Ocrelizumab in MS patients with persistence of disease activity after alemtuzumab: A multi-center Italian study

Mult Scler. 2024 Aug;30(9):1151-1162. doi: 10.1177/13524585241266509. Epub 2024 Aug 14.

Abstract

Background: The reason why some multiple sclerosis (MS) patients show disease activity after alemtuzumab (ALM) is still unclear, but ocrelizumab (OCR) could represent an interesting sequential therapeutic approach.

Objectives: To investigate safety and efficacy of OCR in MS patients with disease activity after two ALM courses.

Methods: Observational retrospective multi-centers Italian cohort study.

Results: Seventy-two subjects were included. Mean follow-up (FU) was 2.4 (±1) years. Forty-five patients (62.5%) experienced at least one adverse event (AE), with infections accounting for 96.7% of cases. A reduction in total lymphocytes was observed between OCR start and 6 months FU, driven by BCD19+ lymphocytes depletion (p < 0.001). Immunoglobulin M (IgM) levels decreased between OCR start and 6 months FU (p < 0.001). At 2-year FU, relapse, magnetic resonance imaging (MRI) activity and disability worsening-free survival were 92.1%, 90.8%, and 89.2%. The evidence of inflammatory activity between the two ALM courses was associated with higher risk of relapse, MRI activity, and NEDA-3 status loss in relapsing-remitting multiple sclerosis (RRMS; p = 0.02, p = 0.05, p = 0.01, respectively).

Conclusions: OCR after two ALM courses seemed to be safe and effective. Early IgM hypogammaglobulinemia occurred in a high proportion of patients. The evidence of inflammatory activity between ALM courses seemed to increase the risk of MS re-activation on OCR treatment.

Keywords: Multiple sclerosis; alemtuzumab; efficacy; induction; ocrelizumab; safety; therapy.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Adult
  • Alemtuzumab* / adverse effects
  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Female
  • Follow-Up Studies
  • Humans
  • Immunologic Factors* / adverse effects
  • Italy
  • Male
  • Middle Aged
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy
  • Retrospective Studies

Substances

  • Antibodies, Monoclonal, Humanized
  • Alemtuzumab
  • Immunologic Factors
  • ocrelizumab