Therapy Choices and Outcomes in Newly Diagnosed Multiple Sclerosis

Background and ObjectivesProspective multinational studies integrating imaging and soluble biomarkers in early multiple sclerosis (MS) are limited. The MultipleMS study compared 2-year clinical, radiologic, and biomarker outcomes across disease-modifying therapies (DMTs) in newly diagnosed MS using harmonized follow-up. MethodsAdults aged 18–50 years with newly diagnosed relapsing or progressive MS and no prior DMT exposure were enrolled at 9 European centers (September 2017–December 2020). Participants were categorized by initial therapy into injectable platform (interferon-beta, glatiramer acetate), oral platform (dimethyl fumarate, teriflunomide), high-efficacy therapies (fingolimod, cladribine, natalizumab, alemtuzumab), B-cell–depleting therapies ([BCDTs]; rituximab, ocrelizumab), or no treatment. Primary outcomes were annualized relapse rate (months 0–24), change in T2 lesion volume (baseline to month 24 [M24]), and serum neurofilament light chain (sNfL) Z-scores at M24. Secondary outcomes included serum glial fibrillary acidic protein (sGFAP) Z-scores, change in Expanded Disability Status Scale (EDSS), and treatment persistence at M24. Analyses used an intention-to-treat approach with adjustment for demographic, baseline disease characteristics, and study center. ResultsOf 509 participants, 455 (89.4%) completed follow-up; the mean age was 33.0 years (interquartile range [IQR] 27.7–40.8), 63.9% were women, the median disease duration was 0.66 years (IQR 0.26–2.14), and the median baseline EDSS was 1.5 (IQR 1.0–2.0). Initial therapies included injectable platform (n = 87, 17.1%), oral platform (n = 152, 29.9%), high efficacy (n = 79, 15.5%), BCDT (n = 101, 19.8%), and untreated (n = 90, 17.7%). Compared with oral platform therapies, BCDT was associated with lower relapse incidence (incidence rate ratio 0.38; 95% CI 0.15–0.92) and greater T2 lesion volume reduction (volume ratio 0.87; 95% CI 0.76–0.99), with similar trends for high-efficacy therapies. Changes in EDSS and sNfL did not differ between groups. sGFAP Z-scores decreased modestly overall, with larger reductions in the oral platform group and relatively higher levels in BCDT and high-efficacy groups. Treatment persistence was higher with BCDT (93.8% vs 72.3%). DiscussionBCDT and high-efficacy therapies exerted greater effects on acute inflammatory than progression-related outcomes, suggesting differential impacts on MS disease processes. Limitations include the observational design and limited follow-up. Trial Registration InformationEudraCT 2017-002634-24, registered on July 06, 2017. First patient enrolled September 29, 2017.