While the class of drugs known as tumor necrosis factor (TNF) blockers are probably the most important advance in the treatment of rheumatoid disorders in the past 20 or 30 years, experts have long debated the risk-benefit profile of the drugs. Now the Federal Drug Administration (FDA) has begun a safety review of the drugs which are prescribed to treat autoimmune disorders such as rheumatoid arthritis, juvenile rheumatoid arthritis, and Crohn's disease.

Among the chief concerns is whether the drugs are associated with the development of cancer, especially lymphoma, in children and young adults. The FDA is investigating 30 reports of cancer in this younger age group submitted since 1989, when the first TNF blocker was approved, through April 2008.

Four TNF blockers are currently approved in the United States: Enbrel (etanercept), Humira (adalimumab), Remicade (infliximab), and Cimzia (certolizumab). Enbrel and Humira are approved to treat children with juvenile rheumatoid arthritis, and Remicade is approved for use in children with Crohn's disease. The FDA is focusing on the first three although all four are approved for multiple indications.

Dr. Chaim Putterman, chief of the division of rheumatology at Montefiore Medical Center and Albert Einstein College of Medicine, New York City, points out that everyone would prefer an indication in children. He says, "It has always been a concern, and it's something that should be clarified.

Dr. Stephen Lindsey, head of rheumatology at Ochsner Health Service, in Baton Rouge, Louisiana, observes that TNF inhibitors "are being used earlier and earlier because they are so good." He adds, "I think the FDA is being cautious. I think it's smart. What are the risks of a child being crippled and non-functioning versus the risk of cancer? Maybe, in odd cases, we need to think more and not jump in with all four limbs."

Dr. Putterman comments, "The increased signal [for cancer] has not been a dramatic one. There are confounding factors in rheumatoid arthritis patients, which can make interpretation of the data more difficult." He says, "TNF plays an important role in immune surveillance and, by blocking it, you might be interfering with the body's own defenses."

Meanwhile, the FDA has advised healthcare professionals to weigh the possible risks against the benefits when prescribing TNF blockers.

Source: Adapted from "FDA Starts Safety Review of Autoimmune Disorder Drugs, Amanda Gardner, HealthDay Reporter, U.S.News & World Report, June 4, 2008