OBJECTIVE: The objective of this study was to evaluate prespecified and post hoc analyses in RENEW subgroups to identify participants more likely to benefit from opicinumab. METHODS: RENEW assessed the efficacy/safety of opicinumab versus placebo in participants with a first unilateral acute optic neuritis (AON) episode. Difference in visual evoked potential (VEP) latency of the affected eye at 24 weeks versus the fellow eye at baseline was the primary endpoint. Interactions between the primary endpoint and prespecified baseline variables (including age, timing of treatment initiation, and visual impairment) using the median as cut-off were evaluated in the per protocol population using analysis of covariance (ANCOVA); subgroups based on preexisting brain T2 lesion volume were also analyzed. Interactions between the primary endpoint and retinal ganglion cell layer/inner plexiform layer (RGCL/IPL) and retinal nerve fiber layer (RNFL) thickness were assessed post hoc as was weight gain by treatment. RESULTS: Treatment benefit of opicinumab (n = 33) over placebo (n = 36) on the primary endpoint was greatest in participants older than the median age at baseline (≥33 years); the difference versus placebo for baseline age ≥33 years was -14.17 msec [P = 0.01] versus -0.89 msec for baseline age <33 years, [P = 0.87]). Post hoc analysis showed that VEP latency recovery was significantly associated with less RGCL/IPL thinning (P = 0.0164), occurring early on. INTERPRETATION: Age was the strongest prespecified baseline characteristic associated with a treatment effect of opicinumab. A strong association between VEP latency recovery at week 24 and early RGCL/IPL preservation was observed.

Biogen Cambridge Massachusetts

Center for Ophthalmology Eberhard Karls University of Tuebingen Tuebingen Germany

Charles University Prague Czech Republic

Department of Neurology AZ Sint Jan Brugge Oostende AV Brugge Belgium

Department of Neurology Medical Faculty Heinrich Heine Universität Düsseldorf Düsseldorf Germany

Department of Neurosciences Drugs and Child's Health University of Florence Florence Italy

Departments of Neurology Population Health and Ophthalmology New York University School of Medicine New York New York

Moorfields Eye Hospital and The National Hospital for Neurology and Neurosurgery London United Kingdom

MS Center Dresden Center of Clinical Neuroscience University Hospital Carl Gustav Carus Dresden University of Technology Dresden Germany

University of Ottawa and the Ottawa Hospital Research Institute Ottawa Ontario Canada

Vita Salute San Raffaele University Milan Italy

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