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Original Investigation
March 2018

Comparative Effectiveness of Rituximab and Other Initial Treatment Choices for Multiple Sclerosis

Author Affiliations
  • 1Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
  • 2Department of Pharmacology and Clinical Neuroscience, Section for Neurology, Umeå University, Umeå, Sweden
  • 3Department of Clinical Sciences Danderyds Hospital, Karolinska Institutet, Stockholm, Sweden
  • 4Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
JAMA Neurol. 2018;75(3):320-327. doi:10.1001/jamaneurol.2017.4011
Key Points

Question  How does traditional initial disease-modifying treatment choices compare with rituximab in relapsing-remitting multiple sclerosis regarding drug discontinuation and clinical efficacy?

Findings  In this cohort study that included a population-based sample of 494 patients from 2 Swedish counties, both drug survival and rate of sufficient treatment effect were significantly higher for rituximab compared with injectable disease-modifying treatments (interferons, glatiramer acetate), dimethyl fumarate, and, in most comparisons, fingolimod and natalizumab.

Meaning  Rituximab can be considered an option for treatment-naive patients with relapsing-remitting multiple sclerosis.


Importance  Comparative real-world effectiveness studies of initial disease-modifying treatment (DMT) choices for relapsing-remitting multiple sclerosis (RRMS) that include rituximab are lacking.

Objective  To assess the effectiveness and drug discontinuation rates of rituximab among patients with newly diagnosed RRMS compared with injectable DMTs, dimethyl fumarate, fingolimod, or natalizumab.

Design, Setting, and Patients  This retrospective cohort study used prospectively collected data to examine specialized care of 2 Swedish county–based community samples of patients with RRMS. Patients with RRMS who received diagnoses from January 1, 2012, to October 31, 2015, who resided in Stockholm or Västerbotten Counties were identified from a Swedish multiple sclerosis registry.

Main Outcomes and Measures  All reasons for drug discontinuation of initial treatment choice (main outcome) and specific reasons for switching (secondary outcomes) were analyzed with multivariable Cox regression, including propensity scores.

Results  Among 494 patients (median [interquartile range] age, 34.4 [27.4-43.4] years; 158 men [32.0%]), 215 received an injectable DMT (43.5%); 86 (17.4%), dimethyl fumarate; 17 (3.4%), fingolimod; 50 (10.1%), natalizumab; 120 (24.3%), rituximab; and 6 (1.2%), other DMT. Regional preferences were pronounced, with 42 of 52 (81%) and 78 of 442 (18%) receiving rituximab in Västerbotten and Stockholm, respectively. The annual discontinuation rate for rituximab, injectable DMTs, dimethyl fumarate, fingolimod, and natalizumab were 0.03, 0.53, 0.32, 0.38, and 0.29, respectively. Continued disease activity was the main reason for discontinuation of injectable DMTs, dimethyl fumarate, and fingolimod; positive John Cunningham virus serology results were the main reason for discontinuation of natalizumab. Rate of clinical relapses and/or neuroradiologic disease activity were significantly lower for rituximab compared with injectable DMTs and dimethyl fumarate, with a tendency for lower relapse rates also compared with natalizumab and fingolimod. The annual discontinuation rate of initial treatment choice was significantly lower in Västerbotten compared with Stockholm (0.09 and 0.37, respectively).

Conclusions and Relevance  Rituximab was superior to all other DMT in terms of drug discontinuation and displayed better clinical efficacy compared with injectable DMTs and dimethyl fumarate with borderline significance compared with natalizumab and fingolimod. The county where rituximab constituted the main initial treatment choice displayed better outcomes in most measured variables. Collectively, our findings suggest that rituximab performs better than other commonly used DMTs in patients with newly diagnosed RRMS.