Alemtuzumab-induced thyroid events in multiple sclerosis: a systematic review and meta-analysis

J Endocrinol Invest. 2020 Feb;43(2):219-229. doi: 10.1007/s40618-019-01105-7. Epub 2019 Aug 26.

Abstract

Purpose: Autoimmune thyroid events (ATEs) are common side effects after alemtuzumab (ALZ) therapy in patients with multiple sclerosis (MS). Our purpose was to reach more robust evidence on prevalence and outcome of the spectrum of alemtuzumab-induced autoimmune thyroid events in patients with multiple sclerosis.

Methods: PubMed and Scopus were systematically searched through July 2019. Studies dealing with patients without personal history of thyroid dysfunctions and affected by MS treated with ALZ and reporting ATEs were selected. Data on prevalence and outcome of ATEs were extracted. A proportion of meta-analysis with random-effects model was performed.

Results: Considering the overall pooled number of 1362 MS patients treated with ALZ (seven included studies), a 33% prevalence of newly diagnosed ATEs was recorded. Among all ATEs, Graves' disease (GD) was the most represented [63% of cases, 95% confidence interval (CI) 52-74%], followed by Hashimoto thyroiditis (15%, 95% CI 10-22%). Interestingly, GD showed a fluctuating course in 15% of cases (95% CI 8-25%). Of all GD, 12% (95% CI 2-42%) likely had spontaneous remission, 56% (95% CI 34-76%) required only antithyroid drugs, 22% (95% CI 13-32%) needed additional RAI, and 11% (95% CI 0.9-29%) underwent definitive surgery.

Conclusion: Among different categories of ATEs, Graves' hyperthyroidism was the most common thyroid dysfunction, occurring in more than half of cases. Antithyroid drugs should represent the first-line treatment for ALZ-induced GD patients. However, alemtuzumab-induced GD could not be considered as having a more favourable outcome than conventional GD, given the substantial chance to encounter a fluctuating and unpredictable course.

Keywords: Alemtuzumab; Multiple sclerosis; Side effects; Thyroid.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Alemtuzumab / adverse effects*
  • Antineoplastic Agents, Immunological / adverse effects*
  • Antithyroid Agents / therapeutic use
  • Humans
  • Multiple Sclerosis / diagnosis
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / immunology
  • Observational Studies as Topic / methods
  • Randomized Controlled Trials as Topic / methods
  • Thyroid Diseases / chemically induced*
  • Thyroid Diseases / diagnosis
  • Thyroid Diseases / immunology

Substances

  • Antineoplastic Agents, Immunological
  • Antithyroid Agents
  • Alemtuzumab