Association of Sustained Immunotherapy with Disability Outcomes in Patients with Active Secondary Progressive Multiple Sclerosis

Abstract

Question Are clinical and demographic factors associated with the rate at which disability accumulates in secondary progressive multiple sclerosis, and is immunotherapy associated with a slower accumulation of disability among patients with active secondary progressive multiple sclerosis? Findings In this cohort study of 1621 patients with secondary progressive multiple sclerosis, relapses during the secondary progressive disease stage were associated with a faster rate of disability accumulation. Immunotherapies were associated with reductions in disability accumulation among patients who experienced superimposed relapses during the course of secondary progressive disease, and patients with active secondary progressive multiple sclerosis who were receiving sustained immunotherapy were less likely to become wheelchair-dependent than those who were not receiving immunotherapy. Meaning The study's findings suggest that disease-modifying therapies are associated with a slower rate of disability accumulation in patients with active secondary progressive multiple sclerosis. This cohort study uses data from the MSBase international registry to examine the association of demographic and clinical factors, including the presence of relapses and exposure to immunotherapy, with the rate of disability accumulation in patients with secondary progressive multiple sclerosis. Importance It is unclear whether relapses and disease-modifying therapies are associated with the rate of disability accumulation in patients with secondary progressive multiple sclerosis (SPMS). Objective To examine the association of relapses with the rate of disability accumulation in patients with SPMS and to assess whether treatment before or during the secondary progressive phase can slow the progression of disability accumulation. Design, Setting, and Participants In this observational cohort study, patient data were prospectively collected from the MSBase international registry between January 1, 1995, and February 1, 2018. Among 53680 patients in the MSBase registry, 4997 patients with SPMS (using the Lorscheider definition) were identified. Of those, 1621 patients were eligible for study inclusion based on sufficient follow-up before and after the onset of SPMS. Data were analyzed from November 15, 2017, to January 13, 2020. Exposures The association between disability accumulation and several clinical and demographic variables, including relapses and exposure to immunotherapy, was evaluated. Main Outcomes and Measures Two outcomes were analyzed as measures of disability accumulation during SPMS: the rate of disability accumulation during the secondary progressive phase (change relative to the reference population of patients with MS and absolute change) and the risk of becoming wheelchair dependent. A third outcome, the cumulative risk of experiencing confirmed disability progression events, was used for a secondary analysis. Outcomes were evaluated using multivariable mixed models (ie, linear and Cox models). Results Of 1621 patients eligible for inclusion, 1103 patients (68.0%) were female, with a mean (SD) age at MS onset of 33.9 (10.6) years. A total of 661 patients (40.8%) experienced superimposed relapses during SPMS. Therapy receipt and relapses during early relapsing-remitting MS were not associated with disability accumulation during the secondary progressive phase. Higher relapse rates during the secondary progressive disease stage were associated with an increased risk of becoming wheelchair dependent (hazard ratio [HR], 1.87; 95% CI, 1.17-3.00; P = .009). Among patients who experienced superimposed relapses during SPMS, greater receipt of disease-modifying therapies was significantly associated with a reduced rate of disability progression and a lower risk of becoming wheelchair dependent. Conclusions and Relevance In this study, the rate of disability progression after the onset of SPMS was not associated with the early disease course and treatment decisions. Relapses during SPMS were associated with accelerated disability progression and represent an accessible treatment target. Disease-modifying therapy was associated with improvements in disability outcomes among patients with active relapses during SPMS. The study's results suggest that inflammatory disease activity remains a substantial yet modifiable component of SPMS.