Assessment of Opicinumab in Acute Optic Neuritis Using Multifocal Visual Evoked Potential

A Klistorner, Y Chai, L Leocani, P Albrecht, O Aktas, H Butzkueven, T Ziemssen, F Ziemssen, J Frederiksen, L Xu, D Cadavid, on behalf of RENEW MF-VEP Investigators

Research output: Contribution to journalArticle

Abstract

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. © 2018, The Author(s).
Original languageEnglish
Pages (from-to)1159-1171
Number of pages13
JournalCNS Drugs
Volume32
Issue number12
DOIs
Publication statusPublished - 2018

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Optic Neuritis
Visual Evoked Potentials
Visual Pathways
Placebos
Optic Nerve Injuries
Population
Therapeutics
Visual Fields
Multicenter Studies
Central Nervous System
Observation
Clinical Trials

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Klistorner, A., Chai, Y., Leocani, L., Albrecht, P., Aktas, O., Butzkueven, H., ... Investigators, O. B. O. RENEW. MF-VEP. (2018). Assessment of Opicinumab in Acute Optic Neuritis Using Multifocal Visual Evoked Potential. CNS Drugs, 32(12), 1159-1171. https://doi.org/10.1007/s40263-018-0575-8

Assessment of Opicinumab in Acute Optic Neuritis Using Multifocal Visual Evoked Potential. / Klistorner, A; Chai, Y; Leocani, L; Albrecht, P; Aktas, O; Butzkueven, H; Ziemssen, T; Ziemssen, F; Frederiksen, J; Xu, L; Cadavid, D; Investigators, on behalf of RENEW MF-VEP.

In: CNS Drugs, Vol. 32, No. 12, 2018, p. 1159-1171.

Research output: Contribution to journalArticle

Klistorner, A, Chai, Y, Leocani, L, Albrecht, P, Aktas, O, Butzkueven, H, Ziemssen, T, Ziemssen, F, Frederiksen, J, Xu, L, Cadavid, D & Investigators, OBORENEWMF-VEP 2018, 'Assessment of Opicinumab in Acute Optic Neuritis Using Multifocal Visual Evoked Potential', CNS Drugs, vol. 32, no. 12, pp. 1159-1171. https://doi.org/10.1007/s40263-018-0575-8
Klistorner, A ; Chai, Y ; Leocani, L ; Albrecht, P ; Aktas, O ; Butzkueven, H ; Ziemssen, T ; Ziemssen, F ; Frederiksen, J ; Xu, L ; Cadavid, D ; Investigators, on behalf of RENEW MF-VEP. / Assessment of Opicinumab in Acute Optic Neuritis Using Multifocal Visual Evoked Potential. In: CNS Drugs. 2018 ; Vol. 32, No. 12. pp. 1159-1171.
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title = "Assessment of Opicinumab in Acute Optic Neuritis Using Multifocal Visual Evoked Potential",
abstract = "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. {\circledC} 2018, The Author(s).",
author = "A Klistorner and Y Chai and L Leocani and P Albrecht and O Aktas and H Butzkueven and T Ziemssen and F Ziemssen and J Frederiksen and L Xu and D Cadavid and Investigators, {on behalf of RENEW MF-VEP}",
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T1 - Assessment of Opicinumab in Acute Optic Neuritis Using Multifocal Visual Evoked Potential

AU - Klistorner, A

AU - Chai, Y

AU - Leocani, L

AU - Albrecht, P

AU - Aktas, O

AU - Butzkueven, H

AU - Ziemssen, T

AU - Ziemssen, F

AU - Frederiksen, J

AU - Xu, L

AU - Cadavid, D

AU - Investigators, on behalf of RENEW MF-VEP

PY - 2018

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N2 - 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. © 2018, The Author(s).

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. © 2018, The Author(s).

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DO - 10.1007/s40263-018-0575-8

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JO - CNS Drugs

JF - CNS Drugs

SN - 1172-7047

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