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10/26/2001

Heart Disease, Infection Concerns Prompt Infliximab Warnings

Kate Traynor

Centocor Inc. recently warned health care providers that the company’s infliximab product, Remicade, may be deadly for patients with moderate to severe congestive heart failure (CHF).

In a "Dear Healthcare Professional" letter dated Oct. 18, Centocor said a preliminary analysis of data from a Phase II study involving patients with moderate to severe CHF revealed that seven of the 101 patients taking infliximab had died. None of the 49 patients assigned to a placebo group had died by the time of the analysis. Infliximab use also apparently increased the patients’ likelihood of hospitalization for worsening heart failure. The risk of death or hospitalization seemed to be dose related, with patients who received three 10-mg/kg doses of infliximab faring worse than those given three 5-mg/kg doses.

Infliximab, a monoclonal antibody that binds to tumor necrosis factor-alpha, is indicated for treatment of rheumatoid arthritis or Crohn’s disease. On the basis of the new data, Centocor asked health care providers not to initiate infliximab therapy in patients with CHF. Clinicians should tell patients with CHF who have already begun infliximab therapy to stop taking the drug if their cardiac symptoms worsen.

For users who have stable CHF, clinicians should consider stopping infliximab therapy, especially if the drug has not improved the symptoms of rheumatoid arthritis or Crohn’s disease, Centocor advised. Patients who continue to take infliximab should be "closely monitored" for worsening cardiac symptoms.

Centocor said the company will continue to monitor the progress of the patients who had participated in the Phase II study and will update clinicians and the Food and Drug Administration on any important, new clinical findings. An Oct. 22 press release from Centocor said the patients in the study derived no clinical benefit from infliximab therapy and the company has cancelled its plans to test the drug in additional patients with CHF.

About two weeks before releasing the warning about use of its product by patients with CHF, Centocor announced that it had added to Remicade’s labeling a "black box" advising clinicians that infliximab use increases patients’ risk of tuberculosis, invasive fungal infections, and other opportunistic infections.

Between Aug. 24, 1998, and June 30, 2001, 84 cases of tuberculosis were reported in infliximab users in the United States and elsewhere, according to Centocor. The company reported that 14 of these patients had died, although not all deaths were attributed to tuberculosis.

The black-box warning advises physicians to test patients for latent tuberculosis infection and treat the disease, if discovered, before starting infliximab therapy. An additional warning in the package insert advises physicians to carefully consider the risks and benefits of infliximab treatment before prescribing the drug to a patient who has lived in an area where histoplasmosis, a fungal disease, is endemic.