Efficacy and safety of alemtuzumab versus fingolimod in RRMS after natalizumab cessation

J Neurol. 2019 Jan;266(1):165-173. doi: 10.1007/s00415-018-9117-z. Epub 2018 Nov 16.


Background: Natalizumab (NTZ) was the first approved monoclonal antibody for the treatment of relapsing-remitting multiple sclerosis (RRMS). Despite proven and sustained efficacy, its use is limited by the risk of progressive multifocal leukoencephalopathy (PML). Moreover, some patients show ongoing disease activity under NTZ, requiring a switch to another disease-modifying treatment (DMT). However, evidence regarding the optimal DMT for treatment of active RRMS after NTZ-cessation is still scarce.

Objective: To evaluate efficacy and safety outcomes of ALEM vs FTY treatment after cessation of NTZ.

Methods: We retrospectively identified patients at 12 German neurology centers and analyzed risks for disease activity, adverse events, disability progression, and treatment discontinuation.

Results: 195 patients were identified and 144 underwent final analysis (FTY: 101; ALEM: 42). The hazard ratio for clinical relapses was 2.24 favoring ALEM (95% CI 1.12-4.50; p = 0.015). The hazard ratio for adverse events was 7.78 (95% CI 1.04-57.95; p = 0.006) and 2.41 for MRI progression (95% CI 1.26-4.60; p = 0.004). The odds ratio for disability progression after 12 months was 4.84 (95% CI 1.74-13.47, p = 0.003). Differences remained after adjusting for possible confounders (e.g., age, sex, baseline disability, NTZ treatment duration, washout time).

Conclusion: Our findings indicated particular advantages of ALEM compared to FTY in patients stopping NTZ.

Keywords: Alemtuzumab; Fingolimod; Immunomodulatory therapy; Natalizumab; Progressive multifocal leukoencephalopathy; Remitting-relapsing multiple sclerosis.

Publication types

  • Comparative Study
  • Multicenter Study

MeSH terms

  • Adult
  • Alemtuzumab / adverse effects
  • Alemtuzumab / therapeutic use*
  • Disease Progression
  • Female
  • Fingolimod Hydrochloride / adverse effects
  • Fingolimod Hydrochloride / therapeutic use*
  • Humans
  • Immunologic Factors / adverse effects
  • Immunologic Factors / therapeutic use*
  • Immunomodulation
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / therapy*
  • Natalizumab / adverse effects
  • Natalizumab / therapeutic use*
  • Retrospective Studies
  • Treatment Outcome


  • Immunologic Factors
  • Natalizumab
  • Alemtuzumab
  • Fingolimod Hydrochloride