OBJECTIVES: Disease-modifying therapies (DMTs) reduce the activity and progression of multiple sclerosis (MS) with high-efficacy DMTs defined as those that reduce relapses by 50%. While several studies have investigated discontinuation rates of high-efficacy DMTs, there are no published reviews synthesizing their results. Our objective was to identify the rates and reasons for discontinuing high-efficacy DMTs among adult patients with MS.

METHODS: In this targeted literature review, we included observational studies published in English between January 2020 and January 2024 that were conducted on adult patients with MS taking high-efficacy DMTs and had reported outcomes of rates and/or reasons for discontinuation of high-efficacy DMTs. We identified and screened the titles/abstracts of 210 articles and full texts of 29 studies.

RESULTS: We included 14 studies: 10 reported discontinuation rates and reasons while four reported only discontinuation rates. These studies varied widely with sample sizes between 29-1,934 participants per high-efficacy DMT and treatment follow-up spanning 11.8-54 months with most in the range of 12-24 months. After 12-24 months of follow-up, discontinuation rates were 54.8% for alemtuzumab, 34.4-45.0% for natalizumab, 25.5% for ofatumumab, 1.0-25.0% for ocrelizumab, and 4.3-9.0% for cladribine. Alemtuzumab, natalizumab, and cladribine were primarily discontinued for medical reasons. Ocrelizumab was largely discontinued for intolerability. Ofatumumab did not have reported discontinuation reasons. Alemtuzumab and natalizumab had the highest rates of discontinuation after 12-24 months and were both primarily discontinued due to medical reasons, such as clinical relapses or disability progression.

CONCLUSIONS: Treatment efficacy was the driving factor in the discontinuation of high-efficacy DMTs compared to intolerability or non-medical reasons after 12-24 months. The included studies were heterogeneous in terms of length of follow-up, sample sizes, and definitions for discontinuation. Future studies should continue to explore discontinuation trends among newer high-efficacy DMTs, including ofatumumab and ublituximab, and utilize a consistent definition for DMT discontinuation.