Alemtuzumab induces severe orbitopathy in relapsing-remitting multiple sclerosis

J Neurol. 2024 Jan;271(1):486-496. doi: 10.1007/s00415-023-11995-6. Epub 2023 Sep 29.

Abstract

Context: Treatment with Alemtuzumab (ALZ) in patients with Relapsing-Remitting Multiple Sclerosis (RRMS) is associated with the development of ALZ-induced Graves' disease (GD-ALZ). Some cases may develop associated Graves´ Orbitopathy (GO-ALZ), with possible visual compromise.

Aim: The aim of this study was to describe the main clinical and biochemical characteristics of GD-ALZ, as well as the clinical course of a case series of GO-ALZ METHODS: This study is a retrospective observational study, carried out in a reference hospital for the care of patients with RRMS in Spain. Cases treated with ALZ in the period 2014-2022 were included. GO-ALZ cases were identified among those with clinical symptoms compatible with thyroid eye disease after initiating ALZ treatment.

Results: A total of 135 cases, with a mean follow-up of 69.6 months after the first ALZ cycle, were included. The incidence of GD-ALZ was 32.6% (44/135), with a predominance of women (77.3%) and mean age of 41.9 years. The presence of first-degree relatives with hypothyroidism was identified as risk factor for the development of GD-ALZ (adjusted P-value: 0.02). GO-ALZ was diagnosed in 6 cases (incidence: 13.6%), of which 3 had severe clinical forms of GO, requiring anti-IL-6 treatment. A favorable response was reported in all of them, with a significant decrease in disease activity and improvement in proptosis.

Conclusions: We report one of the largest cohorts of GD-ALZ and GO-ALZ cases. The diagnosis of these entities should be taken into account in patients treated with Alemtuzumab, given the risk of developing severe clinical forms. In moderate-severe forms of GO-ALZ, drugs with anti-IL-6 activity are a safe and effective option.

Keywords: Alemtuzumab; Graves’ orbitopathy; Hyperthyroidism; Relapsing–remitting multiple sclerosis; Tocilizumab.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Alemtuzumab / adverse effects
  • Female
  • Graves Disease* / complications
  • Graves Disease* / diagnosis
  • Graves Disease* / epidemiology
  • Graves Ophthalmopathy* / chemically induced
  • Graves Ophthalmopathy* / drug therapy
  • Graves Ophthalmopathy* / epidemiology
  • Humans
  • Male
  • Multiple Sclerosis* / complications
  • Multiple Sclerosis, Relapsing-Remitting* / complications

Substances

  • Alemtuzumab