Long-term interferon-gamma therapy for patients with chronic granulomatous disease.
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- gamma (IFN-gamma ).


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-gamma therapy. Patients received IFN-gamma 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-gamma-related adverse events and no discernible effects on growth. The overall mortality rate was 1.5% per patient-year.


CONCLUSIONS
IFN-gamma prophylaxis for CGD appears to be effective and well tolerated over a prolonged period of time.
Marciano
Beatriz E
BE
Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.
Wesley
Robert
R
De Carlo
Ellen S
ES
Anderson
Victoria L
VL
Barnhart
Lisa A
LA
Darnell
Dirk
D
Malech
Harry L
HL
Gallin
John I
JI
Holland
Steven M
SM
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006105:Granulomatous Disease, Chronic / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007223:Infant; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D013995:Time
D007371:Interferon-gamma