Compassionate open-label use of rituximab following a randomised clinical trial against neuromyelitis optica (RIN-2 study): B cell monitoring-based administration

Mult Scler Relat Disord. 2022 Apr:60:103730. doi: 10.1016/j.msard.2022.103730. Epub 2022 Mar 7.

Abstract

Objective: The aim of the RIN-2 study was a compassionate use of rituximab (RTX) for patients who completed the RIN-1 study, a multicentre, randomised, double-blind, placebo-controlled trial of RTX. We also investigated the long-term safety and efficacy of RTX.

Methods: A study design was a prospective open-label extension study following the RIN-1 study. RTX was infused repeatedly under monthly monitoring of CD19-positive and CD 20-positive B cell lymphocyte subsets from 24 weeks after an infusion.

Results: Thirty-three (87%) of 38 patients of the RIN-1 study were enrolled from February 2016 to March 2019 at six sites in Japan. In RIN-2, RTX was administered three times (median, range 1-5 times), and the interval of RTX administrations were 9.5 [2.5] months (mean [SD]). The observation period was 20.5 [10.1] months. During the trial, three patients dropped out due to two withdrawals and one adverse event. During the study, 28 (90%) of 31 patients were treated with RTX monotherapy. Neuromyelitis optica (NMO) relapses were observed in two patients. The annualized relapse rate (ARR) was 0.035 counts per person-years, ∼1/10th compared with 0.321 in the placebo arm of the RIN-1 study. We observed 14 severe adverse events in six (18%) and 156 adverse events, of which 135 were grade 1, 11 were grade 2 and 10 were grade 3.

Conclusions: Under B cell monitoring, the interval of RTX re-infusion was elongated to nine months, and NMO relapses were suppressed with 0.035 of ARR.

Keywords: Aquaporin 4; Clinical trial; Neuromyelitis optica spectrum disorders; Open-label; Rituximab.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Compassionate Use Trials
  • Humans
  • Immunologic Factors / therapeutic use
  • Neoplasm Recurrence, Local / drug therapy
  • Neuromyelitis Optica* / chemically induced
  • Neuromyelitis Optica* / drug therapy
  • Prospective Studies
  • Rituximab / adverse effects
  • Treatment Outcome

Substances

  • Immunologic Factors
  • Rituximab