Comparison of the Response to Rituximab between Myelin Oligodendrocyte Glycoprotein and Aquaporin-4 Antibody Diseases

Ann Neurol. 2020 Feb;87(2):256-266. doi: 10.1002/ana.25648. Epub 2019 Nov 27.

Abstract

Objective: To compare response to rituximab (RTX) between adult patients positive for myelin oligodendrocyte glycoprotein (MOG) and aquaporin-4 (AQP4) antibodies.

Methods: We prospectively studied adult patients with MOG or AQP4 antibodies who received RTX under an individualized dosing schedule adapted to the biological effect of RTX monitored by memory B-cell measurement. Memory B cells were counted monthly and when relapse occurred. The biological effect of RTX was considered significant with <0.05% memory B cells in peripheral blood lymphocytes.

Results: In 16 patients with MOG antibodies and 29 with AQP4 antibodies, mean follow-up was 19 (range = 9-38) and 38 (13-79) months. Under RTX, 10 relapses occurred in 6 of 16 (37.5%) patients with MOG antibodies, and 13 occurred in 7 of 29 (24%) with AQP4 antibodies. The median time of relapse after the most recent infusion was 2.6 (0.6-5.8) and 7 (0.8-13) months, respectively (p < 0.001). Memory B cells had reemerged in 2 of 10 (20%) relapses in patients with MOG antibodies and 12 of 13 (92.5%) with AQP4 antibodies (p < 0.001).

Interpretation: In AQP4 antibody-associated disorder, relapse mostly occurs when the biological effect of RTX decreases, which argues for treatment efficacy. In MOG antibody-associated disorder, the efficacy of RTX is not constant, because one-third of patients showed relapse despite an effective biological effect of RTX. In this subpopulation, memory B-cell depletion was unable to prevent relapse, which was probably caused by different immunological mechanisms. These findings should be used to improve treatment strategies for MOG antibody-associated disorder. ANN NEUROL 2020;87:256-266.

Publication types

  • Comparative Study
  • Observational Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aquaporin 4 / immunology*
  • Autoantibodies / blood
  • B-Lymphocyte Subsets / drug effects
  • Cell Count
  • Demyelinating Diseases / blood
  • Demyelinating Diseases / drug therapy*
  • Demyelinating Diseases / immunology
  • Female
  • Humans
  • Immunologic Factors / therapeutic use
  • Male
  • Middle Aged
  • Myelin-Oligodendrocyte Glycoprotein / immunology*
  • Rituximab / therapeutic use*
  • Treatment Outcome
  • Young Adult

Substances

  • Aquaporin 4
  • Autoantibodies
  • Immunologic Factors
  • Myelin-Oligodendrocyte Glycoprotein
  • Rituximab