Alemtuzumab-induced thyroid disease: A Danish cohort study

Objectives: Alemtuzumab, a monoclonal antibody against the cluster of differentiation 52 (CD52) molecule, is used in the treatment of multiple sclerosis (MS). A side effect of the treatment is development of secondary autoimmune thyroid disease. The aim of this study was to evaluate the rate, type and course of thyroid disease in Danish patients with multiple sclerosis (MS) treated with alemtuzumab. Methods: We conducted a retrospective cohort study of patients treated with a first series of alemtuzumab for MS in the Capital and Zealand regions of Denmark (population: 2.6 million) between 2014 and 2018 (n = 60 Results: The duration of follow-up was median 81 months (range 54-105). Thyroid disease occurred in 47 % of the patients with the following distribution: Graves' disease (GD), thyrotropin (TSH) receptor antibody (TRAb) positive hyper- or hypothyroidism 35 %; multinodular goitre 5 %; silent thyroiditis, gestational transient thyrotoxicosis or unclassified hyperthyroidism 7 %. Of patients with GD, 14 % had an additional silent or postpartum thyroiditis before onset or after remission of GD. Unusual courses of GD occurred in 67 %, most commonly fluctuation from hypo- to hyperthyroidism or vice versa, mainly treated with antithyroid drug alone or thyroxine substitution regime but switched to concomitant block and replace treatment in 25 % and/or subsequent total thyroidectomy in less than 25 %. Conclusion: Data from the largest Danish MS center supports previous observations of unusual, long-lasting and unpredictable courses of alemtuzumab-induced GD. Thus, follow-up of these patients may require long lasting and more frequent biochemical measurements compared to other patients with GD. Also, concomitant block and replace treatment or definitive treatment, such as thyroidectomy, should be considered in a subgroup of patients.