Alemtuzumab as rescue therapy in a cohort of 50 relapsing-remitting MS patients with breakthrough disease on fingolimod: a multi-center observational study

J Neurol. 2018 Jul;265(7):1521-1527. doi: 10.1007/s00415-018-8871-2. Epub 2018 Apr 25.

Abstract

Background: Relapsing-remitting multiple sclerosis (RRMS) requires efficient immunomodulatory treatment to reach "no evidence of disease activity" status at best. Alemtuzumab and fingolimod have proved to be efficient options in RRMS with active disease course. Yet, side effects and break-through disease may limit long-time treatment and necessitate switch of medication. Data on efficacy and safety of alemtuzumab following fingolimod treatment are limited, but useful for clinical practice.

Methods: Clinical and MRI data of 50 RRMS patients with a history of therapy switch from fingolimod to alemtuzumab were retrospectively analyzed. Data were acquired from nine large German MS Centers from 2013 to 2016 and analyzed using descriptive statistics.

Results: On average, patients with disease duration of 12.9 years and median EDSS of 3.0 at baseline switched to alemtuzumab after 68 weeks of fingolimod treatment. Thereafter, patients on alemtuzumab were followed for a mean of 64 weeks. The annualized relapse rate decreased from 2.2 in the year prior to 0.34 in the following year after switching to alemtuzumab and EDSS stabilized. In a subgroup of patients (n = 23), MRI data point to a reduction in enhancing (4.47 vs. 0.26) and new/enlarging T2 lesions (5.8 vs. 0.27) after treatment adjustment. Side effects were generally as expected from published data for alemtuzumab (autoimmunity 2/50, severe infections 1/50). One patient suffered combined lethal necrotizing leukoencephalopathy and hemolytic anemia.

Discussion: Therapy switch was highly effective in reducing clinical and MRI surrogates of disease activity and was mainly well tolerated within one year of follow-up. Hence, alemtuzumab constitutes a promising therapy in RRMS with refractory disease activity despite fingolimod treatment. Further studies are warranted to confirm these beneficial findings and to reveal safety concerns in the longer-term follow-up.

Keywords: Alemtuzumab; Disease-modifying treatment; Fingolimod; Multiple sclerosis.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Adult
  • Alemtuzumab / therapeutic use*
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Cohort Studies
  • Disability Evaluation
  • Female
  • Fingolimod Hydrochloride / therapeutic use*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Lymphocytes / drug effects
  • Lymphocytes / pathology
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / diagnostic imaging
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Young Adult

Substances

  • Antineoplastic Agents, Immunological
  • Immunosuppressive Agents
  • Alemtuzumab
  • Fingolimod Hydrochloride