Endocrine Abstracts

Introduction

Immune reconstitution therapies (IRT), which include antibody-based cell-depleting therapies targeting CD52+ (alemtuzumab) or CD20+ (rituximab, ocrelizumab) leukocytes, are approved for the treatment of multiple sclerosis. Thyroid autoimmunity is a common adverse effect of alemtuzumab treatment, Graves' disease being the most prevalent manifestation. To date, thyroid autoimmunity events have not been reported with CD20 targeting monoclonal antibodies.

Case Report

Fifty-nine-year-old woman with primary progressive multiple sclerosis, non-smoker, with no prior personal history of thyroid disease or autoimmunity (confirmed before the IRT initiation). She was started on ocrelizumab in July 2018; 6 months later, immediately prior to her second ocrelizumab administration, her thyroid function tests revealed an overt hyperthyroidism with strong positivity for TRAb, TPOAb and TgAb; she had no signs of ophthalmopathy. Due to the temporal association of Grave's disease (GD) diagnosis with ocrelizumab infusion, absence of symptoms and our experience with alemtuzumab-induced GD, with a frequently unpredictable course and occasional rapid evolution to hypothyroidism, we decided for an active surveillance strategy and antithyroid drugs were not started. On the following 6 months, she underwent spontaneous resolution of hyperthyroidism with TRAb negativity and a mild and transitory period of subclinical hypothyroidism, while she continued the biannually ocrelizumab administration schedule. To present date, she has maintained close clinical and biochemical surveillance with normal TSH, fT4 and fT3 levels and undetectable TRAb.

Discussion

To our knowledge, this is the first case of GD reported after ocrelizumab administration. The timing of diagnosis, onset and course of the reported case is similar to alemtuzumab-induced GD, usually interpreted as an "immune reconstitution syndrome"; however ocrelizumab cell count depletion is inferior in severity, cell population affected and duration of depletion. An older CD20-targeting therapy, rituximab, has been proposed for treatment of Graves ophthalmopathy; however, although it depletes B-cells it does not reduce TRAb levels making unlikely a sporadic GD ethology, incidentally detected and treated by anti-CD20- targeting therapy. This case highlights the importance of pre-screening and follow-up with thyroid function tests in patients treated with ocrelizumab. As a novel therapeutic antibody, further investigation is required to unravel underneath causes of thyroid autoimmunity with ocrelizumab.