INTERFERON ALFA-2A IS INEFFECTIVE FOR PATIENTS WITH CHOROIDAL NEOVASCULARIZATION SECONDARY TO AGE-RELATED MACULAR DEGENERATION - RESULTS OFA PROSPECTIVE RANDOMIZED PLACEBO-CONTROLLED CLINICAL-TRIAL

Background: Interferon alfa-2a has been shown to be effective as an an tiangiogenic agent for several systemic human angiogenic disorders and has shown antiangiogenic activity in the laboratory. Objective: To ev aluate the safety and efficacy of interferon alfa-2a for the treatment of choroidal neovascularization secondary to age-related macular dege neration. Methods: A randomized, placebo-controlled, parallel, multice nter double-blind trial was performed at 45 ophthalmic centers worldwi de. Four hundred eighty-one patients were randomly assigned to 4 treat ment groups: placebo or or interferon alfa-2a (Roferon-A), 1.5, 3.0, o r 6.0 million international units (MIU). Visual acuity testing, clinic al examination, fluorescein angiography, and indocyanine green angiogr aphy were evaluated, with the primary end point being a comparison of the number of patients who experienced a loss of 3 lines or more of vi sion at 1 year. Results: At 52 weeks, 40 (38%; 95% confidence interval , 29%-48%) of 105 placebo-treated patients had lost at least 3 lines o f vision (with 12% unavailable for follow-up), compared with 142 (50%; 95% confidence interval, 44%-55%) of 286 in che 3 active treatment gr oups combined. The difference in proportions was not statistically sig nificant. However, a pairwise comparison of these proportions for the placebo group vs the group that received interferon alfa-2a, 6 MIU (wi th 26% unavailable for follow-up), showed a statistically significant difference in favor of the placebo group (P=.02) and a nearly signific ant difference for the placebo vs the 1.5-MIU group (P=.05) (with 16% unavailable for follow-up), again favoring the placebo group. The 3-MI U group (with 22% unavailable for follow-up) did not show a statistica lly significant difference in pairwise comparison (P=.48), suggesting that a dose-response relationship was not evident. Conclusion: Interfe ron alfa-2a provides no benefit as a treatment for choroidal neovascul arization secondary to age-related macular degeneration and may be ass ociated with a poorer visual outcome when given at a dose of 6 MIU. Ho wever, the absence of a clear dose-response relationship raises the po ssibility that the observed differences result from chance.