Thyroid autoimmunity following alemtuzumab treatment in multiple sclerosis patients: a prospective study

Autoimmune thyroid disease (AITD) is the most common adverse effect in alemtuzumab (ALZ) treated relapsing-remitting (RR) multiple sclerosis (MS) patients. The objective of this prospective study was to analyze the occurrence, timing of onset, clinical course, and laboratory characteristics of AITD post-ALZ. We evaluated 35 RRMS patients treated with ALZ at a single academic MS center; clinical and laboratory data were collected before ALZ initiation and thereafter quarterly on follow-up with a median of 43.5 months. Seventeen out of 31 patients (54.8%) with no prior history of thyroid dysfunction developed AITD with a mean onset of 19.4 months ± 10.2 (SD) after the first ALZ cycle; Graves' disease (GD) (n = 9); hypothyroidism with positive stimulating thyrotropin receptor antibodies (TRAb) (n = 1); Hashimoto thyroiditis (HT) (n = 6); HT with hypothyroidism (n = 1). Interestingly, seven of nine (77.7%) GD patients showed a fluctuating course. Three out of four patients with preexisting thyroid disease remained stable, whereas one with prior HT and hypothyroidism developed fluctuating GD. All patients with GD commenced antithyroid drugs (ATDs); five continued on "block and replace" treatment; one required radioactive iodine, and one total thyroidectomy. Our analysis showed earlier onset of ALZ-induced AITD in comparison to most other ALZ cohorts; overall, these patients required complex therapeutic approaches of the AITD. We observed a higher rate of fluctuating GD, with earlier onset and lower remission rate than previously reported, which in the majority of patients required prolonged "block and replace" therapy in the minimum dose of each therapeutic agent or more definitive interventions.