Association of Rituximab Treatment With Disability Progression Among Patients With Secondary Progressive Multiple Sclerosis
Authors: Yvonne Naegelin, Peter Naegelin, Stefanie von Felten, Johannes Lorscheider, Judith Sonder, Bernard M. J. Uitdehaag, Barbara Scotti, Chiara Zecca, Claudio Gobbi, Ludwig Kappos, Tobias Derfuss
Journal: JAMA Neurology (2019)

<h3>Importance</h3> Therapeutic options for patients with secondary progressive multiple sclerosis (SPMS) are limited. <h3>Objective</h3> To analyze disability progression in patients with SPMS treated with rituximab compared with matched control patients never treated with rituximab. <h3>Design, Setting, and Participants</h3> 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. <h3>Exposures</h3> Comparing EDSS score progression in patients with SPMS (treated with rituximab vs not treated with rituximab) using propensity score matching. <h3>Main Outcomes and Measures</h3> The primary end point was progression of EDSS score after baseline, and the secondary end point was time to confirmed disability progression. <h3>Results</h3> 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;<i>P</i> &lt; .001). Time to confirmed disability progression was significantly delayed in the rituximab-treated group (hazard ratio, 0.49; 95% CI, 0.26-0.93;<i>P</i> = .03). <h3>Conclusions and Relevance</h3> 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.