Remicade May Be Associated With Increased Risk of Lymphoma

Yael Waknine


October 14, 2004

Oct. 14, 2004 — The U.S. Food and Drug Administration (FDA) and Centocor have warned healthcare professionals via letter of an increased risk of lymphoma associated with the use of infliximab (Remicade) in patients with rheumatoid arthritis (RA) and Crohn's disease, according to an alert sent yesterday from MedWatch, the FDA's safety information and adverse event reporting program.

The warning applies to all therapeutic agents that block tumor necrosis factor α (TNFα) and is based on a review of safety data from controlled clinical trials and postmarketing reports by the FDA's Arthritis Advisory Committee.

In the controlled portions of clinical trials of all TNFα-blocking agents, lymphoma occurred with greater frequency in the therapeutic group compared with the control group. In controlled portions of infliximab trials in patients with moderately to severely active RA and Crohn's disease, one of 1,389 patients treated with infliximab developed lymphoma during a median follow-up period of 1.1 years compared with none of 483 control patients.

Of 2,410 patients treated with infliximab in the controlled and open-label portions of these trials, three patients developed lymphomas. The incidence of lymphoma associated with infliximab use in patients with RA (0.07 cases/100 patient-years of follow-up) and Crohn's disease (0.12 cases/100 patient-years of follow-up) was 3-fold and 6-fold, respectively, more than expected in an age-, sex-, and race-matched general population based on the Surveillance, Epidemiology, and End Results Database.

The FDA notes that incidence rates of lymphoma observed in infliximab trials cannot be compared to rates demonstrated in clinical trials of other TNFα blockers and may not predict those of a broader patient population. Patients with RA and Crohn's disease, particularly those with highly active disease and/or chronic exposure to chronic immunosuppressant therapies may be at a higher risk (up to several fold) than the general population for the development of lymphoma.

The FDA has also received postmarketing reports of malignancies, including non-Hodgkin's lymphoma and Hodgkin's disease, in patients receiving infliximab therapy. Clinical trials showed development of malignancies other than lymphoma (breast, colorectal, and melanoma) in 13 patients, at an incidence rate similar to that of the general population.

According to the FDA, the potential role of TNFα-blocking therapy in the development of malignancies is unknown. Because no studies have included patients with a history of malignancy or continued infliximab therapy in patients developing malignancies, the FDA advises caution in considering infliximab therapy in these patients.

Additional information regarding the use of infliximab may be obtained by calling Centocor's Medical Affairs Department at 1-800-457-6399.

Adverse events related to the use of infliximab can be reported to Centocor at 1-800-457-6399. Alternatively, this information can be reported to the FDA's MedWatch program by phone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at, or by mailing Form 3500 to 5600 Fishers Lane, Rockville, MD 20852-9787.

Reviewed by Gary D. Vogin, MD


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