Systematic Review on the Wearing-off Phenomenon of Disease-modifying Therapies in Managing Multiple Sclerosis
Olorungbami Anifalaje1, Aliu Yakubu2, Oluwakemi Olalude3, Francess Adeyemi4, Oreoluwa Morakinyo2, Abdulmalik Makanjuola5
1Dumfries and Galloway Royal Infirmary, 2University of Texas Medical Branch, 3Lagos State University, 4Afe Babalola University, 5Public Health Ontario
Objective:
To conduct a systematic review of the available evidence on the "wearing-off" phenomena associated with disease-modifying treatments (DMTs) in patients with multiple sclerosis, with a focus on clinical symptoms, prevalence, and influence on treatment adherence and quality of life
Background:
Multiple sclerosis (MS) is a progressive neurological disorder managed with Disease Modifying Therapies (DMTs). While these therapies improve outcomes, monoclonal antibody-based DMTs face challenges such as the wearing-off phenomenon. Despite increasing recognition, this phenomena is still poorly understood, demanding a comprehensive evidence synthesis. This systematic review is the first to examine the wearing-off phenomena in MS patients treated with monoclonal antibody therapy.
Design/Methods:
A systematic review and meta-analysis was conducted following PRISMA guidelines. The primary outcome was the difference in Expanded Disability Status Scale (EDSS) ratings between patients with and without the wearing-off phenomenon. The secondary outcome looked at the relationship between disease duration, DMT regimen, and wearing-off symptoms.
Results:
Fourteen studies involving 1752 participants met the inclusion criteria. The prevalence of the wearing-off phenomenon was 54.02%, predominantly manifesting as fatigue, walking difficulties, and cognitive impairment. No significant associations were observed between wearing-off symptoms and EDSS scores (SMD = 0.04, 95% CI:0.44 to 0.52, p = 0.8310) or disease duration (SMD = -0.26, 95% CI:1.86 to 1.33, p = 0.6985). Extended Interval Dosing did not significantly reduce the risk of the wearing-off phenomenon compared to Standard Interval Dosing (RR = 0.88, 95% CI: 0.44 to 1.57, p = 0.6049).
Conclusions:
Despite its high prevalence, the wearing-off phenomenon correlates with EDSS score or disease duration. No statistically significant association was found with EDSS score or disease duration. Further longitudinal studies are needed to find the underlying pathophysiology, identify reliable biomarkers, and develop targeted interventions to improve patient outcomes and treatment satisfaction.
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