Outcome measures for trials of remyelinating agents in multiple sclerosis: retrospective longitudinal analysis of visual evoked potential latency

Abstract

Prolonged P100 latencies in eyes never affected by clinical ON remain stable and thus can be used as surrogate outcome measure for remyelination trials.

Clemastine fumarate as a remyelinating therapy for multiple sclerosis (ReBUILD): a randomised, controlled, double-blind, crossover trial

“…Furthermore, 16% of group 1 and 26% of group 2 showed a latency improvement of more than 6 ms while on treatment compared with 3% of group 1 and 6% of group 2 while on placebo (figure 2) in a post-hoc analysis done based on lab standards of significant interocular differences and previous scientific literature. 33,34 Patients also showed evidence of improvement in LCLA for the period on treatment, with an increase of 0·9 letters per eye (95% CI -0·1 to 1·9; p=0·085; figure 3) using the crossover analysis; however, this observation did not meet the prespecified threshold of statistical significance. An additional post-hoc analysis done by assessing the LCLA outcome with the delayed-treatment model suggested an increase of 1·6 letters per eye (0·2 to 3·0; p=0·022).…”

“…However, we consider the delayedtreatment analysis to provide a more realistic appraisal of the magnitude of the therapeutic benefit achieved with clemastine fumarate at this dose. Additionally, in a post-hoc analysis that evaluated the VEP data using a 6 ms improvement threshold (which, based on experience and previous literature, 33,34 would not be anticipated to be due to measurement error), clemastine fumarate treatment out performed placebo in both periods of the trial.…”

Safety and efficacy of opicinumab in acute optic neuritis (RENEW): a randomised, placebo-controlled, phase 2 trial

“…To overcome this limitation in the design of the RENEW study, we calculated the diff erence in aff ected eye VEP latency over time using the unaff ected fellow eye baseline value as the pretreatment normal reference value. 12,16 Although variable between individuals, 11 VEP usually has a very small inter-eye latency variation in the absence of disease pathology and is highly reproducible for sequential testing under standardised testing conditions. 12,16,17 To ensure that the baseline of the fellow eye was normal, participants with a diagnosis of multiple sclerosis or ophthalmological disorders were excluded and the fellow eye had to have a normal VEP at screening.…”

Comparison of visual evoked potential parameters in acute optic neuritis

“…Warto podkreślić, że w przebiegu pozagałkowego ON na tle SM wydłużenie latencji fali P100 utrzymuje się pomimo poprawy ostrości wzroku i zmniejsza się stopniowo w ciągu pierwszych 6 miesięcy do 4 lat od epizodu ON. Sugeruje to ograniczoną zdolność naprawczej remielinizacji aksonów [21,22]. Równocze-śnie zaznacza się subkliniczne wydłużenie latencji P100 w towarzyszącym, "zdrowym" oku, co ma znaczenie prognostyczne i pozwala zidentyfikować pacjentów, u których ryzyko rozwoju SM w przyszłości jest zwiększone [23,24], chociaż nie wszyscy autorzy zgadzają się z tym poglądem [26].…”