PMID- 30267385 OWN - NLM STAT- MEDLINE DCOM- 20191014 LR - 20201103 IS - 1179-1934 (Electronic) IS - 1172-7047 (Print) IS - 1172-7047 (Linking) VI - 32 IP - 12 DP - 2018 Dec TI - Assessment of Opicinumab in Acute Optic Neuritis Using Multifocal Visual Evoked Potential. PG - 1159-1171 LID - 10.1007/s40263-018-0575-8 [doi] AB - BACKGROUND: Multifocal visual evoked potential (MF-VEP) assesses a wider visual field than full-field VEP (FF-VEP) and potentially offers a more precise analysis of optic nerve injury and repair following optic neuritis. MF-VEP may offer advantages over FF-VEP as an endpoint in clinical trials of remyelinating therapies. OBJECTIVE: MF-VEP testing was used to study changes in visual pathways in 48% of RENEW [phase II, opicinumab (anti-LINGO-1; BIIB033) vs. placebo after first acute unilateral optic neuritis] participants. METHODS: This exploratory MF-VEP RENEW substudy compared mean outcomes at weeks 24 and 32 among participants in the intent-to-treat (ITT; n = 39; 72% female; mean age: 32.3 years) and per-protocol (PP; n = 31; 71% female; mean age: 32.2 years) populations in affected and fellow eye latency from fellow eye baseline latency and affected and fellow eye amplitude from their own baselines. Treatment differences were evaluated using analysis of covariance (week 24) and a mixed-effect model of repeated measures (week 32). Last observation carried forward was used to impute missing data at week 24. RESULTS: A trend for improvement in affected eye MF-VEP latency with opicinumab versus placebo was seen in the ITT and PP populations at weeks 24 and 32. Both treatment groups in the ITT population experienced partial recovery of amplitude in the affected eye at week 32. Notably, the mean change in fellow eye amplitude at weeks 24 and 32 was - 17.57 and - 31.41 nanovolts (nV) in placebo but only - 0.59 and 1.93 nV in the opicinumab group [differences at weeks 24 and 32: 16.98 nV (p = 0.050) and 33.33 nV (p < 0.01), respectively]. CONCLUSION: Results from this substudy showed advantages of MF-VEP over FF-VEP in multicenter studies of central nervous system reparative therapies and provide novel evidence that fellow eye visual pathway amplitude loss occurs after optic neuritis but can potentially be prevented by opicinumab treatment. REGISTRATION: ClinicalTrials.gov identifier NCT01721161. FAU - Klistorner, Alexander AU - Klistorner A AD - Department of Ophthalmology, University of Sydney, Sydney, NSW, Australia. FAU - Chai, Yi AU - Chai Y AD - Biogen, Cambridge, MA, USA. FAU - Leocani, Letizia AU - Leocani L AD - Neurological Department and Experimental Neurophysiology Unit, Institute of Experimental Neurology (INSPE), University Hospital-IRCCS San Raffaele, Milan, Italy. FAU - Albrecht, Philipp AU - Albrecht P AD - Department of Neurology, Medical Faculty, Heinrich-Heine-Universitat Dusseldorf, Dusseldorf, Germany. FAU - Aktas, Orhan AU - Aktas O AD - Department of Neurology, Medical Faculty, Heinrich-Heine-Universitat Dusseldorf, Dusseldorf, Germany. FAU - Butzkueven, Helmut AU - Butzkueven H AD - Department of Neuroscience, Central Clinical School, Monash University Alfred Campus, Melbourne, VIC, Australia. FAU - Ziemssen, Tjalf AU - Ziemssen T AD - MS Center Dresden, Center of Clinical Neuroscience, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden, Germany. FAU - Ziemssen, Focke AU - Ziemssen F AD - Center for Ophthalmology, Eberhard Karls University of Tubingen, Tubingen, Germany. FAU - Frederiksen, Jette AU - Frederiksen J AD - Department of Neurology, Rigshospitalet Glostrup and University of Copenhagen, Copenhagen, Denmark. FAU - Xu, Lei AU - Xu L AD - Biogen, Cambridge, MA, USA. FAU - Cadavid, Diego AU - Cadavid D AD - Biogen, Cambridge, MA, USA. cadavid.diego@gmail.com. AD - Fulcrum Therapeutics, Cambridge, MA, USA. cadavid.diego@gmail.com. CN - RENEW MF-VEP Investigators LA - eng SI - ClinicalTrials.gov/NCT01721161 PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - New Zealand TA - CNS Drugs JT - CNS drugs JID - 9431220 RN - 0 (Antibodies, Monoclonal) RN - 0 (Immunologic Factors) RN - WX1WTN0Y15 (opicinumab) SB - IM MH - Acute Disease MH - Adult MH - Antibodies, Monoclonal/*therapeutic use MH - Evoked Potentials, Visual/*drug effects MH - Female MH - Humans MH - Immunologic Factors/*therapeutic use MH - Male MH - Optic Neuritis/*drug therapy/*physiopathology MH - Photic Stimulation MH - Time Factors MH - Visual Fields/drug effects MH - Visual Perception/drug effects/physiology MH - Young Adult PMC - PMC6280853 COIS- Alexander Klistorner has nothing to disclose. Yi Chai was a full-time employee of Biogen during the performance of the clinical trial, data analysis, and initial drafting of the manuscript. Letizia Leocani has received honoraria for consulting and/or speaking activities from Biogen, Merck, Roche, and Teva; research support from Biogen, Merck, and Novartis; and travel support from Almirall, Biogen, Merck, Novartis, and Roche. Philipp Albrecht has received grants from Biogen, the Dr. Robert Pfleger Foundation, Ipsen, Merz, and Novartis; received non-financial support from Bayer HealthCare, Ipsen, Merck, Merz, Novartis, Roche, and Teva; participated in advisory boards for Allergan, Ipsen, and Merz; and received personal fees from Allergan, Bayer HealthCare, Biogen, Ipsen, Novartis, Roche, and Teva, outside of the submitted work. Orhan Aktas has received advisor fees or honoraria from Almirall, Bayer HealthCare, Biogen, MedImmune, Merck, Novartis, and Teva; and research support from Bayer HealthCare, Biogen, Novartis, Roche, and Teva. Helmut Butzkueven has participated in advisory boards for Biogen, Merck, Novartis, and Teva; received consulting fees from Novartis and Oxford Pharmagenesis; lecture fees from Biogen; received payment for development of educational presentations from Biogen, Merck, and Novartis; and research grants from Biogen and Novartis, outside of the submitted work. Tjalf Ziemssen has received consulting fees from Almirall, Bayer HealthCare, Biogen, Genzyme, GlaxoSmithKline, Merck Serono, MSD, Novartis, Sanofi-Aventis, Synthon, and Teva; and research support from Bayer HealthCare, Biogen, Merck Serono, Novartis, Sanofi-Aventis, and Teva. Focke Ziemssen has received consulting fees from Alimera, Allergan, Bayer HealthCare, Boehringer Ingelheim, Novartis, and Roche; and research support from Novartis. Jette Frederiksen has participated in scientific advisory boards for Almirall, Biogen, Genzyme, Merck Serono, Novartis, Sanofi-Aventis, and Teva; received speaker honoraria from Biogen, Merck Serono, Santhera, and Teva; and been an advisor on preclinical development for Takeda, outside of the submitted work. Lei Xu was a full-time employee of Biogen during the performance of the clinical trial, data analysis, and initial drafting of the manuscript. Diego Cadavid was a full-time employee of Biogen during the performance of the clinical trial and a full-time employee of Fulcrum Therapeutics during submission of the manuscript; the work is not related to his employment in Fulcrum Therapeutics. He has patent WO 2016112270 A1: Lingo-1 antagonists and uses for treatment of demyelinating disorders, which is assigned to Biogen. FIR - Butzkueven, Helmut IR - Butzkueven H FIR - Garrick, Ray IR - Garrick R FIR - Vanopdenbosch, Ludo IR - Vanopdenbosch L FIR - Frederiksen, Jette IR - Frederiksen J FIR - Aktas, Orhan IR - Aktas O FIR - Albrecht, Philipp IR - Albrecht P FIR - Ziemssen, Focke IR - Ziemssen F FIR - Ziemssen, Tjalf IR - Ziemssen T FIR - Comi, Giancarlo IR - Comi G FIR - Dalmau, Bernardo Sanchez IR - Dalmau BS FIR - Andersson, Magnus IR - Andersson M FIR - Plant, Gordon T IR - Plant GT FIR - Matthews, Tim IR - Matthews T FIR - Williams, Graeme IR - Williams G EDAT- 2018/09/30 06:00 MHDA- 2019/10/15 06:00 PMCR- 2018/09/28 CRDT- 2018/09/30 06:00 PHST- 2018/09/30 06:00 [pubmed] PHST- 2019/10/15 06:00 [medline] PHST- 2018/09/30 06:00 [entrez] PHST- 2018/09/28 00:00 [pmc-release] AID - 10.1007/s40263-018-0575-8 [pii] AID - 575 [pii] AID - 10.1007/s40263-018-0575-8 [doi] PST - ppublish SO - CNS Drugs. 2018 Dec;32(12):1159-1171. doi: 10.1007/s40263-018-0575-8.