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      Rituximab in the treatment of Graves’ orbitopathy: latest updates and perspectives

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          Abstract

          Graves’ orbitopathy (GO) is a potentially sight-threatening and disfiguring, extrathyroidal manifestation of Graves’ disease. It often impairs patients’ quality of life, causing severe social and psychological sequelae. Intravenous glucocorticosteroids is currently the mainstay of therapy, but the efficacy is often underwhelming and recurrence rate is high. For many years, clinicians have been searching for new methods of treatment. Rituximab (RTX) is a chimeric monoclonal antibody targeted against CD20 which is a surface antigen present on B cells. It is frequently used to treat non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, or various types of vasculitis. Numerous clinical trials employing RTX in the treatment of GO have shown promising results. RTX is currently considered to be a valid second-line treatment option in patients unresponsive to previous interventions or in disease reactivation. This review summarizes the available literature on this topic, including two largest, randomized, controlled studies. Potential benefits, as well as the limitations of RTX therapy, are discussed.

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          Most cited references61

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          Graves' ophthalmopathy.

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            THE 2021 EUROPEAN GROUP ON GRAVES’ ORBITOPATHY (EUGOGO) CLINICAL PRACTICE GUIDELINES FOR THE MEDICAL MANAGEMENT OF GRAVES’ ORBITOPATHY

            Graves’ orbitopathy (GO) is the main extrathyroidal manifestation of Graves’ disease (GD). Choice of treatment should be based on assessment of clinical activity and severity of GO. Early referral to specialized centers is fundamental for most patients with GO. Risk factors include smoking, thyroid dysfunction, high serum level of thyrotropin receptor antibodies, radioactive iodine (RAI) treatment, and hypercholesterolemia. In mild and active GO, control of risk factors, local treatments and selenium (selenium-deficient areas) are usually sufficient; if RAI treatment is selected to manage GD, low-dose oral prednisone prophylaxis is needed, especially if risk factors coexist. For both active moderate-to-severe and sight threatening GO, antithyroid drugs are preferred when managing Graves’ hyperthyroidism. In moderate-to-severe and active GO, intravenous (iv) glucocorticoids are more effective and better tolerated than oral glucocorticoids. Based on current evidence and efficacy/safety profile, costs and reimbursement, drug availability, long-term effectiveness and patient choice after extensive counselling, a combination of iv methylprednisolone and mycophenolate sodium is recommended as first-line treatment. A cumulative dose of 4.5 grams (g) of iv methylprednisolone in 12 weekly infusions is the optimal regimen. Alternatively, higher cumulative doses not exceeding 8 g can be used as monotherapy in most severe cases and constant/inconstant diplopia. Second-line treatments for moderate-to-severe and active GO include: a) a second course of iv methylprednisolone (7.5 g) subsequent to careful ophthalmic and biochemical evaluation, b) oral prednisone/prednisolone combined with either cyclosporine or azathioprine; c) orbital radiotherapy combined with oral or iv glucocorticoids, d) teprotumumab; e) rituximab and f) tocilizumab. Sight threatening GO is treated with several high single doses of iv methylprednisolone per week and, if unresponsive, with urgent orbital decompression. Rehabilitative surgery (orbital decompression, squint and eyelid surgery) is indicated for inactive residual GO manifestations.
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              Teprotumumab for the Treatment of Active Thyroid Eye Disease

              Thyroid eye disease is a debilitating, disfiguring, and potentially blinding periocular condition for which no Food and Drug Administration-approved medical therapy is available. Strong evidence has implicated the insulin-like growth factor I receptor (IGF-IR) in the pathogenesis of this disease.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                11 October 2022
                01 December 2022
                : 11
                : 12
                : e220303
                Affiliations
                [1 ]Department of Endocrinology , Diabetology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland
                [2 ]Clinical Research Centre , Medical University of Bialystok, Bialystok, Poland
                Author notes
                Correspondence should be addressed to J Supronik: jakub.supronik@ 123456uskwb.pl
                Author information
                http://orcid.org/0000-0002-3422-4382
                Article
                EC-22-0303
                10.1530/EC-22-0303
                9716394
                36219838
                8ac4524f-3642-43be-a9c3-aaaebd1e16ec
                © The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 19 September 2022
                : 11 October 2022
                Categories
                Review

                graves’ orbitopathy,rituximab,thyroid eye disease,graves’ disease

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