Development of Autoimmune Thyroid Disease in Multiple Sclerosis Patients Post-Alemtuzumab Improves Treatment Response

Abstract

Context Alemtuzumab is an anti-CD52 monoclonal antibody used in the treatment of relapsing-remitting multiple sclerosis (MS). Between 20-40% of alemtuzumab-treated MS patients develop autoimmune thyroid disease (AITD) as a side effect. Objective To determine whether MS disease progression following alemtuzumab treatment differs in patients that develop AITD compared to those who do not. Design, setting and patients A retrospective analysis of 126 patients with relapsing-remitting MS receiving alemtuzumab from 2012 to 2017 at a tertiary referral centre. Main outcome measures Thyroid status, new relapses, Expanded Disability Status Score (EDSS) change and disability progression following alemtuzumab were evaluated. Results Twenty-six percent (33 out of 126, 25 female, 8 male) of alemtuzumab-treated patients developed AITD, 55% of which was Graves’ disease. EDSS score following alemtuzumab was reduced in patients who developed AITD compared to those who did not (median [IQR]; AITD: -0.25 [-1 - 0.5] vs non-AITD: 0 [1 - 0]. P=0.007]. Multivariate regression analysis confirmed that the development of AITD was independently associated with EDSS score improvement (p=0.011). Moreover, AITD patients had higher relapse-free survival following alemtuzumab (p=0.023). There was no difference in the number of new focal T2-lesions and contrast-enhancing MRI lesions developed following alemtuzumab between the two groups. Conclusion Graves’ disease was the most common form of AITD developed by MS patients following alemtuzumab. This study suggests that MS patients who develop AITD may have an improved response to alemtuzumab, as measured by reduced disability and lower relapse rate.

Prevalence, Risk Factors, and Clinical and Biochemical Characteristics of Alemtuzumab-Induced Graves Disease

“…Development of GD after alemtuzumab treatment was associated with reduced risk of new MS attacks and lesions on MRI, consistent with earlier findings ( 20 ). The mechanism for this remains unclear but is interesting from an immunological standpoint.…”

The role of autoimmune antibodies to predict secondary autoimmunity in patients with relapsing-remitting multiple sclerosis treated with alemtuzumab: A nationwide prospective survey

“…However, this finding was not supported by reductions in the rates of relapse or lesion formation on MRIs. In contrast, a previous study showed that both disability and disease activity were reduced in patients with AITD post-ALZ compared to patients without AITD ( 48 ). Estimating disability with EDSS at specific time points is less reliable compared to CDW due to intra- and inter-rater variability and to the short-term impact of relapses ( 12 , 49 , 50 ).…”

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

“…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. 35 Future research should ascertain whether pre-treatment disability status or carbimazole use influences MS outcomes for alemtuzumab-treated patients.…”