OTC Antihistamine Clemastine May Accelerate Disability in Those with Progressive MS

Cutting-edge research has unveiled concerning findings regarding the use of clemastine fumarate in those with progressive multiple sclerosis (MS). The study, conducted by a team of researchers from the National Institutes of Health (NIH) and other institutions, revealed that clemastine fumarate, an over-the-counter (OTC) antihistamine thought to have remyelinating potential in MS, may actually accelerate disability accumulation in patients with progressive MS. Results were presented at the Americas Committee for Research and Treatment in Multiple Sclerosis (ACTRIMS) Forum 2024.

Researchers added a clemastine arm to the ongoing TRAP-MS clinical trial (NCT03109288), officially known as "Targeting Residual Activity By Precision, Biomarker-Guided Combination Therapies of Multiple Sclerosis," which is designed to investigate the impact of 4 drugs (pioglitazone, clemastine fumarate, dantrolene, pirfenidone) either given alone or in combination, on MS biomarkers.

• The study included adult participants diagnosed with MS, who were currently taking disease-modifying therapies (DMTs) and who had documented sustained clinical progression of at least 0.5 CombiWISE points per year.
• The objective of the clemastine arm study was to identify cerebrospinal fluid (CSF) remyelination signatures and to collect safety data in those progressing by non-lesional activity.  
• Nine participants had >1 clinical follow-up visit while taking clemastine. CSF was collected before treatment was initiated, as well as 6 months after clemastine treatment and then analyzed using a variety of techniques.

In terms of results, 3 patients increased disability 5-times faster compared to their 18-months “baseline” progression slopes. This outcome prompted the termination of the clemastine arm of the trial owing to safety concerns. Patients taking clemastine exhibited signs of systemic inflammation, as indicated by increased C-reactive protein/erythrocyte sedimentation rate levels and weight gain. Furthermore, proteomic profiling of cerebrospinal fluid highlighted activation of innate immunity, increased purinergic/ATP signaling and enhanced immunogenic cell death, including pyroptosis.