How Is Infliximab Harmful?

IN RESPONSE:

Although we appreciate Dr. Arkfeld's thoughtful communication, we stand by the original conclusion that the use of infliximab plus corticosteroids is of no benefit in the treatment of patients with newly diagnosed GCA and may be harmful. Clinical trials generally are too small for safety signals to be evaluated by using statistical testing. This is especially true for a trial the size of ours, and therefore a judgment regarding the benefit versus the risk must be based on clinical information. In our trial, 10 infusion reactions occurred in 6 patients in the infliximab group, whereas none occurred in the placebo group. Although most reactions were of only mild-to-moderate intensity, 1 patient discontinued therapy because of dyspnea and flushing. Although not of clinical consequence, antibodies to double-stranded DNA occurred in 16% of patients in the infliximab group and were not found in any patients in the control group.

Although not noted in our study, infliximab and other anti–tumor necrosis factor agents are known to have been infrequently, albeit significantly, associated with opportunistic infections, reactivation of tuberculosis, hepatitis B, and either reactivation or occurrence of fungal infections. Rare cases of hepatosplenic T-cell lymphoma have been reported in adolescent and young adult patients with Crohn disease treated with infliximab. Autoimmune events, including the appearance of antinuclear antibodies and antibodies to double-stranded DNA, lupus-like syndromes, immune-mediated hemocytopenia, optic neuritis, demyelinating disorders, and heart failure, may occur or be exacerbated by such therapy. Because of the unknown potential for and theoretical concerns over a role of anti–tumor necrosis factor therapy in increasing the risk for malignant conditions, its use is not advised in patients with a recent history of cancer, other than surgically cured skin cancer. Although our study did not show any new or unusual adverse events in the elderly patients studied, all the previously mentioned adverse events can occur in this patient population. With these issues in mind, as well as the absence of a signal to demonstrate efficacy for infliximab in new-onset GCA and the skewed occurrence of infusion reactions among patients who received experimental therapy, we felt it prudent to stop infusions after the interim analysis. Thus, possible future harm and a low likelihood of benefit with continued use of infliximab supported our decision and conclusions. This study does not address the issue of anti–tumor necrosis factor therapy in refractory GCA.