Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2022) 84 PS3-12-112 | DOI: 10.1530/endoabs.84.PS3-12-112

ETA2022 Poster Presentations Graves’ Disease 2 and Orbitopathy (8 abstracts)

Alemtuzumab-induced graves’ orbitopathy successfully treated with a single dose of rituximab

Francesco Di Marco 1 , Laura Porcaro 2 , Erica Crivicich 1 , Nicola Currò 3 , Maura Arosio 4 , Ilaria Muller 5 & Mario Salvi 6

1Graves Orbitopathy Centre, Endocrine; Fondazione Irccs Ca’ Granda, University of Milan, University of Milan, Milan, Italy; 2Graves Orbitopathy Centre, Endocrine; Fondazione Irccs Ca’ Granda, University of Milan, Italy; 3Ophthalmology, Fondazione Irccs Cà Granda, Ospedale Maggiore Policlinico, Italy; 4Graves’ Orbitopathy Centre, Endocrinology Department, Fondazione Irccs Ca’ Granda, University of Milan, University of Milan, Clinical Sciences and Community Health, Milan, Italy, Milan, Italy; 5University of Milan; Fondazione Irccs Ca’ Granda Policlinico Hospital of Milan, Clinical Sciences and Community Health; Endocrinology; Graves’ Orbitopathy Centre, Milan, Italy; 6Graves Orbitopathy Centre, Endocrine, Fondazione Irccs Ca’ Granda, University of Milan, Milan, Italy

Introduction: The humanized antibody anti-CD52+ alemtuzumab has been approved since 2014 for the treatment of relapsing-remitting multiple sclerosis (RRMS). Immune reconstitution after alemtuzumab induces thyroid autoimmunity in 34-41% of patients with RRMS, with Graves’ disease (GD) accounting for 63-65% of cases. Graves’ Orbitopathy (GO) may also occur in 13% of patients after alemtuzumab and is scarcely reported. Here we present the first case of alemtuzumab-induced GO resistant to high doses of i.v. methylprednisolone and successfully treated with a single low-dose of rituximab.

Case Report: A 37-year-old woman was diagnosed with RRMS in 2009 and initially treated with natalizumab and fingolimod. Alemtuzumab was administered in two courses 12 months apart (2016, 2017). In 2019 she developed GD and was started on methimazole. In 2020 she developed moderate GO and was treated with i.v. methylprednisolone, unsuccessfully. In Dec 2020 she presented clinical-activity-score (CAS) 8/10, proptosis 27.5/28 mm and intermittent diplopia and was treated with 500 mg i.v. rituximab; her CAS improved to 3/10 and 1/10 after one and two months, respectively. In Oct 2021 she underwent total thyroidectomy and in Dec 2021 her GO remained inactive and was scheduled for surgical decompression. Two years after alemtuzumab, her total lymphocytes count had not fully recovered yet (1.06x109/l, n.v. 1.2-3.4). Just before rituximab infusion (3 years post-alemtuzumab), her peripheral B lymphocyte count was still reduced (76 cells/µL, n.v. 100-500) and total B cell depletion occurred immediately after therapy. At the time of thyroidectomy (1 year post-rituximab and 4 years post-alemtuzumab), her B cell numbers were still markedly depleted in both blood and thyroid tissue, compared with control subjects and patients with spontaneous GD. Our patient also presented reduced numbers of T regulatory (Treg) cells in both blood and thyroid tissue compared with controls.

Conclusions: Immune reconstitution after alemtuzumab is known to trigger GD and GO, despite determining a very good control of RRMS. Our patient developed both GD and active GO, despite a post-alemtuzumab B lymphocyte count persistently reduced. Rituximab therapy was effective in inactivating her GO and determined a further reduction of B lymphocytes count. We hypothesize that B cell depletion after rituximab ameliorates GO by interfering with the B cell antigen presentation to T cells. Interestingly, her GO and RRMS remained under control even in presence of reduced counts of Treg. More complete and long-term studies are needed to unravel the immunological mechanism involved in this complex scenario.

Volume 84

44th Annual Meeting of the European Thyroid Association (ETA) 2022

Brussels, Belgium
10 Sep 2022 - 13 Sep 2022

European Thyroid Association 

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