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Development of autoimmune thyroid disease in multiple sclerosis patients post-alemtuzumab improves treatment response

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Revised manuscript Sovetkina et al (clean version).docxAccepted version1.13 MBMicrosoft WordView/Open
Title: Development of autoimmune thyroid disease in multiple sclerosis patients post-alemtuzumab improves treatment response
Authors: Martin, N
Sovetkina, A
Nadir, R
Scalfari, A
Tona, F
Murphy, K
Rigoni, E
Dorsey, R
Malik, O
Nandoskar, A
Singh-Curry, V
Nicholas, R
Item Type: Journal Article
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.
Issue Date: Sep-2020
Date of Acceptance: 12-Jul-2020
URI: http://hdl.handle.net/10044/1/81405
DOI: 10.1210/clinem/dgaa453
ISSN: 0021-972X
Publisher: Oxford University Press
Start Page: e3392
End Page: e3399
Journal / Book Title: The Journal of Clinical Endocrinology & Metabolism
Volume: 105
Issue: 9
Copyright Statement: © Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. This is a pre-copy-editing, author-produced version of an article accepted for publication in following peer review. The definitive publisher-authenticated version is available online at: https://academic.oup.com/jcem/article/doi/10.1210/clinem/dgaa453/5872006
Keywords: Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
alemtuzumab
autoimmune thyroid disease
multiple sclerosis
secondary autoimmunity
Graves disease
LYMPHOCYTE DEPLETION
FOLLOW-UP
RECONSTITUTION
REMYELINATION
CUPRIZONE
TRIALS
CELLS
Graves disease
alemtuzumab
autoimmune thyroid disease
multiple sclerosis
secondary autoimmunity
1103 Clinical Sciences
1114 Paediatrics and Reproductive Medicine
Endocrinology & Metabolism
Publication Status: Published
Online Publication Date: 2020-07-15
Appears in Collections:Department of Metabolism, Digestion and Reproduction
Faculty of Medicine
Department of Brain Sciences