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Original Investigation
January 7, 2019

Association of Rituximab Treatment With Disability Progression Among Patients With Secondary Progressive Multiple Sclerosis

Author Affiliations
  • 1Neurologic Clinic and Policlinic, University Hospital and University of Basel, Basel, Switzerland
  • 2Clinical Trial Unit, Department of Clinical Research, University of Basel, University Hospital Basel, Basel, Switzerland
  • 3MS Center Amsterdam, Department of Neurology, VU University Medical Center, Amsterdam, the Netherlands
  • 4Multiple Sclerosis Center, Neurocenter of Southern Switzerland, Ospedale Regionale di Lugano, Lugano, Switzerland
JAMA Neurol. 2019;76(3):274-281. doi:10.1001/jamaneurol.2018.4239
Key Points

Question  Does disability progression among patients with secondary progressive multiple sclerosis treated with the monoclonal anti-CD20 antibody rituximab differ from that among such patients never treated with rituximab?

Findings  In this cohort study of 88 propensity score–matched patients, those treated with rituximab had a significantly lower Expanded Disability Status Scale score for up to 10 years of follow-up and significantly delayed confirmed progression compared with matched controls. No associations between confirmed progression and individual patient baseline characteristics were identified.

Meaning  Therapeutic options for patients with secondary progressive multiple sclerosis are limited; however, these findings suggest that B-cell–depleting therapy may be beneficial.

Abstract

Importance  Therapeutic options for patients with secondary progressive multiple sclerosis (SPMS) are limited.

Objective  To analyze disability progression in patients with SPMS treated with rituximab compared with matched control patients never treated with rituximab.

Design, Setting, and Participants  This retrospective cohort study analyzed data obtained from patients with SPMS at 3 multiple sclerosis centers located in Basel and Lugano, Switzerland, and Amsterdam, the Netherlands, from 2004 to 2017. Patients were included for analysis if they had received a diagnosis of SPMS, were treated (57 eligible; 54 included) or never treated (504 eligible; 59 included) with rituximab, and had at least 1 follow-up visit. The variables used for propensity score matching were sex, age, Expanded Disability Status Scale (EDSS) score, and disease duration. Follow-up duration was up to 10 years, with a mean (SD) of 3.5 (2.6) years for rituximab-treated patients and 5.4 (2.4) years for controls in the total cohort and a mean (SD) of 3.5 (2.7) years for rituximab-treated patients and 4.8 (2.2) years for controls in the matched cohort.

Exposures  Comparing EDSS score progression in patients with SPMS (treated with rituximab vs not treated with rituximab) using propensity score matching.

Main Outcomes and Measures  The primary end point was progression of EDSS score after baseline, and the secondary end point was time to confirmed disability progression.

Results  After 1:1 propensity score matching, 44 matched pairs (88 patients) were included in the analysis. At baseline, patients treated with rituximab had a mean (SD) age of 49.7 (10.0) years, mean (SD) disease duration of 18.2 (9.4) years, and mean (SD) EDSS score of 5.9 (1.4), and 26 (59%) were women, whereas controls had a mean (SD) age of 51.3 (7.4) years, mean (SD) disease duration of 19.4 (8.7) years, and mean (SD) EDSS score of 5.70 (1.29), and 27 (61%) were women. In the covariate-adjusted analysis of the matched set, patients with SPMS who were treated with rituximab had a significantly lower EDSS score during a mean (SD) follow-up of 3.5 (2.7) years (mean difference, −0.52; 95% CI, −0.79 to −0.26; P < .001). Time to confirmed disability progression was significantly delayed in the rituximab-treated group (hazard ratio, 0.49; 95% CI, 0.26-0.93; P = .03).

Conclusions and Relevance  In this study, patients with SPMS treated with rituximab had a significantly lower EDSS score for up to 10 years of follow-up and a significantly delayed confirmed progression compared with matched controls, suggesting that B-cell depletion by rituximab may be therapeutically beneficial in these patients. A prospective randomized clinical trial with a better level of evidence is needed to confirm the efficacy of rituximab in such patients.

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