Long-Term Interferon-γ Therapy for Patients with Chronic Granulomatous Disease

• Published in: Clinical infectious diseases 2004-09, Vol.39 (5), p.692-699
• Main Authors: Marciano, Beatriz E., Wesley, Robert, De Carlo, Ellen S., Anderson, Victoria L., Barnhart, Lisa A., Darnell, Dirk, Malech, Harry L., Gallin, John I., Holland, Steven M.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Antibacterial agents; Antibiotics; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal agents; Bacterial pneumonia; Biological and medical sciences; Child; Child, Preschool; Chronic granulomatous disease; Cytokines; Drug Administration Schedule; Female; Fever; Follow-Up Studies; Fungal infections; Granulomatous Disease, Chronic - complications; Granulomatous Disease, Chronic - drug therapy; Granulomatous Disease, Chronic - mortality; Hematologic and hematopoietic diseases; Humans; Infant; Infections; Injections, Subcutaneous; Interferon-gamma - administration & dosage; Interferon-gamma - adverse effects; Interferon-gamma - therapeutic use; Interferons; Major Articles; Male; Medical sciences; Mortality; Other diseases. Hematologic involvement in other diseases; Phagocytes; Pharmacology. Drug treatments; Time
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1086/422993

Background. Chronic granulomatous disease (CGD) is a rare disorder of phagocytes in which absent production of superoxide and hydrogen peroxide in phagocytes predisposes patients to bacterial and fungal infections. Infections are dramatically reduced by prophylaxis with antibiotics, antifungals, and interferon-γ (IFN-γ). Methods. Seventy-six patients with CGD were enrolled in an uncontrolled, open-label follow-up study to assess the long-term clinical safety and efficacy of IFN-γ therapy. Patients received IFN-γ subcutaneously 3 times per week. Results. We observed patients for up to 9 years, for a total observation period of 328.4 patient-years. The incidence of serious infections was 0.30 infections per patient-year; for serious bacterial infections, the incidence was 0.18 cases per patient-year, and for serious fungal infections, it was 0.12 cases per patient-year. Thirty-seven percent of patients reported an adverse event, the most common of which was fever. Twenty-six patients withdrew from the study (3 because of adverse events, 15 because of patient preference, and 8 because of transfer to another trial). There were no life-threatening IFN-γ—related adverse events and no discernible effects on growth. The overall mortality rate was 1.5% per patient-year. Conclusion. IFN-γ prophylaxis for CGD appears to be effective and well tolerated over a prolonged period of time.