Alemtuzumab-related thyroid disease in people with multiple sclerosis is associated with age and brainstem phenotype at disease onset

Abstract

Background Autoimmune thyroid disease (AITD) occurs in 40%–50% of alemtuzumab-treated persons with multiple sclerosis (pwMS), most of whom will develop Graves’ Disease (GD). Objective To explore contributory factors for alemtuzumab-related AITD in pwMS. Methods A retrospective patient chart review was performed. Results Sixteen out of 52 (30.8%) pwMS developed AITD. GD occurred in 56.3% ( n = 9), the majority ( n = 7, 77.8%) symptomatic. All but one (85.7%) pwMS with symptomatic GD developed atypical, large and rapid fluctuations in thyroid hormone levels unexplained by effect of anti-thyroid medication alone. All symptomatic GD cases were age ≤32 years when starting alemtuzumab (ɸ = 0.60, p = 0.03). PwMS who started alemtuzumab at a younger age developed thyroid disease earlier ( r = 0.51, p = 0.04). PwMS with clinical and radiological evidence of brainstem involvement at onset of multiple sclerosis were 11 times more likely to develop symptomatic GD compared with those with other phenotypes ( p < 0.01). Conclusion Alemtuzumab-induced reconstitution GD may result from early and increased cross-reactivity between antigens common to the brainstem and thyroid, or presence of shared Human Leukocyte Antigen (HLA) alleles that determine brainstem and thyroid involvement. We suggest cautious use of alemtuzumab in younger (≤32 years) pwMS with early brainstem involvement, especially those actively planning pregnancy, where alternative therapies are readily available.