Studies Report on Efforts to Optimize Rituximab in MS, NMOSD

While rituximab does not carry indications for the treatment of multiple sclerosis (MS) or aquaporin-4-positive (AQP4) neuromyelitis optica spectrum disorder (NMOSD), the CD20-depleting therapy and its biosimilars are commonly used off-label, as the therapy has been demonstrated to be effective in reducing relapses in MS as well as in reducing the frequency and severity of attacks in NMOSD.

The availability of biosimilar rituximab—already a reality in Europe and soon to arrive in the United States—has the potential to increase patient access to anti-CD20 therapy, but despite the common use of the drug in neurology, there are few data that help guide individual patients’ treatment with rituximab. Important questions remain, such as how long a patient should ideally be treated with rituximab, on what schedule treatment should occur, or what therapies may be optimal after treatment with the product is discontinued.

During last week’s 35th Annual Congress of the European Committee for Treatment and Research in Multiple Sclerosis, which was held in Stockholm, Sweden, multiple teams presented findings on the use of rituximab in both of these challenging neurological disorders.

First, in a poster session, researchers from the Institute of Neuropathology and University Medical Center Göttingen, in Göttingen, Germany, presented findings on their study on the phenotype and function of B cells that reappear after treatment with rituximab.¹

The researchers assessed peripheral blood mononuclear cells of 15 patients with relapsing MS prior to rituximab therapy and during B-cell repletion. They found that, while most B cells before rituximab treatment were mature memory B cells, the B cells that reappeared showed a naïve phenotype, and also manifested an accentuated activation profile and a more proinflammatory cytokine profile.

These findings suggest the need for further exploration of the phenotype of these repleting B cells to help guide therapeutic decisions, particularly with regard to maintenance therapies that may be initiated after treatment with anti-CD20 agents like rituximab.

Additionally, researchers from Marseille University Hospital, in Marseille, France, presented their findings from a study of 2 different individualized administration schedules for treating patients with aquaporin-4-positive neuromyelitis optica spectrum disorder (NMOSD) using rituximab.²

In the study, 15 patients with NMOSD were treated using a standard approach, under which rituximab is readministered only once memory B cells reached 0.05% of peripheral blood mononuclear cells, and 29 patients were treated with an optimized scheme under which patients were retreated at 6 months, or before 6 months if their B cells had repleted to the 0.05% threshold. The investigators then compared annual relapse rates for the 2 groups.

They found that, among patients treated with the standard approach, the mean annual relapse rate was 0.35 (range, 0-1.6). Among the patients who were treated with the optimized approach, the mean annual relapse rate was 0.04 (range, 0-0.7).

According to the study’s authors, the optimized treatment schedule reduces the risk of relapse after 6 months, a risk inherent to the standard treatment approach.

References

1. Nissimov N, Hajiyeva Z, Brück W, Häusser-Kinzel S, Weber MS. Phenotype of repleting B cells in multiple sclerosis patients treated with rituximab. Presented at: The 35th Congress of the European Society for Treatment and Research in Multiple Sclerosis; September 11-13, 2019; Stockholm, Sweden. Poster P1389.

2. Durozard P, Rico A, Boutiere C, et al. Comparison of two individualized administration schemes of rituximab based on memory B cells monitoring in AQP4 positive disorder. Presented at: The 35th Congress of the European Society for Treatment and Research in Multiple Sclerosis; September 11-13, 2019; Stockholm, Sweden. Abstract P1352.