Tocilizumab in the Treatment of Graves Orbitopathy

Abstract

Introduction: Graves orbitopathy (GO) is an autoimmune inflammatory disease with a challenging and somewhat controversial treatment. Therapeutic options in moderate to severe active disease may include intravenous (iv) corticosteroid therapy, other immunomodulators, radiotherapy or surgical decompression of the orbit. The Clinical Activity Score (CAS) is a clinical scale that quantifies signs and symptoms of the disease, allowing the evaluation of the degree of activity and prediction of clinical response to treatment. Tocilizumab is a humanized monoclonal antibody against the interleukin-6 receptor. Recent studies report its effectiveness in treating active GO refractory to IV corticosteroid therapy. The purpose of this study is to present fourteen cases of GO resistant to IV corticosteroid therapy treated with tocilizumab.

Methods: We conducted a retrospective analysis of fourteen patients with active GO, with a CAS ≥ 4, resistant to IV methylprednisolone treatment. The patients were then submitted to monthly IV treatment with tocilizumab (8 mg/kg weight) for 4 to 8 months. We recorded and analysed visual acuity, CAS, Hertel exophthalmometry, ocular motility, and Trab levels (anti-TSH receptor antibodies) before and after treatment.

Results: We included fourteen patients, with a median age of 47 years (range 37 – 72 years) at the beginning of treatment, and a mean follow-up period of 37 months (range 4 to 48 months). Thirteen of the fourteen patients showed gradual anatomical and functional improvement of GO, with a reduction of the CAS score, decrease Trab levels (median reduction of 5.77 U/L), and decreased (10 of 14 patients) or stabilized proptosis (3 of 14 patients). One patient maintained active disease (CAS ≥ 3) requiring more tocilizumab sessions. However, there are adverse events such as abnormalities in the lipid profile or liver function and increased risk of serious infections. Two patients developed transient neutropenia, which did not require treatment cessation.

Conclusion: Therapeutic options used for moderate to severe active GO, such as corticosteroid therapy or radiotherapy, may provide disappointing results, only offering partial response with the recurrence of the disease. Therefore, the use of new immunosuppressive drugs, such as tocilizumab, with more targeted therapeutic action may show promising results. Despite the reduced sample, our results suggest that tocilizumab can be effective in the treatment of thyroid disease in patients with active GO refractory to corticosteroids.