JAN 11, 2018
Comprehensive Ophthalmology, Neuro-Ophthalmology/Orbit
This phase 2 clinical trial (ReBUILD) evaluated the use of clemastine fumarate—a first-generation antihistamine capable of inducing oligodendrocyte differentiation—as a remyelinating therapy for patients with multiple sclerosis.
Researchers enrolled 50 patients with chronic multiple sclerosis in this single center, double-blind, randomized, placebo-controlled, crossover trial. They randomly assigned participants to clemastine fumarate for 90 days followed by placebo for 60 days (25 patients), or to a placebo for 90 days followed by clemastine fumarate for 60 days (25 patients). The primary outcome was shortening of P100 latency delay on visual evoked potentials (VEP).
Clemastine fumarate reduced the latency delay by 1.7 ms/eye on VEP (p=0.0048). There was a trend toward improvement in low-contrast letter acuity. This trend reached significance in a post-hoc delayed-treatment analysis, with an increase of 1.6 letters per eye (P=0.022). No changes were observed on MRI or OCT. Participants reported no serious adverse events, though some experienced fatigue with treatment.
While the study produced promising results, it has a few limitations. The primary outcome was visual function, but only 56% of participants had a history of optic neuritis. The post-hoc analysis suggests that more robust results might have been obtained from a cohort comprised solely of patients with prior optic neuritis. In addition, visual field data might have helped detect possible changes in visual function. Lastly, the mild improvements in VEP latency and low-contrast letter acuity were small and unlikely to provide clinically meaningful benefits to the patient.
Current treatments for multiple sclerosis focus on preventing demyelinating events; no existing therapies promote remyelination after damage has already occurred. This trial has therefore garnered a lot of excitement.
Regardless of its potential shortcomings, this is the first randomized controlled trial to show the efficacy of a drug that reverses chronic demyelination in people with multiple sclerosis. Larger trials are needed to confirm these results, dissect the drug’s mechanism of action, optimize dosing and determine the most effective treatment duration. It furthermore remains unclear whether these improvements will be sustained beyond the study period. In summary, this trial hints at the promise of future treatments for multiple sclerosis and other demyelinating diseases, but research in this area is far from the finish line.