patients who have responded inadequately to disease
modifying anti-rheumatic drugs.


REMICADE(reg) is the only biologic indicated for the treatment of patients with moderately-to-severely active Crohn's disease who
have had an inadequate response to conventional therapy. REMICADE(reg) is also indicated for reducing the number of draining
enterocutaneous and rectovaginal fistulas and maintaining fistula closure in patients with fistulizing Crohn's disease.



REMICADE(reg) is unique among available anti-TNF biologic therapies. Unlike self-administered therapies that require patients to
inject themselves frequently, REMICADE(reg) is the only anti-TNF biologic administered directly by caregivers in the clinic or
office setting. In RA and CD patients, REMICADE(reg) is a two-hour infusion administered every eight weeks, following a standard
induction regimen that requires treatment at weeks zero, two and six.


As a result, REMICADE(reg) patients may require as few as six treatments each year. The safety and efficacy of REMICADE(reg) have
been well established in clinical trials over the past 12 years and through commercial experience with more than a half
million patients treated worldwide.


Important Information


Many people with heart failure should not take REMICADE(reg); so prior to treatment discussion of any heart condition with a
doctor is necessary. A doctor should be informed right away of new or worsening symptoms of heart failure (such as shortness
of breath or swelling of your ankles or feet.)


There are reports of serious infections, including tuberculosis (TB) and sepsis. Some of these infections have been fatal.
Tell your doctor if you have had recent or past exposure to people with TB.


Evaluation for TB should be performed. If latent (inactive) TB exists, a doctor should begin TB treatment before starting
REMICADE(reg). REMICADE(reg) can lower one's ability to fight infections, so if prone to or if a history of infection(s) exists, or
one develops any signs of an infection such as fever, fatigue, cough or the flu while taking REMICADE(reg), tell a doctor right
away. Also tell a doctor if you have lived in a region where histoplasmosis or coccidioidomycosis is common. Blood disorders
have been reported, some fatal. Tell a doctor if you develop possible signs of blood disorders such as persistent fever,
bruising, bleeding or paleness while taking REMICADE(reg). Nervous system disorders have also been reported.


Tell a doctor if there is a history of a disease(s) that affects the nervous system, or if one experiences any numbness,
weakness, tingling or visual disturbances while taking REMICADE(reg). Reports of lymphoma (a type of cancer) in patients on
REMICADE(reg) and other TNF blockers are rare but occur more often than in the general population; tell a doctor if there exists
a history of cancer.


Serious infusion reactions have been reported with REMICADE(reg), including hives, difficulty breathing and low blood pressure.
Reactions have occurred during or after infusions. In clinical studies, some people experienced the following common side
effects: respiratory infections (that may include sinus infections and sore throat), coughing and stomach pain or mild
reactions to infusion such as rash or itchy skin.


About Centocor, Inc.


Centocor, Inc., is a leading biopharmaceutical company that creates, acquires and markets cost-effective therapies that yield
long-term benefits for patients and the health care community. The company is dedicated to the research and development of
treatments for a wide range of Immune-Mediated Inflammatory Disorders (IMID), such as arthritis and inflammatory skin
diseases and for cancer. Centocor's products, developed primarily through monoclonal antibody technology, help physicians
deliver innovative treatments to improve human health and restore patients' quality of life. Centocor, Inc., is a wholly
owned subsidiary of Johnson & Johnson, the worldwide manufacturer of health care products.


Centocor, Inc., has exclusive marketing rights to REMICADE(reg) in the United States. Schering-Plough Corporation has rights to
market REMICADE(reg) in all other countries throughout the world, except in Japan and parts of the Far East where Tanabe Seiyaku,
Ltd., markets the product.

Abbott's Humira(R) (Adalimumab) Recommended By NICE For The Treatment Of Rheumatoid Arthritis, UK

The National Institute for Health and Clinical Excellence (NICE) recommended Humira (adalimumab) as an option for the treatment of adults with rheumatoid arthritis (RA). It is the second positive opinion for adalimumab for rheumatological conditions in as many months, having been recommended by NICE for the treatment of psoriatic arthritis in August of this year.[1]


Adalimumab, licensed in the UK since 2003, is indicated for the treatment of active RA in adults when the response to previous disease-modifying anti-rheumatic drug (DMARD) therapy has been inadequate. Today's announcement by NICE underscores the clinical value of the use of adalimumab as an effective option for the management of adults who have both:


- Active rheumatoid arthritis as measured by disease activity score (DAS28) greater than 5.1 confirmed on at least two occasions, 1 month apart.


- Undergone trials of two DMARDs, including methotrexate (unless contraindicated). A trial of a DMARD is defined as being normally of 6 months, with 2 months at standard dose, unless significant toxicity has limited the dose or duration of treatment.


Primary Care Trusts have a statutory duty to fund NICE technology appraisals within three months of publication.


"The recommendation of adalimumab in NICE's guidance is an important milestone for clinicians and patients alike," noted Dr Bruce Kirkham, Consultant Rheumatologist, Guy's & St Thomas' NHS Foundation Trust, London. "The efficacy of treatments such as adalimumab has long been recognised, and NICE's recommendation acknowledges this efficacy, while confirming both the clinical and economic rationale for their use."


RA is a chronic and progressive disabling condition characterised by inflammation of the synovial tissue of the joints. It causes tenderness and stiffness of joints leading to progressive destruction, and other symptoms such as pain and fatigue. It affects approximately 400,000 people in England and Wales. Of these, approximately 15% have severe disease.[2]


"People living with rheumatoid arthritis will welcome today's recommendation from NICE," commented Ailsa Bosworth, Chief Executive of the National Rheumatoid Arthritis Society. "In order to effectively manage RA, it is crucial that those of us with the disease have access to the right treatment at the right time. NICE's decision means there are more options - and fewer barriers - to people with RA having access to treatments that work."


About RA


Up to 600,000 people in the UK suffer from RA.[3],[4],[5] Unlike osteoarthritis, the most common form of arthritis, RA is an inflammatory disease of the joints, which can result in eventual destruction of the joints' interior and the surrounding bone, leading to disability. The joints most commonly affected during the beginning of the disease are the smaller joints of the fingers, feet and wrists. The elbows, knees, ankles and hips can be affected, but less often. Although there is no cure for RA, people continue to seek treatments that not only alleviate the pain and inflammation but also slow disease progression, thereby inhibiting the joint damage that can hinder patients from performing daily activities.















About HUMIRA® (adalimumab)


Adalimumab, in combination with methotrexate (MTX), is indicated for:


- The treatment of moderate to severe active RA in adults (aged 18 and over) when the response to DMARDs including MTX has been inadequate.


- The treatment of severe, active and progressive RA in adults not previously treated with MTX.


Adalimumab is also indicated for the treatment of adults with:

- Severe active ankylosing spondylitis (AS) who have had an inadequate response to conventional therapy.

- Active and progressive psoriatic arthritis (PsA) when the response to previous DMARD therapy has been inadequate.

- Severe, active Crohn's disease (CD), in patients who have not responded despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant; or who are intolerant to or have medical contraindications for such therapies.


For the RA, AS and PsA indications, adalimumab is usually administered as 40mg every other week as a single dose via subcutaneous injection using a pre-filled pen. The recommended dosing in CD is 80mg adalimumab at week 0 followed by 40mg at week 2 and 40 mg every other week thereafter.


Adalimumab has been shown to reduce the rate of joint damage in RA as measured by X-ray and improve physical function, when given in combination with MTX. Adalimumab can be given as monotherapy in case of intolerance to MTX or when continued treatment with MTX is inappropriate.


Please refer to the Summary of Product Characteristics for full information on adalimumab including contraindications, special warnings and precautions and side effect information.[6]


About Abbott


Abbott 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 65,000 people and markets its products in more than 130 countries.


References:


[1]. National Institute for Clinical Excellence. Adalimumab for the treatment of moderate-to-severe psoriatic arthritis - Guidance. August 2007 nice.uk .


[2]. National Institute for Clinical Excellence. Adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis. Guidance October 2007. nice.uk .


[3].Funding anti-TNF Therapies for Severe Resistant Rheumatoid Arthritis. Birmingham University 2004


[4]. Simpson C et al. The Patient's journey: rheumatoid arthritis. BMJ 2005; 331;887-889


[5]. Government Actuary's Department.
UK Base Population Estimates for mid-2003 accessed April 2007


[6]. Electronics Medicines Compendium Humira (adalimumab) Summary of Product characteristics emc.medicines.uk/



View drug information on Humira.

Array BioPharma Announces Top-Line Results In Two Phase 1 Clinical Trials

Array BioPharma Inc. (NASDAQ: ARRY) announced top-line results from its Phase 1 seven-day dose escalation trial up to 1,200 mg daily of p38 inhibitor, ARRY-797, in healthy volunteers. In addition, the top-line results were announced in a second study, where ARRY-797 was evaluated in a 28-day Phase 1b trial in stable rheumatoid arthritis (RA) patients taking methotrexate. This study compared two doses of ARRY-797 to placebo.


A preliminary analysis of both trials indicates that ARRY-797 was well tolerated with a pharmacokinetic profile consistent with earlier studies. In the 28-day, three-arm RA study with a total of 28 patients, ARRY-797 showed inhibition of CRP levels (marker of inflammation) only during the first three weeks of dosing and a beneficial reduction in NTx levels (marker of bone remodeling) throughout the study. In addition, ARRY-797 showed a trend to improve the patients' assessment of pain (VAS score) over the course of the study.


"In the 28-day RA study, ARRY-797 demonstrated a transient inhibition of the inflammatory biomarker CRP and a trend towards analgesic efficacy in the pain endpoint," said Kevin Koch, Ph.D., President and Chief Scientific Officer. "Since these results are similar to other p38 inhibitors evaluated in rheumatoid arthritis, these findings have led us to discontinue testing of ARRY-797 in chronic inflammatory diseases. We continue to believe that a p38 inhibitor holds promise in treating patients with cancer and sub-chronic pain."


The Company continues to conduct a full analysis of safety, pharmacokinetics and efficacy data from both studies. Array anticipates that complete results from the studies will be presented at a medical conference in 2010. Based on these preliminary results, Array plans to cease the enrollment of new patients in its current clinical trial of ARRY-797 in ankylosing spondylitis patients.


Phase 1b Dose Escalation Trial in Healthy Volunteers: Clinical Study Design and Results


This Phase 1b dose escalation trial was a randomized, double-blind, placebo-controlled study in healthy volunteers and was designed to evaluate the safety and pharmacokinetics of ARRY-797 after single-day and multiple-day administration of ARRY-797. Single ascending-doses of 900 mg (once) and 1,200 mg/day (800 mg followed by 400 mg 12 hours later), and multiple-day, ascending-doses of 200, 300 and 400 mg/day TID (every eight hours) for eight consecutive days were explored.


Safety, Tolerability and Pharmacokinetics: Overall, ARRY-797 was well-tolerated after single-day and multiple-day administration of total daily doses of 600 mg, 900 mg, and 1,200 mg. In the multiple-day cohorts up to 400 mg TID, no adverse event (AE) was reported by more than one subject in any treatment group and all AEs were considered mild in intensity. In the single-day cohorts, mild dizziness was reported by two of the 6 subjects receiving a 900 mg dose of ARRY-797 and moderate dizziness by one of the 6 subjects receiving 800 mg followed by 400 mg ARRY-797. Approximately dose-proportional increases in mean total and peak exposures were observed with increasing dose following single- and multiple-dose administration. Mean plasma concentrations of ARRY-797 reached steady-state on day two after repeat-dose administration with modest accumulation.















Phase 1b 28-day Study in Patients with RA: Clinical Study Design and Results


This Phase 1b trial was a randomized, double-blind, placebo-controlled design that enrolled 29 patients with RA. Twenty eight patients completed four weeks of treatment. The trial was conducted at six sites in the United States. Patients received either 100 mg or 200 mg ARRY-797 twice daily, or placebo. In addition, all patients were on a background of methotrexate and could receive certain NSAIDs (including COX-2 inhibitors), corticosteroids (low-dose), opioids/analgesics, aspirin, or acetaminophen. Patients were evaluated every seven days for improvement in clinical signs and symptoms according three measures: CRP levels (marker of inflammation), patient's assessment of arthritis pain (VAS score), and NTx levels (marker of bone remodeling).


Effects on Signs and Symptoms of Rheumatoid Arthritis: The CRP levels at the 200 mg BID dose of ARRY-797 showed a statistically significant decrease during the first three weeks of the study but returned to baseline on week four. Also, the patient's assessment of pain (VAS score) showed trends to decrease in the 200 mg BID arm. The NTx levels for both active arms separated from placebo by as much as 30 percent in the 100 mg arm and 50 percent in the 200 mg arm.


Safety, Tolerability and Pharmacokinetics: ARRY-797 was well-tolerated through 29 days of dosing. There were no premature discontinuations for serious AEs in any of the study arms. The most common AEs were generally mild or moderate and were not significantly different than placebo. Based upon a preliminary assessment, the exposure of ARRY-797 was consistent with previous studies in healthy volunteers, there were no apparent drug-drug interactions between methotrexate and ARRY-797, and no apparent food effect was observed.


ARRY-797 in Acute Pain


The efficacy of ARRY-797 previously was evaluated in two acute inflammatory pain trials in patients with post-surgical dental pain. ARRY-797 achieved its primary and secondary endpoints for analgesic efficacy and was well-tolerated in both trials.


In the first trial, the analgesic effect of 400 mg of ARRY-797, compared to placebo, was statistically significant based upon the primary endpoint of total pain relief over six hours post dose (p