Rituximab in Multiple Sclerosis: Better Efficacy, Lower Discontinuation Rates Than Other Treatments

Rituximab (Rituxan) is more effective and has lower rates of discontinuation than other disease-modifying treatments in newly diagnosed patients with relapsing-remitting multiple sclerosis (RRMS), according to a Swedish study published online in the January 8, 2018, issue of JAMA Neurology.

Researchers, led by Mathias Granqvist, MD, compared rituximab to the injectable DMTs dimethyl fumarate (Tecfidera), fingolimod (Gilenya), and natalizumab (Tysabri), and concluded that rituximab can be considered an option for treatment-naïve patients with RRMS. "Collectively, our findings suggest that rituximab performs better than other commonly used DMTs in patients with newly diagnosed RRMS," they said.

In Sweden, all DMTs are covered by national health insurance, including use in off-label indications (rituximab—innovator or EU-approved biosimilar—is not approved for the treatment of RRMS).

Real-world data show high rates of drug discontinuation among patients with RRMS who receive traditional first-line treatments—injectable DMTs interferon beta (Avonex, Rebif) and glatiramer acetate (Copaxone, Glatopa)—with fewer than half of patients remaining on therapy after 2 years.

Off-label use of rituximab in MS patients has increased in Sweden, but differs strongly by region. The researchers used this regional difference to compare outcomes for patients with RRMS who were receiving their first DMT in a region using a traditional escalating strategy (Stockholm County) with a region using a sustained induction strategy, initiating and maintaining treatment with highly efficient therapies (Västerbotten County, where rituximab was predominantly used). The study compared outcomes for rituximab with all other frequently used DMTs in the combined cohort.

The trial included 494 patients identified from a registry of all patients in Stockholm and Västerbotten Counties diagnosed with RRMS and started on a DMT from January 1, 2012, to October 31, 2015. A total of 43.5% received an injectable DMT; 17.4% received dimethyl fumarate, 3.4% fingolimod, 10.1% natalizumab, 24.3% rituximab, and 1.2% other DMTs.

There were pronounced regional differences in treatment, with 81% and 18% of patients in Västerbotten and Stockholm Counties, respectively, receiving rituximab. The annual discontinuation rates were 0.03, 0.53, 0.32, 0.38, and 0.29 for rituximab, injectable DMTs, dimethyl fumarate, fingolimod, and natalizumab, respectively. Continued disease activity was the main reason cited for discontinuation of injectable DMTs, dimethyl fumarate, and fingolimod. The main reason for discontinuation of natalizumab was positive John Cunningham virus serology results.

The rate of clinical relapses and/or neuroloradiologic disease activity were significantly lower in patients receiving rituximab compared with patients receiving injectable DMTs and dimethyl fumarate, with a tendency for lower relapse rates compared with natalizumab and fingolimod. The annual discontinuation rate of initial treatment choice was significantly lower in Västerbotten County compared with Stockholm County (0.09 and 0.37, respectively).

Rituximab was superior to all other DMTs in terms of drug discontinuation rate, and showed better clinical efficacy compared with injectable DMTs and dimethyl fumarate, with borderline significance compared with natalizumab and fingolimod. The county in which rituximab constituted the main initial treatment choice showed better outcomes in most measured variables. Milder adverse events (AEs) were more frequent with injectable DMTs compared with rituximab, whereas moderate to severe AEs were similarly low. AEs did not differ significantly between rituximab, fingolimod, and natalizumab.

The researchers note that the argument for starting with less effective DMTs concerns mainly safety and price. Newer and more effective DMTs have been associated with risks of serious AEs and usually command a substantially higher price than platform therapies, they say, and documentation of the safety profile of natalizumab and fingolimod in patients with MS is more extensive than for rituximab. Thus, although there is extensive experience of long-term use of rituximab in patients with rheumatoid arthritis, with a good tolerability profile and a low risk of malignancies, extrapolation to MS should be made with caution due to differences in patient populations and dose and administration regimens.

With respect to price, however, rituximab used at a single dose of 500 mg or 1000 mg twice yearly results in lower treatment costs than even platform therapies, but the status of being an off-label drug, and therefore subject to variable insurance regulations in countries other than Sweden, remains as a barrier for the use of rituximab in patients with MS.