IFN- α Antibodies in Patients with Age-Related Macular Degeneration Treated with Recombinant Human IFN- α 2a

We tested for development of binding and neutralizing antibodies to interferon-α (IFN-α) during IFN-α2a therapy of patients with age-related macular degeneration (AMD) of the eyes. Antibodies were investigated retrospectively in sera of 34 patients treated with 3 × 10⁶ IU IFN-α2a (Roceron-A^®, Hoffmann La-Roche, Basel, Switzerland) three times weekly for periods of 8-16 weeks with or without a drug-free 4-12-week intermission. Additionally, 10 patients were investigated prospectively; 7 received 1.5-6 × 10⁶ IU IFN-α2a three times weekly for 12 months, and 3 received placebo. Binding antibodies were tested by molecular size and protein G affinity chromatography using ¹²⁵I-IFN-α2a. Neutralizing activities were tested by antiviral neutralization bioassay. IgG antibodies were detected in 24 of 34 IFN-α2a-treated patients (71%). Significantly higher anti-IFN-α levels were observed in patients who after discontinuation were readministered IFN-α2a (p < 0.02). Three of the IFN-α2a-treated patients in the prospective study had high and 1 had low antibody titers. Neutralizing antibody titers were high against IFN-α2a and IFN-α2c and low against lymphoblastoid and leukocyte IFN-α. Impaired clinical responses were observed in antibody-positive patients (p < 0.01). The development of neutralizing anti-IFN-α antibodies in patients with AMD during recombinant human IFN-α therapy may explain the often poor clinical effect of IFN-α treatment.