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Comparative Effectiveness of Rituximab and Other Initial Treatment Choices for Multiple Sclerosis.
JAMA Neurol. 2018 03 01; 75(3):320-327.JN

Abstract

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.

Authors+Show Affiliations

Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.Department of Pharmacology and Clinical Neuroscience, Section for Neurology, Umeå University, Umeå, Sweden.Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.Department of Clinical Sciences Danderyds Hospital, Karolinska Institutet, Stockholm, Sweden.Department of Pharmacology and Clinical Neuroscience, Section for Neurology, Umeå University, Umeå, Sweden.Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29309484

Citation

Granqvist, Mathias, et al. "Comparative Effectiveness of Rituximab and Other Initial Treatment Choices for Multiple Sclerosis." JAMA Neurology, vol. 75, no. 3, 2018, pp. 320-327.
Granqvist M, Boremalm M, Poorghobad A, et al. Comparative Effectiveness of Rituximab and Other Initial Treatment Choices for Multiple Sclerosis. JAMA Neurol. 2018;75(3):320-327.
Granqvist, M., Boremalm, M., Poorghobad, A., Svenningsson, A., Salzer, J., Frisell, T., & Piehl, F. (2018). Comparative Effectiveness of Rituximab and Other Initial Treatment Choices for Multiple Sclerosis. JAMA Neurology, 75(3), 320-327. https://doi.org/10.1001/jamaneurol.2017.4011
Granqvist M, et al. Comparative Effectiveness of Rituximab and Other Initial Treatment Choices for Multiple Sclerosis. JAMA Neurol. 2018 03 1;75(3):320-327. PubMed PMID: 29309484.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative Effectiveness of Rituximab and Other Initial Treatment Choices for Multiple Sclerosis. AU - Granqvist,Mathias, AU - Boremalm,Malin, AU - Poorghobad,Amyar, AU - Svenningsson,Anders, AU - Salzer,Jonatan, AU - Frisell,Thomas, AU - Piehl,Fredrik, PY - 2018/1/9/pubmed PY - 2019/9/10/medline PY - 2018/1/9/entrez SP - 320 EP - 327 JF - JAMA neurology JO - JAMA Neurol VL - 75 IS - 3 N2 - 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. SN - 2168-6157 UR - https://www.unboundmedicine.com/medline/citation/29309484/Comparative_Effectiveness_of_Rituximab_and_Other_Initial_Treatment_Choices_for_Multiple_Sclerosis_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/jamaneurol.2017.4011 DB - PRIME DP - Unbound Medicine ER -