Pretreatment anti-thyroid autoantibodies indicate increased risk for thyroid autoimmunity secondary to alemtuzumab: A prospective cohort study

Background: Alemtuzumab is approved for the treatment of active relapsing-remitting multiple sderosis (RRMS). Alemtuzumab-related secondary autoimmune disorders (sAID) are common, with thyroid sAID being the most frequent, and fundamentally affect the risk-benefit ratio. Therefore, biomarkers indicating the development of sAID are urgently needed to instruct clinical decisions. Methods: We evaluated whether the anti-thyroid autoantibodies (ThyAb) anti-thyroglobul in (anti-TG) and antithyroid-peroxidase (anti-TPO) detected at baseline by standard testing are able to indicate increased risk for thyroid SAID following alemtuzumab treatment in a multicentre prospective cohort of 106 alemtuzumab-treated RRMS patients. We here present an interim-analysis with a median follow-up of 36 months. Findings: Baseline characteristics demonstrated no significant differences between patients with or without thyroid SAID. 29/106 (27.4%) patients developed thyroid sAID between 5 and 51 months following alemtuzumab treatment initiation. 14/29 patients (48.3%) were positive for ThyAb at baseline and developed thyroid sAID. Hazard ratio for time to thyroid autoimmunity was 12.15 (95% Cl 4.73-312) indicating a highly increased risk for ThyAb positive patients. Baseline ThyAb were associated with shorter time to SAID, but not with a specific disease entity of thyroid SAID. Hazard ratios for age, sex, previous treatment, disease duration, disability and smoking status demonstrated no significant association with thyroid autoimmunity. Interpretation: Standard ThyAb-testing for anti-TPO and anti-TG antibodies at baseline was able to indicate increased risk for dinically manifest thyroid SAID and should therefore be used in clinical decisions concerning alemtuzumab treatment initiation. (C) 2019 The Authors. Published by Elsevier B.V.