AFFIRM was a randomized, double-blind, placebo-controlled, phase 3 trial that evaluated efficacy and safety of natalizumab (n = 627) vs. placebo (n = 315) in relapsing-remitting MS. Binocular acuities were measured at low-contrast (1.25%, 2.5%) and high-contrast visual acuity (VA). Improvement was defined as 12-week sustained increases from baseline. Clinically meaningful change for primary analyses was pre-defined as 7-letter improvement for low-contrast acuity and 5-letter improvement for VA based upon previous studies.
Compared to placebo, cumulative probabilities of sustained visual improvement were greater in the natalizumab group by 57%for 2.5%contrast (21.7%vs. 14.0%; HR = 1.57; 95%CI: 1.11-2.22; P = 0.012) and 39%for 1.25%contrast (32.5%vs. 25.0%; HR = 1.39; 95%CI: 1.07-1.82; P = 0.014). The 5- and 10-letter low-contrast assessments did not show treatment differences. High-contrast VA was insensitive to changes over time and treatment effects.
Low-contrast letter acuity detected treatment effects on sustained visual improvement in patients with relapsing MS. The ability to detect visual improvement and loss makes low-contrast acuity an important measure for future trials assessing the impact of therapy on this outcome and the potential of a therapy for neuroprotection and repair.