Insufficient Evidence to Suggest Discontinuation of MS Disease-Modifying Therapies Leads to Worsened Patient-Reported Outcomes

Wing Hee Fung

Data from the randomized controlled DOT-MS study showed stable patient-reported outcome measure (PROM) results between individuals with multiple sclerosis (MS) who continued on with their disease-modifying therapy (DMT) and those who discontinued. The study was ultimately discontinued early because of inflammatory disease activity in the discontinuation group above the predefined limit, leaving investigators to conclude that there is insufficient evidence between the discontinuation of DMTs and worsening of PROMs.¹

These data were presented in a late-breaker at MSMilan 2023, the joint ECTRIMS-ACTRIMS meeting, held October 11-13, in Milan, Italy, by Wing Hee Fung, a PhD candidate at Amsterdam University Medical Centers. Although the study was prematurely discontinued, participants were offered to restart their DMT and will be followed up during the observational phase, which lasts 2 years.

The study featured 89 participants with relapsing-onset MS who had at least 5 years of no relapses and no significant MRI activity. Patients were randomized to either discontinuing DMT (n = 45) or continuing on with treatment, which included any of the interferons, glatiramer acetate, dimethyl fumarate, and teriflunomide. In both groups, most patients had relapsing-remitting MS, with fewer numbers of individuals with secondary progressive MS. Patients were followed up for a median of 19.0 (IQR, 14.01-24.0) months. In the discontinuation group, significant disease activity occurred in 8 individuals (17.8%) with a median of 12.0 (IQR, 6.0-16.5) months to their activity occurring.

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Investigators observed several PROMs, including Checklist Individual Strength, Short Form health survey-36, Multiple Sclerosis Impact Scale, and treatment satisfaction. Over time, these PROMs remained stable in both groups. Only MSIS-29 physical component was worsened at the end of the study compared with baseline in the discontinuation group, however no difference was seen between the 2 groups.

There are several reasons for why patients may choose to discontinue DMTs, safety being one. Several approved agents come with associated adverse events (AEs) that can become too cumbersome for patients, especially if their relapses have become manageable. Additionally, the overall costs of DMTs have been rising rapidly over the past 2 decades, including out-of-pocket costs for patients and healthcare system costs. As patients get older, and their income sources and health insurance coverage becomes more limited, awareness of these costs becomes increasingly important.²

The research literature on discontinuation of DMTs has grown, but led to nixed results, mainly because of differences in trial design. Some studies have been observational and retrospective, while others mainly observe factors associated with return of disease activity if DMT is halted for any of a variety of reasons. Numerous discontinuation studies do not include information on disease stability or age, whereas others have considered discontinuation in individuals in patients who were stable for defined periods of time with particular age cutoffs. Similar to Fung et al’s work, almost all studies have looked at first-generation medicines.

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REFERENCES
1. Coerver EME, Fung WH, Beukelaar JD, et al. Patient-reported outcomes in discontinuation of first-line disease-modifying therapy in stable multiple sclerosis (DOT-MS): results of a multicenter randomized controlled trial. Presented at: MSMilan; October 11-13, 2023; Milan, Italy. POSTER 791
2. Shah AA, Corboy JR. Discontinuing disease-modifying therapies in multiple sclerosis. Practical Neurology. February 2022. Accessed October 18, 2023. https://practicalneurology.com/articles/2022-feb/discontinuing-disease-modifying-therapies-in-multiple-sclerosis