Repeated treatment with rituximab based on the assessment of peripheral circulating memory B cells in patients with relapsing neuromyelitis optica over 2 years

Arch Neurol. 2011 Nov;68(11):1412-20. doi: 10.1001/archneurol.2011.154. Epub 2011 Jul 11.

Abstract

Objective: To evaluate the efficacy and safety of repeated rituximab treatment based on the assessment of peripheral circulating memory B cells over 24 months in patients with relapsing neuromyelitis optica (NMO).

Design: Prospective open-label study.

Setting: Institutional referral center for multiple sclerosis. Patients Thirty patients with relapsing NMO or NMO spectrum disorder. Intervention Treatment protocol of rituximab consisted of an induction therapy (375 mg/m² once weekly for 4 weeks or 1000 mg infused twice, with a 2-week interval between the infusions) followed by maintenance therapy. The maintenance therapy was repeated treatment with rituximab (375 mg/m², once) whenever the frequency of reemerging CD27+ memory B cells was more than 0.05% in peripheral blood mononuclear cells by flow cytometric analysis.

Main outcome measures: Annualized relapse rate, disability (Expanded Disability Status Scale score), anti-aquaporin 4 antibody level, and safety of rituximab treatment.

Results: Of 30 patients, 28 showed a marked reduction in relapse rate while taking rituximab over 24 months. The relapse rate was reduced significantly, by 88%, and 70% of patients became relapse-free over 24 months. Disability either improved or stabilized in 97% of patients. Anti-aquaporin 4 antibody levels declined significantly following treatment with rituximab, consistent with the clinical response and the effect on CD27+ memory B cells. Repeated treatment with rituximab was generally well tolerated, and no clinically relevant adverse event leading to discontinuation of treatment was observed.

Conclusion: Repeated treatment with rituximab appeared to produce consistent and sustained efficacy over 24 months with good tolerability in patients with NMO.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Monoclonal, Murine-Derived / administration & dosage*
  • B-Lymphocyte Subsets / drug effects
  • B-Lymphocyte Subsets / metabolism*
  • Drug Administration Schedule
  • Female
  • Humans
  • Immunologic Memory / drug effects
  • Immunologic Memory / physiology*
  • Male
  • Middle Aged
  • Neuromyelitis Optica / blood*
  • Neuromyelitis Optica / drug therapy*
  • Neuromyelitis Optica / immunology
  • Prospective Studies
  • Rituximab
  • Secondary Prevention
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Rituximab