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

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.

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Acknowledgements

The authors would like to thank Mr Cornelius Rene and Dr Paul Meyer for helpful discussions and insights into the management of thyroid eye disease over many years.

Funding

There was no funding sought or obtained for this research. JJ is funded by the Wellcome Trust.

Author contributions

All authors have contributed to the data collection and writing.

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Correspondence to Rachna Murthy.

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Conflict of interest

All authors are doctors who manage patients with thyroid disease, thyroid eye disease or multiple sclerosis. AJC received honoraria and speakers’ fees from Sanofi, up until September 2017. JJ reports receiving speaker honoraria and consulting fees from Sanofi.

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As an anonymised retrospective chart review no institutional review board authorisation was necessary.

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Dr Murthy serves as guarantor of this work. It is an honest, accurate, and transparent account of the study being reported; no important aspects of the study have been omitted.

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