Effects of Peginterferon Beta-1a on Visual Dysfunction in Multiple Sclerosis

Background: Visual dysfunction is common in patients with RRMS and often accompanied by reduced quality of life. Although patients with RRMS often show similar scores to healthy volunteers on high-contrast (100%-contrast) visual acuity tests, visual dysfunction is consistently seen when using low-contrast (eg 2.5%-contrast) visual acuity charts. Moreover, scores on low-contrast visual acuity correlate with physical and mental impairment. Here, Visual Function Test (VFT) scores were evaluated in the ADVANCE study.

Objectives: To evaluate visual function changes in patients with relapsing remitting multiple sclerosis (RRMS) treated with subcutaneous peginterferon beta-1a in the Phase III ADVANCE study.

Methods: ADVANCE was a 2-year, double-blind, placebo-controlled, Phase III study in patients aged 18–65 years with RRMS. During Year 1, patients were treated with peginterferon beta-1a 125 mcg either every 2 weeks or every 4 weeks or placebo. At the end of Year 1, patients on placebo were re-randomized to peginterferon beta-1a every 2 weeks or every 4 weeks (delayed treatment). At baseline and every 12 weeks during the study, patients were assessed for number of correctly identified letters on the Low-contrast Sloan Letter Chart (out of 60 total) using the 1.25%, 2.5%, and 100% charts of the VFT. VFT changes at week 48 were compared between treated and placebo groups using an analysis of covariance model, adjusted for baseline VFT scores. Correlation analysis utilized Spearman’s rank correlation.

Results: In the subgroup of visually impaired patients with baseline 2.5% VFT scores below median, vision was significantly improved with peginterferon beta-1a every 2 weeks vs placebo at 48 weeks (2.4 vs 1.1; p=0.048 [2.5% VFT]). Overall population changes in 2.5% VFT scores from baseline to 48 weeks trended towards improvement in peginterferon beta-1a every 2 weeks vs placebo patients (0.2 vs -0.5, p=0.194). Across all patient groups at week 48, 2.5% VFT scores were significantly correlated with the Expanded Disability Status Scale (rho=-0.29), Multiple Sclerosis Impact Scale Physical Impact Scores (rho=-0.27), and Psychological Impact Scores (rho=-0.21), the 12-Item Short Form Health Survey Physical Component Summary (rho=0.26) and Mental Component Summary (rho=0.19).

Conclusions: In patients with RRMS with lower 2.5% VFT scores at baseline (below median), acuity was significantly improved following treatment with subcutaneous peginterferon beta-1a vs placebo.