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  • Oculoplastics/Orbit

    Review of: The 2021 European Group on Graves' orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves' orbitopathy

    Bartalena L, Kahaly G, Baldeschi L, et al. European Journal of Endocrinology, August 2021

    The European Group on Graves’ Orbitopathy has released its 2021 guidelines on the medical management of Graves orbitopathy, updating the 2016 edition.

    Study design

    An ad hoc task force of experts, selected by the European Group on Graves’ Orbitopathy (EUGOGO) executive committee, developed the update to the EUGOGO 2016 guidelines on the medical management of Graves orbitopathy (GO, or thyroid eye disease [TED]). The GRADE system was used to make recommendations and express the quality of the evidence. Recommendations were designated as strong or weak, and evidence was graded as very low quality, low quality, moderate quality, and high quality.


    Intravenous methylprednisolone (IVMP) in combination with oral mycophenolate sodium (MMF) is strongly recommended as first-line treatment for active moderate-to-severe GO. In the more severe forms of active moderate-to-severe GO, including constant/inconstant diplopia, severe inflammatory signs, and exophthalmos >25 mm, IVMP at the highest cumulative dose (7.5 g per cycle) as monotherapy is an additional valid first-line treatment.

    Second-line treatments for active moderate-to-severe GO include: a second course of IVMP monotherapy, starting with high single doses (0.75 g) and a maximal cumulative dose of 8 g per cycle; oral prednisone/prednisolone combined with either cyclosporine or azathioprine; orbital radiotherapy combined with oral or intravenous glucocorticoids; teprotumumab; rituximab; or tocilizumab.

    The task force strongly recommends that sight-threatening GO be treated immediately with high-dose IVMP (0.5–1 g daily for 3 consecutive days or every other day), and then with urgent orbital decompression if response is absent or poor within 1–2 weeks. All recommendations are graded as moderate quality.


    This study is limited by the quality of evidence reviewed. The recommendations for the treatment of active moderate-to-severe and sight-threatening GO were all supported by moderate-quality evidence only. Additionally, biologic therapies were all considered second-line therapies due to a lack of data from large randomized controlled trials against the current standard of care (IVMP ± MMF), as well as their availability and cost and the lack of long-term data regarding the need for subsequent rehabilitative surgery. As important, teprotumumab is approved only in the United States and not in Europe; therefore, it is expected that it would not be recommended as a primary treatment in Europe. These guidelines do not reflect the current practice in the United States, where teprotumumab is often considered a first-line therapy (in addition to IVMP) for active moderate-to-severe GO.

    Clinical significance

    The 2021 EUGOGO guidelines for active moderate-to-severe and sight-threatening GO can help guide management in Europe, particularly for endocrinologists. The evidence in support of the combination of IVMP and MMF over IVMP monotherapy is notable and may change practice patterns. The lack of use and approval of teprotumumab in Europe limits the application of these guidelines to US practice. American guidelines for GO management are needed to more accurately reflect the availability and use of teprotumumab and other biologics.