BARCELONA—Anti-LINGO-1 improved full-field visual evoked potential (FF-VEP) latency of the eye affected by acute optic neuritis relative to placebo, consistent with improved remyelination, according to a study reported at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). This latency recovery was greater in older subjects, subjects given the first dose earlier, and subjects with more severe pretreatment visual impairment.
In a primary efficacy analysis of the RENEW study, Orhan Aktas, MD, of Heinrich-Heine-Universität in Düsseldorf, Germany, and colleagues demonstrated an improvement versus placebo in optic nerve latency (-7.55 ms at week 24; -9.13 ms at week 32) consistent with remyelination in subjects with acute optic neuritis.
Research subjects ages 18 to 50 with a first unilateral acute optic neuritis episode were treated with high-dose steroids, then randomized to 100 mg/kg anti-LINGO-1 IV or placebo once every four weeks (ie, six doses) and followed to week 32. Optic nerve latency was measured using FF-VEP in the affected eye versus the baseline value for the unaffected eye. Between-treatment comparisons were evaluated by ANCOVA in the per-protocol population, defined as subjects who completed the study and did not miss more than one study dose or receive disease-modifying therapy for multiple sclerosis. Further analyses of latency recovery at week 24 (affected eye FF-VEP latency ≤10% worse than baseline of fellow eye) and efficacy stratified by prespecified baseline characteristics using the median as the cutoff were performed.
FF-VEP latency recovery in the affected eye versus baseline of the fellow eye was compared between 33 subjects who received anti-LINGO-1 and 36 treated with placebo. At week 24, 24 subjects had normal or mildly prolonged FF-VEP latency, 15 from the anti-LINGO-1 and nine from the placebo group. Assessment of subjects stratified by prespecified baseline characteristics showed that improvement in FF-VEP latency in the affected eye at week 24 with anti-LINGO-1 was greater in the following patient subgroups: age 33 or older (difference vs placebo, -14.17 ms compared with -0.89 ms in subjects younger than 33); those who received treatment less than 25 days from the onset of acute optic neuritis (-9.01 ms vs -6.68 ms for those receiving treatment more than 25 days after acute optic neuritis onset); and those who had a high-contrast visual acuity score less than 49 (-10.92 ms vs -4.14 ms for a score of 49 or more). None of the subgroup-by-treatment interactions reached statistical significance due to the small sample size.