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Immune reconstitution after alemtuzumab therapy for multiple sclerosis triggering Graves' orbitopathy: a case series.

Accepted version
Peer-reviewed

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Article

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Authors

Roos, Jonathan CP 
Moran, Carla 
Chatterjee, V Krishna 
Jones, Joanne 

Abstract

Alemtuzumab-a monoclonal antibody targeting the CD52 glycoprotein expressed by most mature leucocytes-effectively decreases relapse rate and disability progression in early, relapsing-remitting multiple sclerosis (MS). However, secondary autoimmune disorders complicate therapy in nearly 50% of treated patients, with Graves' disease being the most common. Rarely, thyroid eye disease (TED) ensues; only seven such cases have been reported. Our aim was to analyse the largest series of MS patients developing thyroid eye disease after alemtuzumab treatment. We performed a retrospective chart review of MS patients treated with alemtuzumab (1995-2018) and subsequently identified by their treating physicians as having developed TED and referred to our ophthalmology service. As an original trial centre for alemtuzumab, our hospital has treated approximately 162 MS patients with this novel therapy. In total, 71 (44%) developed thyroid dysfunction, most of whom (87%) developed Graves' disease, with ten (16%) referred for ophthalmological evaluation. Two developed active orbitopathy following radioiodine treatment; one occurred after cessation of anti-thyroid drug treatment. Three developed sight-threatening disease requiring systemic immunosuppression, with one refractory to multiple immunosuppressants. The remaining patients were treated conservatively. TSH-receptor antibody (TRAb) levels were significantly raised in all cases, when ascertained. We report sight-threatening as well as mild TED in MS patients after treatment with alemtuzumab. Endocrine instability, radioiodine treatment and positive TRAb are all likely risk factors. The data support at least 6-monthly biochemical and clinical assessment with a low threshold for referral to an ophthalmologist, particularly for those with higher TRAb levels who may be at greater risk of orbitopathy.

Description

Keywords

Adolescent, Adult, Alemtuzumab, Antineoplastic Agents, Immunological, Autoantibodies, Disease Progression, Enzyme-Linked Immunosorbent Assay, Female, Graves Ophthalmopathy, Humans, Immune Reconstitution, Magnetic Resonance Imaging, Male, Middle Aged, Multiple Sclerosis, Receptors, Thyrotropin, Recurrence, Retrospective Studies, Risk Factors

Journal Title

Eye (Lond)

Conference Name

Journal ISSN

0950-222X
1476-5454

Volume Title

33

Publisher

Springer Science and Business Media LLC
Sponsorship
Wellcome Trust (105924/Z/14/Z)
Wellcome Trust (105924/Z/14/A)
Wellcome Trust (105924/Z/14/Z)
Wellcome Trust (105924/Z/14/A)
Medical Research Council (G1100114)