Predictors of response to opicinumab in acute optic neuritis

Objective: The objective of this study was to evaluate prespecified and posthoc analyses in RENEW subgroups to identify participants more likely to ben-efit from opicinumab.Methods: RENEW assessed the efficacy/safety of opici-numab versus placebo in participants with a first unilateral acute opticneuritis (AON) episode. Difference in visual evoked potential (VEP) latency ofthe affected eye at 24 weeks versus the fellow eye at baseline was the primaryendpoint. Interactions between the primary endpoint and prespecified baselinevariables (including age, timing of treatment initiation, and visual impairment)using the median as cut-off were evaluated in the per protocol populationusing analysis of covariance (ANCOVA); subgroups based on preexisting brainT2 lesion volume were also analyzed. Interactions between the primary end-point and retinal ganglion cell layer/inner plexiform layer (RGCL/IPL) andretinal nerve fiber layer (RNFL) thickness were assessed post hoc as wasweight gain by treatment.Results: Treatment benefit of opicinumab (n=33)over placebo (n=36) on the primary endpoint was greatest in participantsolder than the median age at baseline (≥33 years); the difference versus pla-cebo for baseline age≥33 years was14.17 msec [P=0.01] versus0.89 msec for baseline age<33 years, [P=0.87]). Post hoc analysis showedthat VEP latency recovery was significantly associated with less RGCL/IPLthinning (P=0.0164), occurring early on.Interpretation: Age was the stron-gest prespecified baseline characteristic associated with a treatment effect ofopicinumab. A strong association between VEP latency recovery at week 24and early RGCL/IPL preservation was observed.