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

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.

Natalizumab, rituximab and fingolimod as escalation therapy in multiple sclerosis

“…However, due to the limited number of patients in the treatment groups and a high and uneven percentage of patients lacking MRI data prior to baseline, it was not considered feasible to adjust the statistical comparisons for preswitch MRI data. The results of this study, implying similar efficacy for suppression of disease activity for NTZ and RTX, are in line with a previous study on treatment-naive patients with RRMS initiating a first DMT [7]. Our results are also in line with a previous study suggesting superior efficacy of RTX compared with FGL after switch from NTZ due to JCV positivity [8].…”

Blood neurofilament light levels segregate treatment effects in multiple sclerosis

“…4 The implementation of soluble but also novel imaging biomarkers that can complement current clinical and imaging monitoring likely will lead to an increased use of more effective DMTs and reduce the risks for patients to be exposed to insufficient treatment responses, in turn improving important long-term clinical outcomes. 12,29 We demonstrate that dynamics of pNfL are significantly influenced by specific DMTs and that the degree of pNfL reduction is correlated to clinical and patient-reported outcomes, but also that the baseline pNfL concentration exerts an unproportioned effect on on-treatment values in the medium term. In order to understand if pNfL can be used as a drug response biomarker at the individual level, further studies are needed to address the correlation of pNfL changes to long-term clinical outcomes with different DMTs, as well as if modeling of pNfL dynamics can be improved further by including additional variables such as MRI data or more frequent measurements.…”

Enforced microglial depletion and repopulation as a promising strategy for the treatment of neurological disorders

“…Taking MS for example, monoclonal antibodies (including Rituximab and Ocrelizumab) that selectively target and deplete CD20 + B cells have been approved for the treatment of MS (Greenfield & Hauser, ; Hauser et al, ; Sabatino, Zamvil, & Hauser, ; Salzer et al, ). Our colleagues have demonstrated that relapsing–remitting MS patients with Rituximab as the initial treatment have better relapse control and tolerability in comparison with other disease‐modifying drugs (Granqvist et al, ; Spelman, Frisell, Piehl, & Hillert, ). Available MS treatments mainly resolve the peripheral inflammation but further specific and effective cell‐depletion therapies still represent a highly unmet medical need, especially in chronic disease states.…”