Quality of Life Improves with Alemtuzumab Over 6 Years in Relapsing-Remitting Multiple Sclerosis Patients with or without Autoimmune Thyroid Adverse Events: Post Hoc Analysis of the CARE-MS Studies

Abstract

Introduction: In clinical trials of alemtuzumab, autoimmune thyroid adverse events (AEs) were frequent. Here, we assess the impact of thyroid AEs on health-related quality of life (HRQL) in alemtuzumab-treated patients with relapsingremitting multiple sclerosis (RRMS). Methods: In phase 3 CARE-MS I (NCT00530348) and II (NCT00548405) trials, patients with RRMS were administered alemtuzumab 12 mg/day on 5 consecutive days at baseline and on 3 consecutive days 12 months later. Patients could participate in an extension study (NCT00930553) through year 6. HRQL was assessed at baseline and annually using the Functional Assessment of Multiple Sclerosis (FAMS), EuroQoL-5 Dimension Visual Analog Scale (EQ-5D VAS), and 36-Item Short-Form Survey (SF-36) questionnaires. Outcomes were Digital features To view digital features for this article go to

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

“…Defining the final analysis dataset as those with at least 1 thyroid event in 6 years where agreement of all 5 domains constituted consensus and excluding those with pre-existing events or those where the event occurred after 6 years, resulted in a dataset of 286 patients representing a 35.3% incidence. While this is lower than the 40%–46% incidence over similar time periods in these and other studies, 4,6,16–18,22 the incidence was 39.8% excluding the 62 patients for whom consensus was not reached, and the 30 who were excluded for pre-existing or post–6-year events. For IFNbeta-1a, the incidence rate of confirmed cases was 4.1%, and 4.3% excluding the 9 patients for whom consensus was not reached and the 5 who had pre-existing events.…”

“…As reported previously, 16 811 patients with RMS were treated with alemtuzumab 12 mg in the CARE-MS I ( n = 376) and CARE-MS II ( n = 435) studies, of which 742 (91.5%) entered the extension study and 659 (81.3%) remained on study for ≥6 years.…”

“…Similarly, health-related quality of life outcomes in patients from CARE-MS I/CARE-MS II/extension studies over 6 years in those with and without thyroid events were similar for those with non-serious AEs, although quality of life worsened toward the end of the study in those with more serious thyroid AEs who were treated with radioiodine or thyroidectomy. 16 By contrast, Sovetkina et al reported significantly fewer relapses, longer relapse-free survival, and reduced disability progression over 2 years in alemtuzumab-treated MS patients with thyroid autoimmunity versus those without. 34 There are several important differences between Sovetkina et al and our study that could explain these disparate findings, including a much smaller sample size ( n = 33 patients with thyroid AEs versus n = 286 in our study), higher baseline EDSS score (mean 4.5 for patients with thyroid AEs versus 2.4 in our study), and higher percentage of patients treated with carbimazole (66.7% versus 8.4% in our study), a drug with considerable anti-inflammatory properties.…”

“…However, analysis of depletion/repopulation kinetics of the major lymphocyte subpopulations affected by alemtuzumab shows no correlation with non-MS autoimmunity, although the repopulation of specific cells that drive autoimmunity remains undetermined. 11 The most common post-alemtuzumab non-MS autoimmunity is thyroid autoimmunity, which was reported in 42% of patients over 6 years in the pooled CARE-MS I/CARE-MS II/extension studies 16,17 and in 41% of patients over 7 years in the CAMMS224 and SM3 studies 18 ; incidence peaked 3 years after initial treatment and declined thereafter. Thyroid autoimmunity incidence was not related to the number of alemtuzumab courses received; at 6 years, incidence was 43%, 41%, 42%, and 38% for those receiving 2, 3, 4, and 5-6 courses, respectively.…”

The Meaning of Immune Reconstitution after Alemtuzumab Therapy in Multiple Sclerosis

“…The results show the outcome of the "early relapsers" improved after completing the second alemtuzumab course, supporting the fact that administering the approved two-course regimen should maximize the clinical benefit [34]. A 2019 study [35] shows that quality of life of patients treated with alemtuzumab ameliorates over a six year post-alemtuzumab treatment period, regardless the independently the occurrence of autoimmune thyroid adverse events.…”