ChemoCentryx Reports Positive Phase I Results For CCX168, A Novel C5aR Antagonist, At The Annual American College Of Rheumatology Meeting (ACR)

ChemoCentryx, Inc., announced favorable Phase I results for CCX168 at the Annual American College of Rheumatology Meeting (ACR). CCX168, the Company's orally-active small molecule antagonist, is designed to target the receptor for the pro-inflammatory protein known as 'complement 5a' (C5a), a so-called anaphylatoxin that drives inflammatory responses associated with autoimmune diseases such as vasculitis, aged-related macular degeneration, rheumatoid arthritis and related pathologies. Data from Phase I clinical trials showed that CCX168 exhibited an excellent safety profile, while producing greater than 90% receptor blockade of inflammatory cells in the blood throughout the day. Additionally, data from preclinical studies using transgenic mice (which express human C5aR) demonstrated robust efficacy of CCX168 in a vasculitis model. CCX168 is poised to enter Phase II clinical development for the treatment of patients with renal vasculitis.


These data were highlighted in poster presentations entitled:



-- "Phase 1 Clinical Safety, Pharmacokinetic and Pharmacodynamic Evaluation of the Novel C5aR antagonist CCX168, a Potential Therapeutic for ANCA-Vasculitis"



-- "The Human C5a Receptor (hC5aR) Antagonist CCX168 Effectively Ameliorates Symptoms in a Model of ANCA Glomerulonephritis (GN) in hC5aR Knock-in Mice"


"We are very pleased to report that CCX168 appears to be the first true orally-active small molecule C5aR antagonist drug ever advanced into the clinic," stated Thomas J. Schall, Ph.D., President and Chief Executive Officer of ChemoCentryx. "CCX168 has the ability to safely achieve far greater than 90% receptor coverage throughout the day. While other approaches have attempted, without success, to accomplish such an attractive pharmacokinetic behavior and safety profile, CCX168 may well be in a class by itself. We think that this new agent has extraordinary potential in treating previously intractable conditions such as the devastating vasculitis seen in autoimmune diseases."


CCX168 Study Results and ANCA-Associated Vasculitis


In Phase I clinical trials CCX168 was safe and well tolerated, with excellent oral bioavailability and dose-proportional exposure increases in human subjects. Pharmacokinetic and pharmacodynamic data indicated that 30 to 50 mg of CCX168 given orally twice daily in humans results in greater than 90% C5aR coverage in blood at all times, and this is considered optimal for CCX168 evaluation in Phase II trials in vasculitis.


Supporting the Phase I data are results from a mouse model of anti-neutrophil cytoplasmic autoantibody (ANCA) associated glomerulonephritis (GN). In this study, human C5aR transgenic mice were employed, and ANCA kidney disease was profoundly inhibited by doses of CCX168 that are very similar to those achieved safely in the human Phase I studies.















CCX168 is a highly potent and very selective compound that specifically targets the receptor for the anaphylotoxin designated C5a, a component of the body's complement system and a potent driver of the inflammatory response associated with ANCA-associated vasculitis and other autoimmune disease. In ANCA disease, auto-antibodies lead to the activation and increased adhesiveness of neutrophils to endothelial cells that line the interior surfaces of blood vessels in the kidney and other organs. These adhering neutrophils accumulate inside the blood vessels and initiate an inflammatory cascade. Activation of the complement pathway occurs as a consequence, with production of C5a, one of the most potent pro-inflammatory mediators of the complement system. C5a, through binding to its receptor C5aR, induces expression of additional adhesion molecules and chemotactic factors, thus perpetually amplifying the destructive inflammatory cascade. C5aR also mediates smooth muscle contraction, increasing vascular permeability and altering blood flow. If left untreated, ANCA-associated vasculitis may lead to renal and pulmonary failure and is often fatal. Current therapies include toxic treatments such as cyclophosphamide and high dose corticosteroids. Under an alliance between ChemoCentryx and GlaxoSmithKline's (GSK's) Center of Excellence for External Drug Discovery (ceedd), GSK has the right to exercise an option to license CCX168 after Phase II clinical trials.


Certain statements in this press release may constitute "forward-looking statements". These statements are made on the basis of current expectations, forecasts and assumptions that involve risks and uncertainties, including, but not limited to, economic, competitive, governmental and technological factors outside of our control, that may cause our business, strategy or actual results to differ materially from those expressed or implied. We do not intend, and undertake no obligation, to update any forward-looking statements, whether as a result of new information, future events or otherwise.


Source: ChemoCentryx, Inc

Bracelets can 'ease' arthritis pain

According to a new study, magnetic bracelets can ease pain and discomfort experienced by arthritis sufferers.


UK researchers, writing in the British Medical Journal, found a significant reduction in pain scores among 65 wearers with
arthritis and claim the bracelets reduced the amount of painkillers sufferers need to take.


The study by Professor Edzard Ernst and colleagues from the Peninsular Medical School, Exeter and Plymouth, also suggested
that the stronger the bracelet the greater the effect.


The researchers claim that the one-off cost of the bracelets, at ?30 to ?50, compares well with the cost of taking
painkillers in the long term.


However, studies with dummy versions of the bracelets produced mixed results, suggesting that they might have a placebo
effect.


The authors concluded: "We cannot be certain whether our data show a specific effect of magnets, a placebo effect, or both.
Whatever the mechanism, the benefit from magnetic bracelets seems clinically useful."


hda-online.uk/html/about/phnews.asp?ItemID=7345574

Secretary Of State Backs MS Society Work Retention Project

Secretary of State for work and pensions James Purnell MP is lending his support to an MS Society-led project designed to help people with chronic and fluctuating health conditions remain in work.


Mr Purnell joins the MS Society and a range of charities, work organisations and leading UK employers and trade unions at a round table event at the Work Foundation in London today (2 June).


Also attending is Dame Carol Black, author of 'Working for a healthier tomorrow' - the influential report that prompted the DWP to support the MS Society in setting up the project: 'Work retention for people with chronic and fluctuating health conditions'.


Simon Gillespie, chief executive of the MS Society, said: "All too often, people with multiple sclerosis (MS) and other fluctuating health conditions say they left work too soon, either voluntarily or due to pressure from an employer. We want to provide an information resource that can act as a safety net at the point at which someone's working life may be about to fall off a cliff.


"We also hear positive stories from employers who have invested in keeping on an employee with a chronic or fluctuating health condition. In many cases, they have benefited from keeping experienced staff on board, and have avoided the costs of recruiting anew. This information needs to be shared and we welcome the support of the Secretary of State and Dame Carol in pushing this up the work agenda."


This working group will act as the starting point for a project supported by the DWP, designed to bring together an online resource for employees and employers, raising awareness of the support available to help people to stay in work. The site is due to be launched by the end of 2009. The conditions specifically covered by the project are MS, diabetes, rheumatoid arthritis, HIV and cancer.

Source
MS Society

Max daily OTC dose of acetaminophen shows efficacy comparable to Rx doses of naproxen for OA pain

Researchers today announced new clinical evidence showing that long-term use of maximum recommended over-the-counter (OTC) daily doses of acetaminophen (APAP) provide efficacy comparable to prescription doses of naproxen (NAP) for the management of mild-to-moderate osteoarthritis (OA) pain of the hip or knee.


Preliminary analyses of the multicenter, randomized, double-blind, parallel-group, comparative study involving 551 patients aged 40 to 75 years old with mild-to-moderate OA of the hip or knee were presented during the 2nd Joint Scientific Meeting of the American Pain Society and the Canadian Pain Society. Patients in the APAP-treated group (n=276) received 4000mg per day, while those in the NAP group (n=275) received 750 mg per day. All patients were evaluated at one-, three-, and six-month intervals for pain, stiffness, and physical function using the WOMAC™* subscale for pain.


"Even out to six months, our analyses showed no statistical differences between the efficacy of acetaminophen and naproxen for the management of osteoarthritis pain of the hip and knee," said Dr. Anthony Temple, VP Medical Affairs, McNeil Consumer & Specialty Pharmaceuticals. "These results indicate that acetaminophen is as effective as prescription doses of naproxen for the pain of arthritis when administered for up to 6 months under the care and observation of the physician."


*Western Ontario and McMaster Universities osteoarthritis index: a standard methodology to measure osteoarthritis pain relief.


About Osteoarthritis


Osteoarthritis is the most common form of arthritis in the United States, affecting more than 20 million Americans. Joint pain and stiffness due to OA results from the breakdown of cartilage in joints. The most commonly affected areas affected by OA are the fingers, knees, hips, and spine. Other joints affected less frequently include the wrists, elbows, shoulders, and ankles.


The American College of Rheumatology's "Recommendations for the Medical Management of Osteoarthritis of the Hip and Knee: 2000 Update" urge OA sufferers to begin treatment with non-medical remedies such as exercise and weight control. Acetaminophen is listed as a first-line medical treatment for osteoarthritis.



The American College of Rheumatology is an independent, professional medical and scientific society that does not guarantee, warrant or endorse any commercial product or service.



Contact: Ami Schmitz-Levine

215-273-8162

D. J. Storch & Associates Inc.

Physical Therapy Can Help Relieve Boomers' Back Pain

Because of
increasingly demanding jobs, hectic daily schedules, participating in
recreational activities, and caring for children, grandchildren, and
elderly parents, back pain is becoming a common thread among baby boomers.
However, this generation is less resigned to simply accept the changes
brought about by aging, says the American Physical Therapy Association
(APTA).



Baby boomers, those born between 1946 and 1964 and who now make up one
fourth of the U.S. population, are leading more active lifestyles than
previous generations. "Baby boomers are as active as they were when they
were younger, but now they're living with chronic low back pain or
osteoarthritis," says Jennifer Gamboa, PT, DPT, OCS, MTC, owner of Body
Dynamics, a physical therapy private practice in Arlington, VA. "These
conditions as well as others can benefit greatly from physical therapy
intervention."



Back pain among baby boomers will be the subject of a toll-free
national hotline on Thursday, February 15, from 9:00 am until 5:00 pm,
Eastern Standard Time, sponsored by the American Physical Therapy
Association's Orthopaedic and Sports Physical Therapy Sections. Physical therapists will be
on hand to answer questions about injury prevention, exercise, and ways to
prevent back pain. The hotline is offered as a public service to help
people learn how to minimize back pain and is not a substitute for a visit
to a physical therapist or other health care professional.



"Frequently, patients may unknowingly exacerbate their pain by
exercising improperly or by having poor posture," Gamboa said. Physical
therapists can help to identify and correct those behaviors. Physical
therapists work on increasing muscle strength and cardiovascular endurance,
restoring and improving range of motion in joints, and decreasing muscle
and joint pain.




Physical therapy interventions may include therapeutic exercise, manual
therapy, and functional training, as well as exercises for strength,
flexibility, and range of motion, and devices designed to rest or support
the joint, such as orthotics or splints. "The goal of a physical therapist
is to get you back to doing what you enjoy on a daily basis with as little
discomfort as possible."



For those patients who either are just starting an exercise regime, or
for injured weekend warriors just getting back in the game, Gamboa
recommends starting off slowly and not doing too much too fast. She notes
that physical therapists devise step-wise plans in order for patients to
gain strength and mobility.



Gamboa also suggests investing in an ergonomically correct chair for
work, taking frequent breaks from computers, and participating in
stress-relieving activities, such as yoga or meditation, to offset back
pain.



Physical therapists (PTs) are health care professionals who diagnose
and treat individuals of all ages, from newborns to the elderly, who have
medical problems or other health-related conditions that limit their
abilities to move and perform functional activities in their daily lives.
PTs examine each individual and develop a plan of care using treatment
techniques to promote the ability to move, reduce pain, restore function,
and prevent disability.



The American Physical Therapy Association (apta) is a
national organization representing nearly 70,000 physical therapists,
physical therapist assistants, and students nationwide. Its goal is to
foster advancements in physical therapist education, practice, and
research. Consumers can access "Find a PT" to find a physical therapist in
their area, as well as physical therapy news and information at
apta/consumer.


American Physical Therapy Association

apta/

Can-Fite Completed Patient Enrollment For The Confirmatory Phase IIb Trial In Rheumatoid Arthritis Patients With CF101

Can-Fite BioPharma (TASE:CFBI), a biotechnology company traded on the Tel Aviv Stock Exchange has achieved yet another goal by completion of enrollment of 230 patients in its confirmatory phase IIb RA trial. Approximately 230 patients were enrolled to this study, randomized into 3 groups treated with 0.1 mg and 4 mg of CF101, and placebo. Patients are taking the drug for 12 weeks plus 2 weeks of follow-up. The trial is being conducted in 30 sites in Europe and Israel. The company estimates to release study data on H1 2009.


In addition, the company recently announced that it has signed an out license agreement with Kwang Dong Pharmaceutical Co., a Korean company, granting Kwang Dong exclusive rights to develop and commercialize the drug CF101 for rheumatoid arthritis, in Korea. CF101, Can-Fite's lead drug, is currently being tested in a multi-national Phase IIb study for its therapeutic activity in the treatment of rheumatoid arthritis and in two Phase IIa studies: one for the treatment of psoriasis and the other for dry eye syndrome.


The terms of the license include an upfront payment as well as milestone payments to Can-Fite in an aggregate amount of US$ 1.5M; and certain royalties on sales. Additionally, Kwang Dong will also purchase equity in Can-Fite in an amount representing 1% of Can-Fite's outstanding share capital at a premium of 50% above market price.


CAN-FITE BIOPHARMA LTD is a public company traded on the Tel Aviv Stock Exchange. The Company, which commenced business activity in 2000, was founded by Prof. Pnina Fishman, an investigator from Rabin Medical Center, and patent attorney Dr. Ilan Cohn, a senior associate at Reinhold Cohn Patent Attorneys. Prof. Pnina Fishman serves as the CEO of Can-Fite. The Company was founded on the basis of scientific findings made by Prof. Pnina Fishman and focuses on the development of molecule-based drugs that bind to receptors of cancerous or inflammatory cells and inhibit their development.


Can-Fite's development pipeline currently has two drugs: CF101 and CF102. The company is simultaneously conducting several preclinical and clinical trials with the two drugs for various indications. CF101 is being studied for the treatment of rheumatoid arthritis (Phase IIb), dry eye syndrome (Phase II) and psoriasis (Phase II). Can-Fite develops CF102 for the treatment of liver conditions, including liver cancer, hepatitis infections and liver tissue regeneration.


Source

Can-Fite BioPharma

Pnina Fishman, Ph.D.

Chief Executive Officer

canfite

9.5% Of American Adults Treated For Arthritis

Approximately 21 million Americans - 9.5 percent of adults 18 and older - either visited or called a doctor for a prescription to reduce arthritis pain in 2005, according to the latest News and Numbers from the Agency for Healthcare Research and Quality.


The most common form of arthritis is osteoarthritis. It is usually associated with aging and most often causes pain and stiffness in the fingers, knees, and hips. A less common form of arthritis is rheumatoid arthritis, occurring when the body's own defense system doesn't work properly, causing pain in the joints and bones. Rheumatoid arthritis may also affect internal organs and systems.


AHRQ's data found that in 2005:


-- Some 9.5 million adults sought treatment, but women did it more often than men - 12 percent vs.7 percent.


-- More whites sought treatment for arthritis (10.5 percent), followed closely by blacks (just under 10 percent), compared to Hispanics (6 percent), and Asians (4 percent).


-- About $32 billion was spent for arthritis treatments, which included doctor visits (36 percent), hospital care (31 percent), prescription drugs (21 percent), home health care (12 percent) and emergency room visits (less than 1 percent).


AHRQ, which is part of the U.S. Department of Health and Human Services, works to enhance the quality, safety, efficiency, and effectiveness of health care in the United States. The data in this AHRQ News and Numbers summary are taken from the Medical Expenditure Panel Survey, a detailed source of information on the health services used by Americans, the frequency with which they are used, the cost of those services, and how they are paid. For more information, go to Arthritis: Use and Expenditures among U.S. Noninstitutionalized Population, 2005.


ahrq

Joint Pain And Estrogen Deprivation

Recent evidence suggests caution in prescribing hormone therapy for breast cancer and sheds new light on "menopausal arthritis"


One of the most effective new treatments for breast cancer is a hormone therapy. Aromatase inhibitors work by powerfully blocking the conversion of androgen precursors into estrogens, which lowers estradiol levels in the bloodstream and estrogen levels in peripheral tissues. Because aromatase inhibitors reduce the rates of recurrence in women with early-stage postmenopausal breast cancer, these agents are not only becoming widely used in breast cancer treatment, but also being explored for their potential to prevent the disease in women at high risk. While focusing on this therapy's promise, advocates have tended to downplay one of its drawbacks. Women treated with aromatase inhibitors often experience joint pain and musculoskeletal aching--severe enough, in some cases, to make them stop the treatment.


Two noted researchers, David T. Felson, M.D., of Boston University Clinical Epidemiology Unit, and Steven R. Cummings, M.D., of California Pacific Medical Center Research Institute and University of California, San Francisco, have thoroughly examined the evidence linking aromatase inhibitors and, more broadly, estrogen deprivation joint pain. In the September 2005 issue of Arthritis & Rheumatism (interscience.wiley/journal/arthritis), they share their insights to alert oncologists, primary care physicians, and other health care professionals to this widely overlooked, potential problem for women.


"Estrogen's effects on inflammation within the joint are not well known," Dr. Felson and Dr. Cummings observe. Yet, as they note, estrogen has well-established tissue-specific effects on inflammatory cytokines. Estrogen's role in joint inflammation could account for the increased sensitivity to pain that some women suffer with estrogen depletion. Citing studies of pharmacological suppression of estrogen and studies of natural menopause, the authors offer a look at compelling evidence associating estrogen deprivation with joint pain, including:


# Aromatase inhibitors have been linked to higher rates of joint and muscle pain than tamoxifen and placebo in various clinical trials for breast cancer treatment and prevention. One example: In a National Cancer Institute of Canada study, 5,187 postmenopausal women who completed a 5-year course of tamoxifen therapy for breast cancer were randomized to a further 5 years receiving the aromatase inhibitor letrozole or a placebo. 21 percent of women taking letrozole reported joint pain compared with 16 percent of the women receiving placebo.















# In a study of leuprolide, a hormonal agent used to treat infertility and a variety of gynecological disorders, 102 premenopausal women experienced symptoms of estrogen deprivation, such as vaginal dryness, after 2 weeks of treatment, and suffered joint pain between weeks 3 and 7 of treatment. Overall, 25 percent of the women developed persistent joint pain, affecting the knees, elbows, ankles, and other areas, during the study. The pain was resolved in all women between 2 and 12 weeks after stopping the leuprolide therapy.


# In a postmenopausal estrogen/progestin intervention trial, women who received estrogen had a significantly decrease chance of musculoskeletal symptoms--between 32 and 38 percent--compared with women randomly assigned placebo. Symptoms reported in the placebo group included joint pain, muscle stiffness, and skull and neck aching. In other studies, however, estrogen replacement therapy had no beneficial effect on musculoskeletal pain.


Dr. Felson and Dr. Cummings also highlight recent data showing that Asian women undergoing menopause have lower estradiol levels than Caucasian women and seem to be more vulnerable to a syndrome commonly known as "menopausal arthritis." They also note the high rate of both osteoarthritis and rheumatoid arthritis in postmenopausal women. They conclude by stressing the need for further research into the contribution of estrogen deficiency to arthritis, as well as for recognizing the risks of musculoskeletal syndrome when prescribing aromatase inhibitors and other estrogen-depleting treatments.


Article: "Aromatase Inhibitors and the Syndrome of Arthralgias With Estrogen Deprivation," David T. Felson and Steven R. Cummings, Arthritis & Rheumatism, September 2005; 52:9; pp. 2594-2598.


John Wiley & Sons, Inc.

interscience.wiley


View drug information on Estradiol Transdermal System.

Paracetamol may be better for osteoarthritis pain than anti-inflammatories

According to researchers at Queensland University, Australia, paracetamol might be better for patients with
osteoarthritis (who suffer chronic pain) than anti-inflammataries.


Lead researchers, Dr M Yelland, and team, carried out a 12-week trial with 70 patients (all had osteoarthritis and suffered
chronic pain). Half of the patients were on paracetamol while the other half were on non-steroidal anti-inflammatories. The
results showed that many patients experienced better relief with paracetamol.


The team said it is important for the patient to change the way he/she manages his/her pain.


Dr Yelland suggests that patients try out both pain killers with their doctors - have a mini trial and see what the results
are.

Genetic Research Related To Disabling Form Of Arthritis

Work done in part by researchers at The University of Texas Health Science Center at Houston has led to the discovery of two new genes that are implicated in ankylosing spondylitis (AS), an inflammatory and potentially disabling disease. In addition, the international research team pinpointed two areas along stretches of DNA that play an important role in regulating gene activity associated with the arthritic condition.



The findings, a critical milestone in the understanding of AS, are published in the January issue of Nature Genetics, a journal that emphasizes research on the genetic basis for common and complex diseases. "This helps us better understand what is driving this disease and gives us direction for new treatments and diagnostic tests," said John D. Reveille, M.D., the study's principal investigator and professor and director of the Division of Rheumatology and Clinical Immunogenetics at The University of Texas Medical School at Houston.



Reveille, the university's Linda and Ronny Finger Foundation Distinguished Chair in Neuroimmunologic Disorders, and Matthew A. Brown, M.D., professor of immunogenetics at Australia's University of Queensland, led the research by the Triple "A" Spondylitis Consortium Genetic Study (i.e. the TASC or Australo-Anglo-American Spondylitis Consortium). Based on work from a genome-wide association scan, the team identified genes ANTXR2 and IL1R2 as well as two gene deserts, segments of DNA between genes on chromosomes 2 and 21 that are associated with ankylosing spondylitis. Importantly, the study also confirmed the Triple "A" Australo-Anglo-American Spondylitis Consortium's previously reported associations of genes IL23R and ERAP1, formerly known as ARTS1.



Reveille, chief of rheumatology at Memorial Hermann-Texas Medical Center, said the genetic discoveries bring the scientific community closer to fully understanding AS, a chronic form of arthritis that attacks the spine and also can target other joints and organs in the body. The Centers for Disease Control and Prevention for the National Arthritis Data Workgroup estimates that AS and its related diseases affect as many as 2.4 million people in the United States. It generally strikes patients in their teens, 20s or 30s and can cause a complete fusion of the spine, leaving patients unable to straighten and bend.



Steve Haskew, who has lived with AS for more than three decades, said these genetic discoveries offer hope to patients, especially those newly diagnosed.



"When I first started experiencing lower back pain and the aching joints, no one could tell me what was wrong," said Haskew, co-leader of an AS support group. "It's fascinating to see how far we've come and how much has been learned about the disease."



Laurie Savage, co-principal investigator and executive director of the Spondylitis Association of America (SAA) said, "These new breakthroughs are, indeed, good news for those whom we serve. It is very encouraging to know that the health impact and economic consequences of spondyloarthritis in the world eventually will be contained as a direct consequence of the dedication of Drs. Reveille, Brown and colleagues, and that of the many individuals affected by spondyloarthritis who have participated in these studies."



The study, titled "Genomewide association study of ankylosing spondylitis identifies multiple non-MHC susceptibility loci," was supported in part by two grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Other study contributors from the UT Health Science Center at Houston are research associates Laura Diekman and Rui Jin and Xiaodong Zhou, M.D., associate professor of medicine.



Source:
Meredith Raine


University of Texas Health Science Center at Houston

Canakinumab (ACZ885), A New Biological Drug In Development, Shows Potential In Treating The Most Severe Form Of Arthritis In Children

Canakinumab (ACZ885), a fully human monoclonal antibody currently in development to treat a wide range of autoinflammatory diseases, has been shown to rapidly control the disease's symptoms in children affected by Systemic Juvenile Idiopathic Arthritis (SJIA)1 with fever and arthritis, a kind of juvenile arthritis where interleukin-1 plays a pivotal role in the majority of patients causing inflammation and tissue destruction.


The results were presented today at the 15th Pediatric Rheumatology European Society Congress (PRES) in London and indicate that canakinumab could provide a major therapeutic advance in the treatment of this pediatric inflammatory disorder.


These preliminary data from the Phase I/II study showed more than half of the young patients treated with canakinumab achieved at least 50% control of the disease's symptoms within 15 days. In addition, four patients achieved complete remission of the disease i.e., no arthritis-inflammation in joints, no fever, and no disease activity according to the physicians' assessment1.


SJIA is the most severe form of childhood arthritis, characterized by destructive arthritis, fever and rash. Suboptimal treatment can lead to growth retardation, joint and bone disability, as well as serious developmental and social consequences for these young patients4,5. In severe cases, children affected by SJIA can suffer from significant life-threatening complications such as the so-called "Macrophage Activated Syndrome", mostly due to infections and requiring immediate intensive care6.


"There is an immediate need for improved treatments that give rapid and sustained relief from the debilitating and distressing symptoms experienced by children with SJIA," said Nicolino Ruperto, MD, MPH, Senior Scientist of the Pediatric Rheumatology International Trial Organization (PRINTO), Istituto Gaslini, Genoa, Italy. "These preliminary data show the significant potential of canakinumab to provide rapid and long-lasting efficacy that can transform the lives of our patients and their families."


Canakinumab is also being investigated in a Phase III study for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), a group of rare but serious life-long diseases including Muckle Wells Syndrome. The Phase II data presented earlier this year demonstrated that CAPS patients treated with canakinumab, after one single dose, achieved complete and long-lasting clinical remission which lasted 115 days on average2,3.


Additional data presented at PRES Congress reinforced the potential of canakinumab to treat CAPS in children. In fact, in young patients aged between four and 17 years, after one single dose, canakinumab was shown to provide long-lasting remission of symptoms of inflammation for an average of close to 90 days7.















Canakinumab is human monoclonal antibody. Unlike other agents, it blocks solely interleukin 1?? (IL-1??), one form of the interleukin-1 protein that causes the body to 'attack' itself in inflammatory diseases.


The Phase I/II study results presented in London involved 19 children with SJIA aged between four and 19 years, who presented with fever, at least two inflamed joints, and all signs of the systemic inflammation. The study participants received a single subcutaneous injection of canakinumab dosed at 0.5 - 9 mg per kilo, followed by an observation period and re-dosing upon relapse. Eleven of the 19 patients involved in the study responded to canakinumab quickly, an at least 50% improvement of their disease activity versus pre-treatment was observed within two weeks, four patients were even classified as disease-free. Treatment was well-tolerated, the most common adverse events were upper respiratory tract infection1.


SJIA is a form of Juvenile Idiopathic Arthritis (JIA). It is often difficult to manage and many patients suffer poor outcomes6. The disease is characterized by symptoms including daily spiking fever, muscle pain, severe rash and inflammation of major organs such as the heart, and lungs, and hepatosplenomegaly7-10. Unlike other forms of JIA, however, children with SJIA may not develop chronic arthritis until six months or even years after the initial onset of fever6. The term 'systemic' refers to the body being affected as a whole. During the course of the disease the systemic sign and symptoms (fever and rash) may disappear leaving the child just with arthritis; this second group of SJIA children has not been considered for inclusion if the Phase I/II study.


SJIA accounts for approximately 10% - 20% of all cases of JIA11 which occur in 30 - 150 per 100,000 children - a similar incidence to juvenile diabetes12. Up to 30% of children with SJIA will still have active disease after 10 years, and the incidence of death in this group is high4.


The potential of canakinumab is reflected in its broad development program. In addition to the Phase II study in SJIA and the Phase III study program in CAPS, canakinumab is also being investigated in more common inflammatory diseases such as rheumatoid arthritis (RA), which affects up to 1% of the world's population13. A study in RA currently underway uses an innovative tailored approach with biomarkers to predict response to treatment. If successful, this may give suitable patients a personalized approach to treating their disease.


Orphan drug status has already been granted to canakinumab in the European Union and US for the treatment of CAPS, and in the EU for SJIA. Orphan drugs are those designed to treat serious or life-threatening diseases affecting less than 200,000 people (in the US)14 or less than five out of 10,000 people (in the EU)15.


Disclaimer


The foregoing release contains forward-looking statements that can be identified by terminology such as "in development", "potential", "can", "being investigated", "could", "may", or similar expressions, or by express or implied discussions regarding potential marketing approvals for canakinumab or regarding potential future revenues from canakinumab. Such forward-looking statements reflect the current views of the Company regarding future events, and involve known and unknown risks, uncertainties and other factors that may cause actual results with canakinumab to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that canakinumab will be approved for sale in any market. Nor can there be any guarantee that canakinumab will achieve any levels of revenue in the future. In particular, management's expectations regarding canakinumab could be affected by, among other things, unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; unexpected regulatory actions or delays or government regulation generally; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry and general public pricing pressures, and other risks and factors referred to in Novartis AG's current Form 20-F on file with the US Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.


About Novartis


Novartis AG provides healthcare solutions that address the evolving needs of patients and societies. Focused solely on healthcare, Novartis offers a diversified portfolio to best meet these needs: innovative medicines, cost-saving generic pharmaceuticals, preventive vaccines, diagnostic tools and consumer health products. Novartis is the only company with leading positions in these areas. In 2007, the Group's continuing operations (excluding divestments in 2007) achieved net sales of USD 38.1 billion and net income of USD 6.5 billion. Approximately USD 6.4 billion was invested in R&D activities throughout the Group. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 98,000 full-time associates and operate in over 140 countries around the world. For more information, please visit novartis.


References


1. Ruperto, N et al. A phase II trial with canakinumab, a new IL-1?? blocking monoclonal antibody (ACZ885), to evaluate preliminary dosing, safety and efficacy profile with systemic Juvenile Idiopathic Arthritis (sJIA), oral presentation at PReS Congress, September 15 2008, London, England.


2. Lachmann H.J. et al. Treatment of cryopyrin associated periodic fever syndrome with a fully human anti-IL-beta monoclonal antibody (ACZ885): results from a subcutaneous administration study, oral presentation at FMFSAID, April 8 2008, Rome, Italy.


3. Kuemmerle-Deschner J.B. et al, Long lasting response to ACZ885 in patients with Muckle-Wells Syndrome, oral presentation at FMFSAID, April 8 2008, Rome, Italy.


4. Ravelli, A. Martini, A. Juvenile idiopathic arthritis. Lancet. 2007 Mar 3;369(9563):767-78.


5. Woo, P. Systemic juvenile idiopathic arthritis: diagnosis, management, and outcome. Nat Clin Prac Rheumatology 2006; 2:1 28-34.


6. Illowite NT. Current treatment of juvenile rheumatoid arthritis. Pediatrics. 2002; 109-115.


7. Kuemmerle-Deschner J., et al.ACZ885 (canakinumab), a new IL-1 beta blocking monoclonal antibody provides long-lasting remission in children with Cryopyrin Associated Periodic Syndrome (CAPS), oral presentation at PRES Congress, September 16 2008, London, England


8. Illowite, NT. Systemic Juvenile Idiopathic Arthritis - A 2006 Update. Medscape. Available at:. medscape/viewarticle/540239_2. Last accessed on August 22, 2008.


9. Lomater C, Gerloni V, Gattinara M, et al. Systemic onset juvenile rheumatoid arthritis: a retrospective study of 80 consecutive patients followed for 10 years. J Rheumatol. 2000; 27:491-496.


10. Wallace CA, Levinson JE. Juvenile rheumatoid arthritis: outcome and treatment for the 1990's. Rheum Dis Clin North Am. 1991; 17:891-905.


11. Ansell BM, Wood PN. Prognosis in juvenile chronic polyarthritis. Clin Rheum Dis. 1976; 2:397-412.


12. Petty RE, Southwood TR, Baum J et al Revision of the Proposed Classification Criteria for Juvenile Idiopathic Arthritis: Durban, 97 Journal of Rheumatology 1998; 25:1991-1994.


13. Andersson Gare B. Juvenile arthritis -who gets it, where and when? A review of current data on incidence and prevalence. Clin Exp Rheumatology 1999; 17: 367-74.


14. fda/orphan. Last accessed August 22, 2008.


15. ec.europa.eu/health/ph_threats/non_com/rare_6_en.htm. Last accessed August 22, 2008.

Novartis

U.S. Senate Passes Psoriasis Resolution Calling For Improved Research And Access To Care

The U.S. Senate passed Senate
Resolution 420 (S. Res. 420), a bipartisan resolution calling for
improvements in treatment and access to care for individuals with psoriasis
and psoriatic arthritis. Sen. Gordon Smith, R-Ore., lead sponsor of the
resolution, is a dedicated champion for the psoriasis community and worked
to ensure passage of the measure prior to Psoriasis Awareness Month in
August.


Sen. Frank Lautenberg, D-N.J., joined Smith in leading the effort; they
were supported by Sens. Tim Johnson, D-S.D., Robert Menendez, D-N.J., Rick
Santorum, R-Pa., John Warner, R-Va., and Ron Wyden, D-Ore.


The resolution recognizes that psoriasis and psoriatic arthritis can be
painful, debilitating diseases that can significantly and adversely impact
quality of life. Millions of people hold misconceptions about psoriasis,
and it remains an often misunderstood disease. The resolution draws
much-needed attention to the seriousness of psoriasis, the importance of
early diagnosis and proper treatment, and the need for public awareness
about psoriasis.


Through passage of the resolution, the U.S. Senate is encouraging the
federal government to expand its psoriasis research efforts, including the
psychological and physical effects of the disease. The Senate resolution
also supports efforts to increase access to treatments for individuals
living with psoriasis and psoriatic arthritis. The National Psoriasis
Foundation will work with members of Congress and federal research agencies
to ensure that the intent of the resolution is carried out.


"The National Psoriasis Foundation applauds today's Senate passage of
an important resolution seeking to improve psoriasis research and access to
care," said Gail M. Zimmerman, president and CEO of the National Psoriasis
Foundation. "According to the National Institutes of Health, as many as 7.5
million Americans live with psoriasis. Thanks to the leadership of Senators
Smith and Lautenberg, the need to boost psoriasis research and access to
care has been elevated at the highest level of government."


Passage of S. Res. 420 is part of a comprehensive federal legislative
agenda being pursued in Washington, D.C., by the Psoriasis Foundation. The
Psoriasis Foundation is also advocating passage of a resolution in the
House of Representatives that is similar to the Senate resolution. The
House resolution (H. Con. Res. 340) urges expansion of genetic, clinical
and basic research focused on increasing understanding of the causes of
psoriasis and psoriatic arthritis. It also calls for the Secretary of
Health and Human Services to convene a special panel to study the
availability of treatments for individuals with psoriasis and psoriatic
arthritis.


About Psoriasis


Psoriasis is a noncontagious, genetic disease of the immune system that
results when faulty signals in the immune system prompt skin cells to
regenerate too quickly, causing red, scaly lesions that can crack and
bleed. It often affects the elbows, knees, scalp and torso but can appear
anywhere on the body. As many as 7.5 million Americans have psoriasis,
according to the National Institutes of Health. Ten percent to 30 percent
of people with psoriasis also develop psoriatic arthritis, an inflammatory
disease which causes pain, stiffness and swelling in and around the joints.
Psoriasis can affect anyone at any age, including children. There is no
cure yet for this lifelong disease.


About the National Psoriasis Foundation


The National Psoriasis Foundation is the leading patient-driven,
nonprofit organization dedicated to improving the quality of life of people
who have psoriasis or psoriatic arthritis. We focus on education, advocacy
and research toward better treatments and a cure. For more information,
please call the Psoriasis Foundation, headquartered in Portland, Ore., at
800-723-9166 or visit psoriasis/.


The National Psoriasis Foundation

psoriasis/

Oily Fish Can Protect Against RA, But Smoking And Psychosocial Stress Increase Its Risk

Results from the EIRA study



New data presented at EULAR 2008, the Annual Congress of the European League Against Rheumatism in Paris, France, show that intake of oily fish is associated with a reduced risk of developing rheumatoid arthritis (RA), whereas psychosocial work stress and smoking can increase the risk of developing the condition. The findings, all taken from a large population-based case-control study in Sweden called EIRA (Epidemiological Investigation of Rheumatoid Arthritis), shed light on the important role of environmental and social factors in the development of RA.



Intake of Oily Fish



For the first time, the intake of oily fish has been demonstrated to have a protective effect against the development of RA, reducing an individual's risk by 20-30%. Studying 1,899 subjects with a confirmed diagnosis of RA (fulfilling ACR criteria) and 2,145 controls (randomly selected and matched for age, sex and residential area), investigators concluded that the odds ratio (OR) for developing RA was 0.8 (0.7-1.0) for those who consumed oily fish 1-7 times per week or 1-3 times per month, compared with those who never, or seldom consumed oily fish. Interestingly, no significant association with RA risk was observed for consumption of fish oil supplements.



Smoking Dosage



Tobacco smoking is an established risk factor for RA, but the investigators found that there is a dose dependency for the level of smoking (i.e. the number of cigarettes smoked across a given period) on the odds ratio of developing anti-citrulline (anti-CCP) positive RA. The highest odds ratios were seen in those carrying a risk variant of the susceptibility gene PTPN22. In the study, 1,240 cases and 798 controls were identified as smokers from a total group of 1,419 cases and 1,674 controls via an extensive questionnaire regarding lifestyle factors, including smoking habits.



These subjects were then classified into three different groups according to the number of pack years smoked - less then 10, 10-20 or more than 20 pack years (where one pack-year is equivalent to having smoked one pack per day for one year) and genotyped to determine the presence of the PTPN22 risk allele.



Psychosocial Stress at Work



Psychosocial stress at work, defined as low decision latitude (or low level of control) was found to be associated with a higher risk for RA. Collected via a validated questionnaire, this was demonstrated in both self-reported data (OR=1.6 (95% CI 1.2-2.2)) and JEM (job exposure matrix)-derived data (OR=1.3 (95% CI 1.0-1.7)). These results were only marginally changed when the investigators adjusted the odds ratios for social class and smoking for the 1,221 cases and 1,454 controls who participated in the study.



Mrs Annmarie Wesley of the Institute of Environmental Medicine, Stockholm, Sweden, EIRA investigator and lead author of the oily fish intake study, commented: "The findings from these studies add to an increasing body of evidence to support the assertion that lifestyle modifications can have a significant impact on an individual's risk for developing RA, one of the most common autoimmune diseases, affecting approximately 1% of adults worldwide. We hope that the data will contribute to the growing understanding of the aetiology of RA and, ultimately, its treatment and prevention"




















Abstract numbers: FRI0034, FRI0054 and SAT0129AHP



About EULAR
The European League Against Rheumatism (EULAR) is the organisation which represents the patient, health professional and scientific societies of rheumatology of all the European nations.


The aims of EULAR are to reduce the burden of rheumatic diseases on the individual and society and to improve the treatment, prevention and rehabilitation of musculoskeletal diseases. To this end, EULAR fosters excellence in education and research in the field of rheumatology. It promotes the translation of research advances into daily care and fights for the recognition of the needs of people with musculoskeletal diseases by the governing bodies in Europe.


Diseases of bones and joints, such as rheumatoid arthritis and osteoarthritis cause disability in 4 - 5 % of the adult population and are predicted to rise as people live longer.


As new treatments emerge and cellular mechanisms are discovered, EULAR 2008 brings together more than 12,000 experts - scientists, clinicians, healthcare workers, pharmaceutical companies and patients - to share their knowledge in a global endeavour to challenge the pain and disability caused by musculo-skeletal disorders.


To find out more information about the activities of EULAR, visit: eular/

Source: Rory Berrie / Camilla Dormer


European League Against Rheumatism

Confusion Over Safety Of NSAIDs For Pain Relief Leads Patients To Suffer In Silence

Confusion and concern about the benefits and safety hazards of painkilling drug treatments is leading many people with chronic musculoskeletal pain to try and manage their pain without any medication at all, a new global survey suggests.


The Arthritis Action Group (AAG), an organisation of physicians and researchers, surveyed perceptions of 1204 people with chronic musculoskeletal pain, many of whom suffer from arthritis, and 604 primary care physicians (PCPs), in six countries - UK, Germany, Italy, France, Mexico and Australia.


Presenting the "Insights into Pain Relief" survey results in Amsterdam during the annual EULAR rheumatology meeting, AAG Chairman Professor Anthony Woolf said the findings helped explain why so many people were still enduring pain without seeking medical advice or were putting up with inadequate pain relief. "Something needs to be done to change attitudes because pain greatly impairs quality of life", he said.


More than a million people in Europe have chronic pain with 4 out of 5 experiencing it constantly, he noted. One in four finds it puts a major strain on relationships, 60 per cent are unable to work and one in five lose their jobs. Poor pain management causes 500million working days to be lost each year in Europe at a cost of ?34 billion.


Confused


Almost two thirds of people surveyed (64%) said they were confused about what to take for pain relief because of conflicting information on drug safety that has emerged following the withdrawal of Vioxx (rofecoxib), a COX-2 selective non-steroidal anti-inflammatory drug (NSAID) . Around 4 out of 5 (78%) said they didn't know enough about the risks and benefits of medicines, whether prescribed or bought over-the-counter. Almost half (47%) said they weren't using any painkiller medication at all for a number of reasons. Some were concerned about side effects, often after reading worrying news stories about painkillers, some had been advised to stop medication by their PCP and some thought they could manage without them.


In many cases patients keep their concerns to themselves. Less than half had discussed with their doctor whether or not their treatment was working or providing benefits. Even fewer - only 30 per cent - had discussed potential risks or side effects and about the same proportion had discussed how to use painkillers effectively with regard to dosing and how often they are taken.


The survey also revealed a mismatch between doctors' and patients' perceptions. Whilst up to 48 per cent of patients are concerned about potential side effects of OTC painkillers, the same was true of only 14 per cent of physicians. One in four physicians found it difficult to communicate the risks and benefits of different pain medications. And nine out of 10 reported time constraints preventing them from giving advice.


Recent large meta-analyses of clinical trials have suggested standard doses of COX-2 and non-selective NSAIDs carry the same level of risk of increasing susceptibility to cardiovascular events. COX-2 selective NSAIDs however are less likely than traditional NSAIDs to cause ulcers in the upper or lower gastro-intestinal tract. Large randomised clinical trials, in progress or about to begin, will confirm this.


New ways of explaining simply the relative risks and benefits of treatment are required, said Dr Andrew Moore, Director of Research at the Pain Research Unit, Oxford University. A visual means, such as the Paling Risk Perception Scale, showing patients the magnitude of risks of experiencing serious side effects from medication alongside risks of a similar magnitude eg, being involved in an automobile accident, might help patients put risks and benefits into context, he suggested.


Currently, more than 30 million patients use NSAIDs every day. " All treatments contain some risk of adverse as well as beneficial effects and it is important for doctors and patients to discuss suitable treatments to ensure patients receive optimal care", he concluded.



By Olwen Glynn Owen

glynnowen macline



View drug information on Vioxx.

NICE Admits Previous Guidance Around Sequential Use Of Anti-TNF Therapies In Rheumatoid Arthritis Unfair

The National Institute of Health and Clinical Excellence (NICE) has today published findings of its appeal panel around the use of adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis (RA) after failure of a previous TNF-?± inhibitor (sequential use), deciding their previous guidance had been 'unfair' and 'perverse'1.


Within a 24 page document, published today on the Institute's website, the appeal panel (which included Sir Michael Rawlins, chairman of NICE) upheld numerous appeal points around the previously issued Final Appraisal Document (TA130). These included decisions around the Institute failing to act fairly and in accordance with its published procedures and preparing guidance that is perverse in light of the evidence submitted.


"The panel's decision to uphold these appeal points is very good news for thousands of rheumatoid arthritis patients ", explained Dr Brian Muller, Medical Director, Schering-Plough UK and Ireland, "In effect, NICE has returned some flexibility for Rheumatologists in the UK to make prescribing decisions about anti-TNF therapies based on both clinical and cost effectiveness grounds. We believe the NICE Appeal Panel have reached the right decision, and look forward to participating fully in any future appraisal".


He continued, "As we have consistently stated, Schering-Plough believes that, based on the supporting evidence, all patients should have the right to access the anti-TNF therapy their clinician feels is most effective for them, at whatever stage of their treatment pathway is deemed clinically appropriate. We hope the Appraisal Committee and the Institute will take every possible step to complete a re-appraisal as quickly and as efficiently as possible".


NICE has written to the Department of Health to seek advice about next steps around re-appraising sequential use of anti-TNF therapies for the treatment of RA. In the interim, all previous guidance around the sequential use of these medicines is now obsolete and should not be used by any healthcare professionals / prescribing advisors in making treatment decisions for patients with RA.



Further information about the NICE appeal is available online here.



-- An Appeal Panel was convened on 29th September 2008 to consider an appeal against the Institute's Final Appraisal Determination, to the NHS, on the use of adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis after failure of a previous TNF-?± inhibitor (sequential use).



-- The Panel considered appeals submitted by:

- Abbott Laboratories

- Arthritis and Musculoskeletal Alliance

- National Rheumatoid Arthritis Society

- Royal College of Nursing

- Schering Plough

- Wyeth Pharmaceuticals


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



References


1. NICE - Rheumatoid Arthritis Adalimumab Appeal Pane lDecision. (PDF), accessed 24 November 2008


schering-plough

Women Who Consume Large Amounts Of Tea Have Increased Risk Of Rheumatoid Arthritis

Women who drink tea have an increased risk of developing Rheumatoid Arthritis (RA) compared with those who drink none (p=0.04), according to results presented at EULAR 2010, the Annual Congress of the European League Against Rheumatism in Rome, Italy. Further results from the same study showed no correlation between the amount of coffee consumption and RA incidence (p=0.16).



The results of the US based longitudinal cohort study involving 76,643 women showed a positive association of incident RA in tea drinkers with an increasing Hazard Ratio (HR) observed alongside tea consumption (p=0.03). Consuming any amount of tea carried a significant risk of developing RA (HR 1.40 (95%CI 1.01-1.93) p=0.04) and women who drank ?‰?4 cups of tea per day had an increased risk of developing RA compared to those who drank none (HR 1.78 (95%CI 0.83-3.82)). An analysis of the method of preparation of coffee (filtered vs unfiltered) and presence or lack of caffeine in the beverage did not show any significant associations with RA or Systemic Lupus Erythematosus (SLE, an autoimmune disease in which the immune system harms the body's own healthy cells and tissues) (RA: filtered p=0.08, unfiltered p=0.38, SLE: filtered p=0.74, unfiltered p=0.97). No increase was shown in the risk of developing RA in participants who drank coffee compared to those that did not (RA: HR 1.09 (95%CI 0.77-1.54 p=0.63).



"We set out to determine whether tea or coffee consumption, or the method of preparation of the drinks was associated with an increased risk of RA or SLE - it is surprising that we saw such differences in results between tea and coffee drinkers," said Professor Christopher Collins, Assistant Professor of Medicine, Georgetown University Medical Center, Washington, USA. "This does make us wonder what it is in tea, or in the method of preparation of tea that causes the significant increase in risk of developing RA."



Data on women aged 50-79 were taken from the Women's Health Initiative Observational Study database (a major 15-year research program to address the most common causes of death, disability and poor quality of life in postmenopausal women) where participants completed a self-administered questionnaire providing information on daily consumption of coffee and tea.



The relationships between drinking tea and coffee and the risk of RA or SLE were assessed in age-adjusted models and in multivariate Cox proportional hazard models (a statustical approach to estimating survival data). At three years follow up, the diagnosis of incident RA was determined using self-reporting and respondent's feedback on use of disease modifying anti-rheumatic drugs (DMARDS). The variables studied in the RA population were also investigated in women with SLE, but no significant associations were found.



"These are very interesting findings and we hope that additional research will investigate this topic further. We do assert the need for caution in the interpretation of these findings as no strong causation effect has been confirmed, and encourage patients with rheumatic diseases to consult their physician before making any significant changes to their diet or caffeine intake" said Professor Paul Emery, President of EULAR and arc Professor of Rheumatology, Leeds Institute of Molecular Medicine, University of Leeds, UK



Abstract Number: FRI0108



Source: European League Against Rheumatism

Merck Did Not Misrepresent Data, Says Ex-CEO

According to Raymond Gilmartin, ex-CEO of Merck & Co., Merck did not withhold information about Vioxx's heart attack risks. After awarding a plaintiff $4.5 million, a New Jersey jury has to decide whether Merck should pay punitive damages.


Gilmartin took the stand and said 'The answer is definitely no.' after the plaintiff's lawyer, Mr. Lanier, asked him whether Merck had withheld or misrepresented data. According to Gilmartin, preliminary data gave no indication of a significant link between Vioxx and heart attack risk (or cardiovascular risk).


When Lanier referred to a 2000 study which showed Vioxx consumption made it five times more likely a patient would have a heart attack than Naproxen (another drug it was being compared to), Gilmartin said Naproxen was thought of as a drug that might provide cardiovascular protection - so obviously, the difference would be great (the meaning being, that if Vioxx had been compared to a drug with neutral effect on the heart, the difference in heart attack risk would not have been so great).


Gilmartin later explained that this was the reason the study which compared Vioxx to Naproxen was never sent to the FDA because Naproxen, being a drug that might protect the heart, would skewer the study. So they left it out of the report to the FDA.


Gilmartin was CEO and Chairman of Merck from 1994 to 2005. He was at the helm when Vioxx was launched, and also when it was withdrawn. In New Jersey punitive damages cannot total more than five times the amount awarded in compensation - so, the punitive damages will not be more than ?22.5 million.


Written by:




View drug information on Vioxx.

International ACTEMRA Rheumatoid Arthritis Study Highlighted In The Lancet

Patients with rheumatoid
arthritis treated with Roche's ACTEMRA(TM) (tocilizumab) experienced
significant and rapid reduction in the signs and symptoms of their disease,
according to a study published in this week's issue of The Lancet. Results
from the OPTION (TOcilizumab Pivotal Trial in Methotrexate Inadequate
respONders) trial -- a Phase III international study -- demonstrated that
RA patients achieved greater improvement of symptoms and a higher
quality-of-life with ACTEMRA, an interleukin-6 (IL-6) receptor inhibitor,
in combination with methotrexate, compared with methotrexate plus placebo.


"Results of this pivotal study convincingly demonstrate that
tocilizumab can effectively and rapidly diminish the painful and
debilitating effects of rheumatoid arthritis," said Josef Smolen, M.D.,
lead investigator of the OPTION trial and Professor of Medicine at the
Department of Internal Medicine at the Medical University of Vienna,
Austria. "These trial findings are significant because we know that many
rheumatoid arthritis patients continue to experience symptoms of joint
pain, stiffness, physical disability and fatigue, despite treatment with
existing therapies."



About OPTION Study



In the OPTION trial, a three-arm, double-blind, controlled Phase III
study, 623 patients were randomized to receive ACTEMRA intravenously
(either 4mg/kg or 8mg/kg) every four weeks plus methotrexate weekly or
placebo infusions plus methotrexate weekly. The study was conducted in 73
trial sites in 17 countries outside the United States.



At 24 weeks, 58.5% of ACTEMRA patients (8mg/kg) achieved a 20%
reduction in RA symptoms (ACR20)(1), compared with 26.5% of patients in
placebo plus methotrexate patients. In the study, 43.9% of patients treated
with ACTEMRA (8mg/kg) plus methotrexate achieved at least a 50% (ACR50)
reduction in symptoms compared to 10.8% of patients receiving placebo and
methotrexate; ACR70 was achieved in 22% of the treatment group versus 2% in
the control group. A rapid decrease in disease activity (DAS28)(2) was seen
as early as two weeks in a greater proportion of patients treated with
ACTEMRA plus methotrexate, with 27.5% achieving DAS28 less than or equal to
2.6 by 24 weeks.



Additionally, results showed that 80% of patients in the ACTEMRA
(8mg/kg) plus methotrexate group responded with moderate to good
improvements in RA symptoms, according to the EULAR response criteria(3),
compared with 35% for those treated with placebo and methotrexate at 24
weeks. ACTEMRA was generally well tolerated; the most common adverse events
reported more frequently in the ACTEMRA arms of the OPTION trial were upper
respiratory tract infection, nasopharyngitis and headache.
















The OPTION trial also assessed physical function and quality-of-life at
baseline and every four weeks thereafter. Patients receiving ACTEMRA
achieved significantly greater improvement in areas of fatigue and mental
function at 24 weeks, and achieved normal levels of hemoglobin and
C-reactive protein (CRP), a marker of inflammation due to RA, compared with
patients receiving placebo plus methotrexate.



"We are very encouraged by the findings of the study as they further
establish the role of ACTEMRA and its unique blockade of IL-6 receptors as
a potential new biologic treatment option for patients with RA," said Lars
Birgerson, M.D., Ph.D, Vice President, Global Head Medical Affairs, Roche.



About ACTEMRA(TM) (tocilizumab)



ACTEMRA is the first humanized interleukin-6 (IL-6) receptor-inhibiting
monoclonal antibody. 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 and relieve certain systemic effects of
RA. The extensive clinical development program conducted by Roche includes
five clinical studies and has enrolled more than 4,000 patients in 40
countries, including the United States. Three of these studies are
completed and have reported meeting their primary endpoints. Another Phase
III trial evaluating ACTEMRA in RA is an ongoing two-year study and is
expected to report one-year data evaluating the effect of ACTEMRA on the
inhibition of structural joint damage later this year. ACTEMRA is awaiting
approval in the United States and Europe.



ACTEMRA is part of a co-development agreement with Chugai, a Japanese
company. In June 2005, ACTEMRA was launched by Chugai in Japan as a therapy
for Castleman's disease; in April 2006, additional indications for
rheumatoid arthritis and systemic-onset juvenile idiopathic arthritis were
also filed in Japan and are currently under review.



The serious adverse events reported in ACTEMRA clinical trials were
serious infections and hypersensitivity reactions including anaphylaxis.
The most common adverse events reported in clinical studies were upper
respiratory tract infection, nasopharyngitis, headache and hypertension.
Increases in liver function tests (ALT and AST) were seen in some patients;
these increases were generally mild and reversible, with no hepatic
injuries or any observed impact on liver function.




About IL-6



IL-6 is a common protein found in all joints in the body and is a
natural substance that can raise inflammation. Everyone has IL-6 in their
body, but people with RA may have too much. If approved, ACTEMRA will be
the first and only medication to specifically target IL-6 in patients with
RA.



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, 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 1.3 million adults 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 2007 Roche was named
Top Company of the Year by Med Ad News, one of the Top 20 Employers
(Science) and ranked the No. 1 Company to Sell For (Selling Power). In
previous years, Roche has been named as a Top Company for Older Workers
(AARP) and one of the Best Companies to Work For in America (Fortune). For
additional information about the U.S. pharmaceuticals business, visit our
websites: rocheusa or rocheusa



All trademarks used or mentioned in this release are protected by law.


References



(1) ACR20, ACR50, ACR70 represent the percentage of reduction (20%, 50%,
70%) in certain RA symptoms and measures that number of tender and
swollen joints, pain, patient's and physician's global assessments and
certain laboratory markers.



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

Eprodisate (Fibrillextm) Data Presented At The Meeting Of The European League Against Rheumatism (Eular)

Results from Neurochem's (NASDAQ: NRMX; TSX: NRM) two-year Phase II/III clinical trial for eprodisate (Fibrillex™), its investigational product candidate for the treatment of Amyloid A (AA) amyloidosis, will be presented this week during the annual meeting of the European League Against Rheumatism (EULAR) by Bouke P.C. Hazenberg, MD, Division of Rheumatology, Department of Medicine, University Hospital, Groningen, the Netherlands, and an investigator for the Phase II/III clinical trial.



"The benefits of Fibrillex™ to patients during this clinical trial are clinically important especially in terms of preserving kidney function. In addition, its safety profile, comparable to placebo, is very encouraging," said Dr. Hazenberg. "With a potential treatment on the horizon and effective means of diagnosis available, there is a good chance that patients who demonstrate symptoms will be identified more easily."


Dr. Hazenberg, on behalf of the eprodisate (FibrillexTM) Study Group, received a clinical science award for the research on the efficacy and safety of eprodisate (FibrillexTM) in the treatment of patients with AA amyloidosis. The prestigious EULAR/Abbott Award is given to lead investigators of the 12 most highly rated abstracts out of the thousands that were submitted to the organization. Six of the abstracts are in the field of basic science research and an equal number, applicable to Dr. Hazenberg's case, involve research in clinical medicine. This award was presented during Wednesday evening's opening ceremony by EULAR President, Professor Tore K. Kvien, MD.


A poster also to be presented at EULAR by Dr. Hazenberg, assesses the diagnostic performance of quantifying AA protein in fat tissue of all the patients in the study and suggests that fat aspiration biopsy is a simple and reliable method for diagnosing amyloidosis with minimum risks for patients.


About AA amyloidosis


AA amyloidosis is a progressive and fatal condition that occurs in a proportion of patients with long standing chronic inflammatory disorders, chronic infections and inherited diseases such as Familial Mediterranean Fever. The kidney is the organ most frequently affected by AA amyloidosis, and progression to dialysis and end-stage renal disease is the most common cause of death in this disease. New approaches to treatment for AA amyloidosis are urgently needed due to lack of specific therapies.



About eprodisate (Fibrillex™)


Eprodisate (Fibrillex™) has been shown to reduce amyloid deposition in a mouse model of the disease. Results from a completed Phase II/III clinical trial with AA amyloidosis patients found eprodisate (FibrillexTM) to have a favorable clinical benefit on renal function/all-cause mortality. The product candidate was well tolerated and the adverse events profile of eprodisate (FibrillexTM) was comparable to placebo.



About regulatory submission status of eprodisate (FibrillexTM)















While there is no specific treatment approved for use, the new drug application for eprodisate (Fibrillex™) for the treatment of AA amyloidosis has been filed and received priority review by the US Food and Drug Administration (FDA) last April. The FDA is expected to render a decision on eprodisate (Fibrillex™) around mid-August 2006. Neurochem expects to submit a Marketing Authorization Application to the European Medicines Agency (EMEA) in the fall of 2006.



Neurochem has an exclusive collaboration and distribution agreement for eprodisate (FibrillexTM) with Centocor, Inc.



About Neurochem


Neurochem is focused on the development and commercialization of innovative therapeutics to address critical unmet medical needs. Eprodisate (Fibrillex™) is designated as an orphan drug, is a Fast Track product candidate and is also part of the US Food and Drug Administration (FDA) Continuous Marketing Application Pilot 1 and Pilot 2 programs. In April 2006, the FDA filed and granted the eprodisate (Fibrillex™) new drug application priority review. Tramiprosate (Alzhemed™), for the treatment of Alzheimer's disease, is currently in Phase III clinical trials in both North America and Europe and tramiprosate (Cerebril™), for the prevention of Hemorrhagic Stroke caused by Cerebral Amyloid Angiopathy, has completed a Phase IIa clinical trial.



neurochem.



This news release contains forward-looking statements regarding eprodisate (Fibrillex™), as well as regarding continuing and further development efforts. These statements are based on the current analysis and expectations of management. Drug development necessarily involves numerous risks and uncertainties, which could cause actual results to differ materially from this current analysis and these expectations. Analysis regarding the results of clinical trials may not provide definitive results regarding safety, tolerability or therapeutic benefits. Even if all the endpoints sought in the clinical trials were met (which is not certain), there is no certainty that regulators would ultimately approve eprodisate (Fibrillex™) for sale to the public. Risks and uncertainties may include: failure to demonstrate the safety, tolerability and efficacy of our product, the expense and uncertainty of obtaining regulatory approval, including from the FDA, and the possibility of having to conduct additional clinical trials. Further, even if regulatory approval is obtained, therapeutic products are generally subject to: stringent on-going governmental regulation, challenges in gaining market acceptance, and competition. Neurochem does not undertake any obligation to publicly update its forward-looking statements, whether as a result of new information, future events, or otherwise. Please see the Annual Information Form for further risk factors that might affect the Company and its business.

Aging Gracefully, With A Chronic Disease

For the better part of three decades, Sherrie Kossoudji has endeavored each day to manage the inflammation, chronic pain, tight joints and other types of physical strife caused by rheumatoid arthritis. Now 53, Kossoudji is trying to sort out what is a normal part of aging, and what is a facet of RA.


For the better part of three decades, Sherrie Kossoudji has endeavored each day to manage the inflammation, chronic pain, tight joints and other types of physical strife caused by rheumatoid arthritis.


"Rheumatoid arthritis affects my life in as many ways as you could possibly imagine, and pretty much at all times," says Kossoudji. "It is a disease that can be manipulated with medicine, but it doesn't ever really go away."


Now 53, Kossoudji is dealing with a new aspect of her chronic disease: sorting out what is a normal part of aging, and what is a facet of rheumatoid arthritis, or RA. If she has a sore leg, a pain in her elbow or a kink in her wrist, is it because of RA or is there another cause?


"I have fingers that don't work well, joints that don't work well. I have a wrist that doesn't flex and neuropathies in my legs," she says. "I think it's difficult when someone has a long-term disease to separate what happens as the body ages from what happens when you have a disease for a very long time."


RA is debilitating for some patients as they age, so it is especially important for people with RA to see a rheumatologist to determine the best course of treatment and to gain the best possible understanding of what is happening in one's body, says David A. Fox, M.D., division chief and professor of rheumatology at the University of Michigan Health System. Fox is Kossoudji's rheumatologist.


Whatever the age of the patient's RA onset whether it is at a young age, like Kossoudji at the time of her diagnosis, or later in life Fox emphasizes that RA is not a normal part of aging. It is a specific condition with symptoms that can't be cured, but can be managed.


"Arthritis should not be considered just a part of the aging process or a normal part of getting older," Fox says. "There are some elderly people who don't have arthritis, and many people who develop arthritis when they are younger."


Many patients are helped by some of the available treatments, including pain relievers and anti-inflammatory medications known as nonsteroidal anti-inflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs, such as methotrexate and tumor necrosis factor (TNF) blockers. Exercise, weight loss and diet changes also can be helpful, Fox says.


RA is one of more than 100 varieties of arthritis, a wide-ranging set of conditions that affects 70 million people in the United States. RA involves a malfunctioning of the immune system that causes inflammation in the lining of the joints. With time, the cartilage and bone are attacked and invaded, Fox says, to the point that the structure of the joint can be destroyed. This can lead to deformities and disabilities.















"Patients may develop inflammation in their lungs or peripheral nerves, inflammation in the salivary glands or tear glands that prevent them from functioning normally, and they may become what we call 'systemically ill' that is, the disease can affect the patient's body as a whole," he says.


One very important thing that Fox tells his patients with RA is that they do not have to stop living their lives. Kossoudji, for one, has followed the advice. "My job is to make sure that rheumatoid arthritis diminishes my life as little as possible," she says. "My goal is not to overcome the disease, but to do my best at managing the disease."


7 facts about rheumatoid arthritis


1. What it is: Rheumatoid arthritis (RA) is a disease that causes pain, stiffness, swelling and loss of motion in the joints. It occurs most commonly in the fingers, wrists, elbows, shoulders, jaw, hips, knees and toes. RA often appears first in early adulthood or middle age, but sometimes does not occur until the later years. (Osteoarthritis is another common type of arthritis; it causes a breakdown of the cartilage in the joints.)


2. Symptoms: Symptoms include joint pain and stiffness, particularly in the morning; red, warm or swollen joints; deformity of the joints; mild fever; fatigue; loss of appetite; anemia; and small lumps or nodules under the skin. Symptoms can be present nearly every day, or they can come and go.


3. Diagnosis: Your health care provider will review your medical history and examine you. He or she may order blood tests and x-rays to confirm the diagnosis and measure the extent of the disease.


4. Prevention: The best ways to try to prevent arthritis, Fox says, are maintaining a good body weight and not smoking. To try to prevent osteoarthritis, he also advises that you use common sense when engaging in strenuous physical activity so you don't seriously injure your joints.


5. Who is at risk: RA can affect people of different ages, races and sexes; it is three times more common in women than men. Genetics can affect a person's chance of developing RA, but if one of your parents had the condition, it does not necessarily mean that you will. Being overweight is a major risk factor for osteoarthritis, and recent studies have shown that smokers may have twice the chance of developing RA as non-smokers.


6. Treatment: RA can be managed but not cured. The goal of treatment is to keep the joints working properly by reducing inflammation, relieving the pain and stiffness, and stopping or slowing down joint damage. Many drugs are used for the long-term relief of rheumatoid arthritis. One type is nonsteroidal anti-inflammatory drugs (NSAIDs) that treat pain and inflammation (aspirin, ibuprofen and naproxen are NSAIDs that are available without a prescription, and others are available by prescription only). When NSAIDs do not work, disease-modifying antirheumatic drugs (DMARDs) may be used, with careful supervision by a rheumatologist. Methotrexate and tumor necrosis factor (TNF) blockers are examples of DMARD that have been found to be helpful for many RA patients. Injections, physical therapy and surgery are other potential treatments.


7. Possible treatment in the future: Ongoing research offers significant hope that in the future, cures will be available for RA, Fox says.


University of Michigan Health System

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Ann Arbor, MI 48109-2435

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NICE Recommends Golimumab For The Treatment Of Psoriatic Arthritis

The National Institute for Health and Clinical Excellence (NICE) has issued final draft guidance recommending golimumab (Simponi, Merck Sharpe & Dohme) for the treatment of psoriatic arthritis.


Additional information from the manufacturer, considered by the independent Appraisal Committee following a consultation on its earlier draft recommendation, suggests that golimumab may be added to the list of treatment options already recommended by NICE for this condition.


Specifically, golimumab is recommended as an option for the treatment of active and progressive psoriatic arthritis in adults if it is used as described for the other tumour necrosis factor (TNF) inhibitor treatments - etanercept, infliximab and adalimumab - covered by NICE technology appraisal 1991. The recommendation of golimumab for use within the NHS is also dependent on the patient access scheme agreed between the manufacturer and the Department of Health, whereby the manufacturer provides both of the available doses of golimumab (50 mg and 100 mg) to the NHS at the cost of the 50 mg dose.


Dr Carole Longson, Health Technology Evaluation Centre Director at NICE, said: "We already recommend three TNF inhibitor treatments for psoriatic arthritis that has not responded to first-line treatment. We're glad that extra information from the manufacturer has meant that our Appraisal Committee now feels confident in recommending golimumab as a fourth treatment option. We recognise that patients may welcome the option of a self-injectable treatment that only has to be administered once a month."


The final draft guidance is now with consultees, who have the opportunity to appeal against it. NICE has not yet issued final guidance to the NHS.


Notes


References


1. NICE technology appraisal 199 recommends adalimumab, etanercept and infliximab for the treatment of psoriatic arthritis when the person has peripheral arthritis with three or more swollen joints, and when the psoriatic arthritis has not responded to adequate trials of at least two standard DMARDs (administered either individually or in combination). NICE TA 199 specifies that treatment should be with the least expensive drug, taking into account drug administration costs, required dose and product price per dose.


About the appraisal


1. Golimumab (Simponi, Merck Sharpe & Dohme) is a human monoclonal antibody that prevents the binding of tumour necrosis factor (TNF) to its receptors, thereby neutralising its activity. Golimumab has a marketing authorisation for the treatment of active and progressive psoriatic arthritis (alone or in combination with methotrexate) in adults when the response to previous disease-modifying anti-rheumatic drug (DMARD) therapy has been inadequate.


2. Golimumab is injected subcutaneously via a pre-filled injection pen. The recommended dose is 50 mg given once a month, on the same date each month. The SPC states that in people who weigh more than 100 kg whose psoriatic arthritis does not show an adequate clinical response after three or four 50mg doses, the dose of golimumab may be increased to 100 mg once a month. The manufacturer's submission states that the cost of golimumab is ??774.58 for a 50mg pre-filled injection pen, and estimates an annual cost of ??9294.96. With the agreed patient access scheme, the cost of the 100mg dose is the same as the 50mg dose. This annual cost for golimumab is very similar to the annual costs for adalimumab and etanercept. The annual cost of infliximab varies depending on the weight of the patient. Costs may vary in different settings because of negotiated procurement discounts.


Source:

NICE


View drug information on Simponi.

In RA Patients, Expression Of Certain Transporter Proteins May Predict Resistance To Drug Therapy

The expression of a transporter protein called the Breast Cancer Resistance Protein (BCRP) in rheumatoid arthritis (RA) patients may indicate higher disease activity and could be a barrier to the effectiveness of disease-modifying antirheumatic drugs (DMARDs), according to the results of a study presented at EULAR 2010, the Annual Congress of the European League Against Rheumatism in Rome, Italy.



In a Turkish study, researchers analysed specimens of synovium (the soft tissue that lines the surfaces within joints) from patients with RA who had undergone knee or hip replacement surgery. The presence of BCRP was reported in 41% of samples from RA patients, compared with 0% of samples in the healthy control group. The level of BCRP staining (a technique where a stain specific to a particular protein is used) was more prominent, indicating that the protein was being expressed at higher levels in cells actively involved in the immune response (macrophages, endothelial cells and fibroblasts).



Furthermore, of the 40% of RA patients with cells that showed a presence of BCRP, some had a higher concurrent disease activity score (DAS28, an index that rates scores of 28 tender and swollen joints) despite receiving treatment for their condition, when compared with patients without BCRP. Researchers noted that this difference was not statistically significant (4.32?±0.32 vs 3.37?±1.16, p>0.05).



"The results of our study show that the presence of BRCP was only detected in patients with RA and that arguably it is found more prominently in patients with high disease activity," said Dr. Umut Kalyoncu, Hacettepe University Rheumatology Department, Ankara, Turkey, and lead author of the study. "The BCRP protein is a pump involved in transporting substances across the cellular membrane. What we hypothesise is that, due to the location of the cells showing highest levels of BCRP, the presence of this protein may create a barrier for treatments entering the synovium of RA patients. Testing RA patients for the presence of BCRP may help us determine which patients will respond better to certain treatments."



Researchers screened samples using histochemical methods from seventeen patients (female n=14) with RA for the presence of p-glycoprotein (a protein involved in the transport of various molecules across cellular membranes), BCRP and multidrug resistance protein 1 and compared with samples taken from a control group of healthy controls and other inflammatory (ankylosing spondylitis, juvenile chronic arthritis) and non-inflammatory (osteoarthritis) rheumatic diseases. Prior to surgery, 53% of patients were taking methotrexate, 47% were taking sulphasalazine, 70% hydroxychloroquine, 18% leflunomide and 12% were taking anti-TNF drugs.



Abstract Number: FRI0129



Source:

Rory Berrie


European League Against Rheumatism

ACTEMRA (R) (tocilizumab) Significantly Reduced Signs And Symptoms Of Rheumatoid Arthritis In Patients Who Failed Prior Treatments

Data from two Phase III studies
showed that patients who suffer from the debilitating and painful effects
of rheumatoid arthritis (RA) achieved significant improvements in signs and
symptoms when treated with ACTEMRA(R) (tocilizumab) alone or in combination
with methotrexate compared with methotrexate alone. The final results of
both studies will be presented as oral presentations, along with 13 other
abstracts which evaluate ACTEMRA in patients with moderately to severely
active RA, at the American College of Rheumatology (ACR) Annual Scientific
Meeting in San Francisco, October 24-29.



Results of the RADIATE study, which evaluated difficult-to-treat
patients who failed to respond to prior anti-tumor necrosis factor
(TNF)-alpha therapies, demonstrated that half of patients treated with
ACTEMRA (8 mg/kg) in combination with methotrexate achieved a 20 percent
reduction (ACR20)(1) in RA signs and symptoms, compared with 10 percent of
patients treated with methotrexate alone.



"Despite treatment with existing therapies, many patients with RA
continue to experience symptoms of joint pain and stiffness," said Mark
Genovese, M.D., Professor of Medicine at Stanford University School of
Medicine. "The compelling results of these studies further support the
efficacy and safety of ACTEMRA as a potential new treatment option for
managing the chronic signs and symptoms of this debilitating disease."



The AMBITION study, which examined the effects of ACTEMRA (8 mg/kg) as
monotherapy, showed that 70 percent of patients receiving ACTEMRA achieved
a 20 percent improvement in their signs and symptoms (ACR20), compared with
53 percent of patients receiving methotrexate alone. The study not only
successfully met its primary endpoint of non-inferiority in patients with
moderate to severe RA, but also demonstrated superiority over the standard
effective dose regimen of methotrexate alone.



In both studies, nearly one-third of all ACTEMRA (8 mg/kg) patients
achieved disease remission (as defined by DAS28








Treatment with ACTEMRA and methotrexate showed significant clinical
benefits even in the subgroup analysis of difficult-to-treat patients who
received up to three anti-TNF-alpha therapies that failed.



The most common adverse reactions reported most frequently in the
ACTEMRA arms of the RADIATE study were diarrhea, upper abdominal pain, rash
and dizziness.



About the AMBITION Study



AMBITION (Actemra versus Methotrexate double-Blind Investigative Trial
In mONotherapy), a two-arm, randomized, double-blind, placebo-controlled
study, was designed to evaluate the non-inferiority and subsequent
superiority of ACTEMRA monotherapy in patients with RA compared with
methotrexate alone at 24 weeks. Patients who had not received methotrexate
for at least six months beforehand were randomized to receive either
ACTEMRA (8 mg/kg) intravenously every four weeks plus placebo capsules
weekly or placebo infusions every four weeks plus methotrexate weekly. The
study evaluated 673 patients from 252 sites in 18 countries, including the
United States.



In the AMBITION study, 70 percent, 44 percent and 28 percent of
patients in the ACTEMRA (8 mg/kg) arm achieved ACR20, ACR50 and ACR70,
respectively, compared with 53 percent, 34 percent and 15 percent,
respectively, of patients treated with methotrexate alone. Disease
remission (DAS28

Nearly Half Of US Adults Will Develop Painful Knee Osteoarthritis By Age 85: Study

Almost half of all U.S. adults and nearly two-thirds of obese adults will develop painful osteoarthritis of the knee by age 85, a study based at the University of North Carolina at Chapel Hill suggests.



The study also found that a person's lifetime risk rose as their body mass index or BMI increased, with the greatest risk found in those whose weight was normal at age 18 but were overweight or obese at 45 or older.



"These results show how important weight management is for people throughout their lives," said Dr. Joanne Jordan, principal investigator of the Johnston County Osteoarthritis Project and senior study author. "Simply put, people who keep their weight within the normal range are much less likely to develop symptomatic knee osteoarthritis as they get older and thus much less likely to face the need for major surgical procedures, such as knee replacement surgery."



The study also sends an important message to physicians, said Jordan, director of the Thurston Arthritis Research Center and professor of medicine and orthopaedics in the School of Medicine at the University. "They need to include the risk of knee osteoarthritis in the discussion when counseling patients about weight management and they need to factor that risk into their treatment plans."



The results were published in the Sept. 15, 2008 issue of Arthritis Care & Research. Lead author of the report is Louise Murphy, Ph.D. of the Centers for Disease Control and Prevention in Atlanta. Murphy led the data analysis and the CDC is the primary funder of the Johnston County Osteoarthritis Project.



In the study, researchers collected and analyzed data over a 13-year period from 3,068 men and women 45 years old and older who live in Johnston County, N.C. At two separate points during the study, each participant was interviewed at home and given a clinical exam that included taking X-ray images of their knees and measuring their BMI. They were interviewed a second time two weeks after the clinical exam. In addition, researchers calculated the subjects' BMI at age 18 based on their self report of height and weight at that age.



After all data were collected, researchers estimated the lifetime risk of symptomatic osteoarthritis in at least one knee using logistic regression models of statistical analysis. They found that the lifetime risk of symptomatic knee osteoarthritis was 44.7 percent.



There were no significant differences in risk related to a participant's sex, race or education level. However, obese participants had a significantly higher lifetime risk, 64.5 percent compared to 34.9 percent for normal weight and 44.1 percent for overweight participants. Those with a history knee injury also had a higher risk than those without, 56.8 percent compared to 42.3 percent.



A separate analysis of BMI across the span of participants' lives found that those who had a normal weight at age 18 and at their baseline and follow up visits had the lowest risk (29.2 percent) while those who reported a normal weight at 18 but were overweight or obese at the two later time points had the highest risk (59.9) percent.



Although the participants in this study all live in the same relatively rural county in the South, the lifetime risk of knee arthritis is likely high in the rest of the U.S. as well, the researchers wrote. They concluded that the study "underscores the need for public health weight loss and management interventions" that would help decrease the risk.



Notes:



Besides Jordan, UNC authors of the study include Todd A. Schwartz, Dr.P.H., Gary Koch, Ph.D. and William D. Kalsbeek, Ph.D., all from the UNC School of Public Health; and Jordan B. Renner, M.D., from the School of Medicine.



In addition to Murphy, study authors not at UNC include Charles G. Helmick, M.D., of the CDC; Gail Tudor, Ph.D. of Huston College in Bangor, Maine; Anca Dragomir, Ph.D., who earned her Ph.D. at UNC but now works at the National Institutes of Health; and Gheorghe Luta, Ph.D., who also earned his Ph.D. at UNC and is now at Georgetown University Medical Center.



Source:

Stephanie Crayton

University of North Carolina School of Medicine