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New Data Indicate Arava Significantly Improves LongTerm Functional Ability in Rheumatoid Arthritis

FRANKFURT, Germany, June 22, 2000 - Aventis Pharma's oral rheumatoid arthritis (RA) medication, Arava (leflunomide) is superior to methotrexate at two years in improving physical function and health related quality of life in rheumatoid arthritis patients, according to data presented this week by Dr. Vibeke Strand at the 15th European League Against Rheumatism Congress (EULAR) in Nice, France. Additional data presented by Dr. D.L. Scott indicated that Arava improved function compared with methotrexate and sulfasalazine as early as four weeks.

"RA is a debilitating disease that can have devastating effects on patients' ability to perform daily activities. In this two year study, Arava demonstrated superior efficacy versus methotrexate at all endpoints measuring patient function, including health related quality of life," said Dr.Vibeke Strand, Clinical Associate Professor at Stanford University, Stanford, CA. "This trial suggests that Arava is an effective agent for long-term prevention of disability in patients with RA, helping them gain independence from the disease."

Included in the EULAR presentations were two-year data from US trials comparing Arava to methotrexate and one-year multinational pooled data comparing Arava to methotrexate and sulfasalazine.

Arava Demonstrates Significantly Greater Physical Function Compared to Methotrexate at Two Years

In this trial, improvement in physical function and health related quality of life with Arava was consistently maintained over two years and was statistically superior compared with methotrexate according to the HAQ Disability Index1 (-0.60 for Arava as compared to -0.37 for methotrexate) and Problem Elicitation Technique2 (-9.1 for Arava as compared to -4.3 for methotrexate). Improvement was assessed using these questionnaires designed to measure physical function in terms of their ability to conduct daily activities (e.g., walking, eating, dressing, washing) and their function in daily life.

In the one-year, phase III, placebo-controlled trial, 482 patients were given one of three treatments: Arava 20 mg/day after a loading dose of 100 mg/day for three days, placebo or methotrexate 7.5 mg/week with an increase to 20 mg/week for continued active disease. In a second-year continuation of the trial to ascertain maintained benefit over two years of treatment, methotrexate dose could be increased as high as 20 mg/week. Two hundred and thirty-five patients continued for a second year of therapy (Arava was compared to methotrexate only because of the predictably small number of patients continuing on placebo).

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.

Problem Elicitation Technique (PET) is a globally recognized measurement that asks patients to identify functional activities that are most affected by their RA and that they would most like to see improved by treatment. Patients rank the difficulty, severity, and/or frequency of performing these activities on a seven point scale. The top five scores of PET are determined by tabulating the five most important problems identified by patients.
Arava Demonstrates Significant Improvement of Patient Function as Early as Four Weeks Over Methotrexate and Sulfasalazine

Analysis of the one-year pooled data, Arava demonstrated the greatest improvement in Health Assessment Questionnaire scores at four weeks than the active comparators. Arava-treated patients reported greater improvement in physical function (HAQ) at four weeks (-0.21 for Arava as compared to -0.11 for methotrexate, -0.09 for sulfasalzine and -0.04 for placebo) due to its rapid onset of action. HAQ scores are sensitive measures of effective DMARD (disease-modifying anti-rheumatic drug) therapy especially early in the treatment process.

Data from three randomized double-blind RA trials were analyzed for changes in mean HAQ scores. In the analysis, 1,732 rheumatoid arthritis patients received one of four treatments: Arava 20 mg/d, sulfasalazine 2 g/d. methotrexate 15-20 mg/wk and placebo.

"We analyzed data of more than 1,700 patients from the Arava database. Arava was found to be the most effective DMARD therapy improving physical function after four weeks compared with methotrexate and sulfasalazine," said Dr. D.L. Scott of King's College Hospital, London, UK. "Further analysis showed that pain reduction was a dominant factor in the rapid improvement of function seen with Arava treatment."

Arava was generally well tolerated with overall tolerability comparable to sulfasalazine and methotrexate in the studies presented. Most common side effects associated with Arava were transient and included diarrhea, elevated liver enzymes (ALT and AST), reversible alopecia (hair loss), rash and nausea.

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.

Aventis Pharmaceuticals intends to file with the United States Food and Drug Administration for an indication expansion for Arava to include prevention of disability as evidenced by improved physical function.

Rheumatoid Arthritis: A Crippling Autoimmune Disease

Rheumatoid arthritis (RA), 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.

 Dr. Felicitas Feick
External Communications
Tel: +49 (69) 305 4995
Fax: +49 (69) 305 83852

Joachim Pietzsch
Scientific Public Relations
Tel.: +49 (69) 305 2987
Fax: +49 (69) 305 83852


Posted: June 2004