Endocrine Abstracts

Introduction: Alemtuzumab is a monoclonal antibody targeting the CD52 glycoprotein, which is expressed by most mature leucocytes. In early relapsing-remitting multiple sclerosis (MS) alentuzumab effectively decreases relapse rate and disability progression. However, nearly 50% of the pacients treated with alentuzumab develop secondary autoimmune disorders, being Graves’ disease the most common. The development of thyroid eye disease is unusual.

Aims and Methods: We performed a retrospective chart review with MS and alemtuzumab-induced autoimmune hyperthyroid disease (AH-IA), who developed thyroid eye disease after alemtuzumab treatment. All patients with MS who had received at least one cycle of treatment with Alemtuzumab between 2014 and 2020 in Virgen Macarena University Hospital (Seville, Spain) were included.

Results: Our hospital is a regional referral center for MS, so approximately 121 MS patients were treated with alemtuzumab. 41 (33,9%) developed Graves’ disease and 6 (14,6%) were referred for ophthalmological evaluation. Of these, only one presented as a severe case, while the other five presented a mild course. Five were non-smokers at the time of developing ocular signs and symptoms. Five had significantly raised TRAb (> 10 IU/l) at presentation with eye disease—the sixth presented at a time prior to this test being routinely available. There was a 5:1 ratio of females to males. All patients initially received treatment with antithyroid drugs to control thyroid function. Four of them underwent total thyroidectomy as a definitive treatment. At diagnosis of orbitopathy, all patients had thyroid dysfunction consistent with hyperthyroidism. Four patients underwent conservative management with lubricants and selenium. One patient required treatment with oral corticosteroids. The most severe case was a 30-year-old woman who presented with constant diplopia, palpebral retraction >1.5 mm, severe soft tissue involvement, and exophthalmos. With a clinical activity score (CAS) of 3 she was started on treatment with i.v corticosteroids. Due to poor evolution, and an increase in the clinical activity score to 6, she started treatment with Tocilizumab, a humanized MAB against the interleukin (IL)-6 receptor approved as second-line treatment for moderate to severe and active glucocorticoid-resistant Graves’ orbitopathy (GO). At 6 months, she presented great clinical improvement, with a CAS of 2 points (inactive GO).

Conclusions: We report the risk of developing GO in patients with MS treated with alemtuzumab who developed GD. In a novel way not described to date in the literature, we present a case of severe and active GO resistant to glucocorticoids in which Tocilizumab was successfully used.