Background: Chronic granulomatous disease is an uncommon inherited disorder of phagocytes in which defective production of the reactive intermediates of oxygen predisposes patients to recurrent and severe pyogenic infections. Evidence from in vitro and in vivo studies indicates that interferon gamma can partially correct the metabolic defect in phagocytes. We assessed the efficacy of interferon gamma in decreasing the frequency of serious infections in patients with this disease.
Methods: We conducted a randomized, double-blind, placebo-controlled study in 128 patients with chronic granulomatous disease (median age, 15 years). Patients received interferon gamma (50 micrograms per square meter of body-surface area) or placebo subcutaneously, three times a week for up to a year. The primary end point of the study was the time to the first serious infection, defined as an event requiring hospitalization and parenteral antibiotics. Measures of phagocyte function were also monitored.
Results: In terms of the time to the first serious infection, there was a clear benefit from interferon as compared with placebo (P = 0.0006). Of the 63 patients assigned to interferon, 14 had serious infections, as compared with 30 of the 65 patients assigned to placebo (P = 0.002). There was also a reduction in the total number of serious infections--20 with interferon as compared with 56 with placebo (P less than 0.0001). Interferon was beneficial regardless of age, the use or nonuse of prophylactic antibiotics, and the mode of inheritance (X-linked or autosomal recessive). However, there were no significant changes in the measures of superoxide production by phagocytes. Interferon therapy was well tolerated, and there was no evidence of serious toxicity.
Conclusions: For patients with chronic granulomatous disease, interferon gamma therapy is an effective and well-tolerated treatment that reduces the frequency of serious infections.