Endocrine Abstracts

Objectives: To identify risk factors for the development of Graves’ Orbitopathy (GO) in patients with Relapsing Remitting Multiple Sclerosis (RRMS) treated with Alemtuzumab, as well as to analyze the clinical behavior of this entity based on a case series.

Methods: Retrospective observational study with real-life data. Patients with RRMS who received at least one cycle of Alemtuzumab in the period 2014-2022 in aMS reference unit in Spain were included. During post-treatment follow-up, the development of Graves’ disease (GD) and GO was documented in the included cases, being assigned to one of three possible subgroups: a) No GD or GO, b) GD without GO, c) GD and GO.

Results: 134 patients were included. Mean follow-up was 5.98 years (SD:3.23) since initiation of Alemtuzumab. 90/134 cases (67.1%) had neither GD nor GO, 38/134 (28.4%) had GD without GO and 6/134 (4.5%) had GD and GO. The incidence of GO in patients with GD was 13.64% (n=6/44). The annual of pre-Alemtuzumab outbreak rate was higher in the group that developed GO (2.4 vs 1.39 GD-noGO and 1.38 noGD-noGO, P=0.03), as was the presence of first-degree family history of autoimmune hypothyroidism (33.3% vs 13.2% GD-noGO and 5.2% noGD-noGO, P=0.017). Cases that developed GO presented with respect to the GD-noGO group higher levels of f-T4 (4 vs 2.3 ng/dl, P=0.009), f-T3 (13 vs 6.2 pg/ml, P=0. 033) and TRab (34.77 vs 16.27 IU/l, P=0.016), in addition to clinical symptomatology (83.3% (n=5/6) vs 38.9% (n=14/38), P=0.04) and goiter (83.3% (n=5/6) vs 23.5% (n=8/38), P=0.01). The need for total thyroidectomy was higher in the group that developed GO (66.7% (n=4/6) vs 18.4% (n=7/38), P=0.027). Of the 6 diagnosed cases of GO, n=3 were moderate/severe and active forms (mean CAS: 4.3 points). Treatment with Tocilizumab (anti-IL6) was indicated in all of them due to refractoriness to corticosteroid treatment (n=1/3) or contraindication to it (n=2/3). In all three cases, inactivation of the disease (CAS<3) was documented after Tocilizumab, with improvement of proptosis and palpebral retraction. No retraction surgery was indicated in any case.

Conclusions: The presence of first-degree relatives with hypothyroidism, a high annual baseline outbreak rate or the development of GD with high levels of f-T4, f-T3 and TRAb can be considered risk factors for the development of GO in patients treated with Alemtuzumab. Treatment with Tocilizumab may be a useful option in the treatment of cases with elevated activity index.