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Arava in Combination with Methotrexate More Than Doubles - Patient Response in Rheumatoid Arthritis Compared to Treatment with Methotrexate Alone

PHILADELPHIA, Oct. 30, 2000 - Rheumatoid arthritis sufferers treated with a combination of the medicines Arava (leflunomide) and methotrexate were more than twice as likely to experience significant symptomatic improvement when compared to those sufferers receiving methotrexate alone, according to data presented today at the 64th Annual American College of Rheumatology (ACR) Meeting. In addition, a separate analysis of the same study showed that patients receiving the combination of Arava and methotrexate experienced significantly greater improvements in health-related quality of life and physical function compared to those patients treated with methotrexate alone.

"Patients unresponsive to methotrexate alone had demonstrated enhanced benefits with the addition of Arava, and the combination proved to be well tolerated" said Joel M. Kremer, current director of research at the Center for Rheumatology in Albany, New York and former head of the Division of Rheumatology at Albany Medical College. "The data provide further evidence for physicians to re-evaluate their standard treatment protocol for RA."

Addition of Arava to Methotrexate Effective in Patients Failing on Methotrexate Alone The study presented today was a 24-week multicenter, randomized, placebo-controlled trial that evaluated 263 patients with active RA and were failing treatment with methotrexate alone. A total of 130 patients were randomized to receive 10 mg/day of Arava together with methotrexate (mean dose = 16.7 mg/wk), while 133 patients were assigned to a group receiving placebo with methotrexate (mean dose = 16.2 mg/week). Dose adjustments were made based on tolerability and efficacy.

Response rate when Arava was added to methotrexate was 51.5 percent and this was significant compared to 23.3 percent when placebo was added. The even more stringent Responder at Endpoint rate showed significant improvement of 46.2 percent for the Arava and methotrexate group versus 19.5 percent for the placebo plus methotrexate group. Efficacy was measured by ACR 20 response rates assessed at 24 weeks using the last observation carried forward method (LOCF) including all patients who entered the trial. ACR criteria for response include the following: 1) at least a 20 percent improvement in both tender and swollen joint count, and 2) at least a 20 percent improvement in three of the following five criteria: patient's assessment of disease activity; investigator's assessment of disease activity; pain intensity; functional/disability measure; and acute phase reactants. 

Arava Improves Health-Related Quality of Life and Physical Function
A separate analysis of the study examined the effects of the Arava and methotrexate combination on health-related quality of life and physical function. Improvement was assessed at 24 weeks through questionnaires designed to measure the ability to conduct daily activities.

These validated questionnaires included the Health Assessment Questionnaire Disability Index 1 (HAQ) which assesses physical disability, and the Short-Form Medical Outcomes Survey 2 (SF-36), which measures physical function, well-being and overall evaluation of health.

The Disability Index found patients receiving Arava and methotrexate therapy reported a 29 percent improvement in performing their daily activities, compared to a 5 percent improvement reported by patients receiving methotrexate alone. Additionally, the Physical Component score assessing physical function derived from the SF-36, demonstrated a 29 percent improvement among the patients receiving Arava and methotrexate, while patients on methotrexate alone showed a 3 percent improvement. Overall, improvements in health-related quality of life and physical function among patients receiving Arava and methotrexate were significantly better than those patients receiving methotrexate alone.

"Patients receiving Arava in addition to methotrexate reported greatly improved quality of life and physical function in daily living compared to those patients receiving just methotrexate," said Daniel E. Furst, director of the Arthritis Clinic at the Virginia Mason Research Center in Seattle. "This study is important as these outcomes reflect significant aspects of RA patients' lives." 

Arava, a new DMARD, has been approved for marketing in Europe and the U.S. for the treatment of active rheumatoid arthritis in adults to improve the signs and symptoms of RA. Arava was launched throughout Europe and most of Central and South America in 1999. In the U.S., Arava is indicated to retard structural damage as evidenced by X-ray erosions and joint space narrowing and has been available to patients in the U.S. since September 1998. Most recently, Arava received approval in Canada and Australia.

In previous monotherapy trials, Arava was generally well tolerated with overall tolerability comparable to sulfasalazine and methotrexate. The most commonly reported side effects associated with treatment with Arava were transient and included diarrhea, elevated liver enzymes (ALT and AST), reversible alopecia (hair loss), rash and nausea. In the study reported today, the combination of Arava with methotrexate was also well tolerated with the most commonly reported adverse events consisting of diarrhea, nausea, dizziness, and elevated liver enzymes.

Rheumatoid Arthritis: A Crippling Autoimmune Disease
Rheumatoid arthritis, one of the most common forms of arthritis, affected approximately 6.2 million people in developed countries in 1999. It is a chronic and debilitating autoimmune disease in which the body's immune system attacks healthy tissue lining the joints, leading to pain, deformity and disability. This disease greatly impacts the sufferer's functional ability and quality of life. RA can limit a person's ability to carry out normal daily activities, including cooking, getting dressed or driving a car. RA can affect anyone, including children and the elderly, although it usually begins in middle age. The disease is approximately three times more common in women than in men.

Aventis Pharma AG is the pharmaceutical company of Aventis S.A. Aventis Pharma is dedicated to treating and preventing human disease through the discovery, development, manufacture and sale of innovative pharmaceutical products aimed at satisfying unmet medical needs. Aventis Pharma focuses on important therapeutic areas such as cardiology, oncology, infectious diseases, arthritis, allergies and respiratory disorders, diabetes and the central nervous system disorders. Aventis Pharma has its corporate headquarters in Frankfurt, Germany. Aventis Pharma encompasses Aventis Pasteur, a world leader in vaccines based in Lyon, France, and Aventis Behring, a world leader in therapeutic proteins headquartered in King of Prussia, Pennsylvania, USA.

1. Health Assessment Questionnaire (HAQ) evaluates difficulty in performing daily physical activities including: dressing and grooming, rising, eating, walking, hygiene, reach, grip and self-maintenance. HAQ is a globally recognized measurement standard.

2. The Short Form Medical Outcomes Survey (SF-36) includes one multi-item scale that assesses eight health concepts: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions.

Some of the information contained herein may cite the use of Arava in a dosage, for an indication, or in a manner other than recommended. Before prescribing the product, please consult the local affiliate and/or the locally approved prescribing information.

Jo Moseley
Cohn & Wolfe Healthcare
Tel. +1 (347) 645 4793

Doug Stokke
Aventis Pharma
Tel. +1 (908) 231 4659

Jennifer Gottlieb
Cohn & Wolfe Healthcare
Tel. +1 (917) 816 1660 


Posted: June 2004