Incidence, Patterns and Predictors of Alemtuzumab-Induced Thyroid Dysfunction in Patients With Multiple Sclerosis: A Northern Ireland Cohort Study.

BACKGROUND: Alemtuzumab (Lemtrada) is highly effective for selected relapsing multiple sclerosis (MS) but can cause autoimmune thyroid dysfunction (AITD). Our aim was to retrospectively review patients and the monitoring of their thyroid function tests (TFTs) during and after treatment with alemtuzumab. We wanted to summarise the incidence and characterise the nature of TD in our Northern Ireland (NI) cohort. METHODS: Data was obtained from the NI Disease Modifying Treatment (NIDMT) database for all patients with relapsing remitting MS receiving alemtuzumab in the period between 2015 and 2024. Patients were identified and data collected retrospectively from clinical records. Data collected included dates of alemtuzumab treatment, TFT monitoring results, subsequent follow up and any thyroid treatment required. Demographic and clinical data were obtained from the Northern Ireland Electronic Care Record (NIECR)-an electronic healthcare record. RESULTS: 168 patients (female n = 114, male n = 54) received alemtuzumab between 2015 and 2024 in Northern Ireland, with a follow-up period of approximately 60 months. On most recent follow up, TD occurred in 45.8% (n = 77) patients. The spectrum of thyroid disorders observed post-alemtuzumab was diverse; Graves' disease and thyroiditis were the most common thyroid disorders, each affecting 10.7% (n = 18) of patients. Thyroiditis with positive thyroid stimulating receptor antibodies (TRAb) occurred in 7.7% (n = 13), followed by Hashimoto's disease 7.1% (n = 13), with both ab-negative hypothyroidism 6.0% (n = 10) and hyperthyroidism 3.0% (n = 5). Two patients had pre-existing thyroid dysfunction hypothyroidism n = 1 and hyperthyroidism n = 1. Baseline thyroid autoantibody status showed a strong association with TD. Women were twice as likely as men to develop TD following Alemtuzumab treatment. Neither age nor MS duration significantly influenced the risk of TD. TD was diagnosed as early as 12 months after initiating treatment, with the latest diagnosis being made 56 months after. CONCLUSION: The frequency of Alemtuzumab-induced TD in our cohort was similar to that reported in other literature and the nature of TD varied with a number of patients fluctuating between dysthyroid states. This data highlights the importance of close surveillance for TD due to the risk of complex, late-onset autoimmunity.