FDA Panel Scrutinizes Safety Of 4 Rheumatoid Arthritis Drugs

The risk versus benefit of Arava, Enbrel, Remicade, and Humira is reconsidered.

FDA approved stamp
FDA panel on arthritis drugs. Daniel Hurst Photography / Getty Images

This article is part of the Arthritis Archives.

Dateline: March 7, 2003

FDA Panel Scrutinizes Safety

The Arthritis Advisory Committee met on March 4-5, 2003 to reconsider the safety of 4 popular drugs used in the treatment of rheumatoid arthritis.

The advisory committee which makes recommendations to the FDA, debated over:

  • the association of liver failure with use of Arava (leflunomide)
  • the association of lymphoma with anti-TNF drugs Enbrel (etanercept), Remicade (infliximab), and Humira (adalimumab)


    Arava (generic name leflunomide), which was first marketed in 1998 for the treatment of rheumatoid arthritis, works similarly to methotrexate which is considered the standard treatment for rheumatoid arthritis.

    A consumer advocacy group, Public Citizen, has implored the FDA to revisit the safety issue of Arava, citing 54 cases of liver failure in the United States and eight deaths linked to the drug. Public Citizen petitioned the FDA to ban Arava in March 2002. Some FDA officials agreed with the position taken by Public Citizen and issued a memo accordingly in November 2002.

    However, the Arthritis Advisory Committee concluded differently by a unanimous vote (12-0) on March 5, 2003, stating that the benefits of Arava outweigh its risks. The Arthritis Advisory Committee also voted that effectiveness data supports Aventis' latest claim that Arava improves physical function in rheumatoid arthritis patients, in addition to its current indication for relieving the signs and symptoms of rheumatoid arthritis and retarding structural damage.

    Aventis is the maker of Arava.

    TNF Blocker Drugs

    The FDA also is trying to establish whether there is a link between the use of Enbrel (etanercept), Remicade (infliximab), and Humira (adalimumab) and 170 cases of lymphoma reported since 1998.

    The Arthritis Advisory Committee has concluded that more data is needed to determine if there is causality between the use of the anti-TNF drugs and lymphoma.

    Recommending that the potential problem should be monitored and recognizing that it is a process which may take years before a final conclusion is reached, the advisory committee noted that the drugs label should reflect a warning. The drug manufacturers maintain that the patients have already received sufficient warning. Amgen manufactures Enbrel, while Johnson & Johnson manufactures Remicade. Humira, the newest of the anti-TNF drugs, is made by Abbott Laboratories.

    Since rheumatoid arthritis patients get lymphoma at a two to three times higher rate than the general population because the disease itself increases the risk, it is difficult to determine the role played by the drugs. Only 29 of the 170 reported cases of lymphoma occurred during a formal study which could be fully analyzed. While all three makers of the anti-TNF drugs continue to study the issue, they maintain that the drugs benefits outweigh the risks.

    It is clear that for the 2 million people who suffer with rheumatoid arthritis, various treatment options are needed, since not all drugs work equally for all patients. The aforementioned four drugs have benefited thousands of rheumatoid arthritis sufferers tremendously.

    Still, the safety profile of each drug must allow the patient a comfort zone when weighing pros and cons, benefits and risks.

    Related Resources


    Gov't Debates Risks of Arthritis Drugs, AP, 3/5/03; Arthritis Drug Risks Acceptable - U.S. Panel, Reuters, 3/6/03; FDA Panel Wants More Data On Arthritis Drug Risk, 3/5/03; Arthritis Drug Should Be Removed From Market, Public Citizen, March 28, 2002
    First published: 3/7/2003

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