Patterns and predictors of transition between multiple sclerosis phenotypes: A longitudinal analysis

Background Multiple sclerosis (MS) phenotype transitions are challenging to characterize. Our understanding of their predictors is also limited. Objective To investigate the transition between relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) within the Comprehensive Longitudinal Investigation of MS at the Brigham and Women's Hospital (CLIMB) study. Methods This retrospective study included adult people with MS having ≥10-year follow-up data who were classified as RRMS, primary progressive MS, and SPMS (active SPMS [aSPMS]: with relapse; nonrelapsing SPMS [nrSPMS]: no relapses within 2-year pre-index). Demographics, disability scores, and transition predictors were assessed. Results Ninety-seven of 565 people with RRMS (17.2%) transitioned to SPMS, of whom 92.8% ( n = 90/97) were classified as nrSPMS by the final visit. People with RRMS who transitioned to nrSPMS were older (mean age, 53.1 vs. 45.4 years; P < 0.001) and took longer time to transition (mean, 13.0 vs. 7.8 years; P < 0.001) than those who transitioned to aSPMS. Older age at MS onset and a high number of disease-modifying therapy switches were significantly associated with a shorter time-to-nrSPMS transition ( P ≤ 0.001). Conclusion This study provides a comprehensive characterization of MS phenotype transitions, that may enhance clinical decision-making and therapeutic targeting of underlying pathophysiology driving disability in progressive MS.