Endocrine and multiple sclerosis outcomes in patients with autoimmune thyroid events in the alemtuzumab CARE-MS studies

Abstract

Background Alemtuzumab is an effective therapy for relapsing multiple sclerosis. Autoimmune thyroid events are a common adverse event. Objective Describe endocrine and multiple sclerosis outcomes over 6 years for alemtuzumab-treated relapsing multiple sclerosis patients in the phase 3 CARE-MS I, II, and extension studies who experienced adverse thyroid events. Methods Endocrine and multiple sclerosis outcomes were evaluated over 6 years. Thyroid event cases, excluding those pre-existing or occurring after Year 6, were adjudicated retrospectively by expert endocrinologists independently of the sponsor and investigators. Results Thyroid events were reported for 378/811 (46.6%) alemtuzumab-treated patients. Following adjudication, endocrinologists reached consensus on 286 cases (75.7%). Of these, 39.5% were adjudicated to Graves’ disease, 2.5% Hashimoto's disease switching to hyperthyroidism, 15.4% Hashimoto's disease, 4.9% Graves’ disease switching to hypothyroidism, 10.1% transient thyroiditis, and 27.6% with uncertain diagnosis; inclusion of anti-thyroid antibody status reduced the number of uncertain diagnoses. Multiple sclerosis outcomes of those with and without thyroid events were similar. Conclusion Adjudicated thyroid events occurring over 6 years for alemtuzumab-treated relapsing multiple sclerosis patients were primarily autoimmune. Thyroid events were considered manageable and did not affect disease course. Thyroid autoimmunity is a common but manageable adverse event in alemtuzumab-treated relapsing multiple sclerosis patients. ClinicalTrials.gov Registration Numbers: CARE-MS I (NCT00530348); CARE-MS II (NCT00548405); CARE-MS Extension (NCT00930553)

Safety and efficacy with alemtuzumab over 13 years in relapsing-remitting multiple sclerosis: final results from the open-label TOPAZ study

“…17 Data from long-term trials, including TOPAZ and post-marketing studies, show that the benefit-risk profile of alemtuzumab becomes more favorable over time as AE incidence declines. 18–20 In a previous analysis of TOPAZ data, participants receiving additional courses of alemtuzumab had a consistent safety profile up to Year 8 compared with those who received two courses and the overall study cohort. 20 There was no evidence of increased rates of infections, malignancies, or autoimmune AEs with additional alemtuzumab courses.…”

“…It is important to note that these results may be influenced by a possible lead bias resulting from AEs with delayed onset, particularly thyroid AEs which are most commonly reported within 2 years after a course of alemtuzumab. 11,19 Further insights on the timing of additional alemtuzumab courses and other best practices for maximizing safety are expected to arise from ongoing, prospective real-world studies. 18,21 Efficacy results from the present phase III/IV studies support previous findings.…”