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

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.

Validation of the World Health Organization Disability Assessment Schedule II (WHODAS-II) in patients with multiple sclerosis.

BACKGROUND: The World Health Organization Disability Assessment Schedule (WHODAS-II) is a widely used generic assessment instrument for health and disability. However, a specific psychometric evaluation for this scale in multiple sclerosis (MS) is lacking. This study is aimed at the assessment of the psychometric properties of the WHODAS-II in MS with Cronbach's α and modern Rasch-model analyses. METHODS: The WHODAS-II was administered to 136 consecutively recruited MS patients. Several indexes of fit to the Rasch model were evaluated in order to assess internal construct validity. Internal consistency was assessed with Cronbach's α and the Person Separation Index (PSI). External validity was evaluated by analyzing correlations between the WHODAS-II and the Multiple Sclerosis Quality of Life-54 (MSQoL-54). RESULTS: Classical reliability indexes (Cronbach's α and intraclass correlation) showed good to excellent reliability for most of the subscales and for the total scale (α = 0.93). The total scale both with (36 items) or without (32 items) work items reached good fit to the Rasch model (PSI = 0.83). However, analysis of the subscales could resolve only four subscales out of seven. CONCLUSIONS: The WHODAS-II is a reliable and valid instrument for the assessment of patient-reported disability in MS, with some limitations including some item redundancy and questionable reliability of some subscales.