Updated June 09, 2015.

This article is part of the Arthritis Archives.

Editor note: On September 11, 1998, Arava was FDA approved for the treatment of active rheumatoid arthritis in adults.

Dateline: August 12, 1998

Arava Unanimously Recommended

The FDA (United States Food and Drug Administration) arthritis advisory committee has unanimously recommended that Arava, generic name leflunomide, be approved for the treatment of active rheumatoid arthritis.

Arava (leflunomide) is a product of Hoechst Marion Roussel. The impending approval of Arava would make it the first new DMARD (disease-modifying anti-rheumatic drug) specifically developed for the treatment of rheumatoid arthritis in more than ten years. The specific recommendation from the committee was that Arava be approved for relief of signs and symptoms and for the retardation of structural damage in rheumatoid arthritis. The committee also recommended that the FDA consider an inclusion of language regarding "improvement in physical function" on the label.

Arava Trials

The recommendations were based on results of placebo-controlled Phase III clinical trials. Hoechst studied 480 Americans with moderate rheumatoid arthritis.

• About 41 percent of patients taking Arava experienced improvement in their arthritic condition compared with 19 percent taking placebo.
• Patients receiving methotrexate improved about as much as patients receiving Arava in the trials.

Hoechst took x-rays of the hands and feet of the patients to track progression of the disease and to study bone erosion and cartilage loss.

It was revealed that patients on Arava did worsen, however, patients on placebo worsened four times more quickly. Methotrexate slowed the progression of the disease but not as much as Arava.

Arava Side Effects

Arava caused side effects in more than one-fourth of the patients but was considered generally well-tolerated. Arava side effects were generally reversible and not severe. The noted side effects included:

• diarrhea
• hair loss
• rash
• elevated liver function tests

Arava did not seem to cause the serious problems that methotrexate sometimes can cause, such as kidney failure. Both Arava and methotrexate work by blocking the overproduction of immune cells responsible for the inflammation of rheumatoid arthritis, but the drugs target different enzymes as they work. Arava works by reversibly inhibiting the enzyme DHODH which is part of the autoimmune process contributing to the disease.

Since Arava can take at least six months to clear out of the body and since animal studies suggested it can cause birth defects, FDA advisers warned that pregnant women should never take the drug. Premenopausal women should use birth control if using Arava.

Priority Review Status

Arava is much needed in the management of rheumatoid arthritis since existing drug therapies lose effectiveness over time. Arava has exhibited safe and effective use in both early and advanced rheumatoid arthritis. The committee's recommendation will be considered by the FDA in its final review of the New Drug Application submitted by Hoechst in March 1998. Arava had been placed on six-month priority review status by the FDA.

Related Resources

Arava (leflunomide)

Methotrexate

DMARDs (disease-modifying anti-rheumatic drugs)

Rheumatoid Arthritis

_{Sources: FDA Panel Recommends Arava For Adult Rheumatoid Arthritis, P/S/L Group, 8/10/1998: Advisers OK New Arthritis Drug, AP Online, 8/7/1998
First published: 8/12/1998}