The position of monoclonal antibodies and small molecules in the treatment of thyroid orbitopathy.

Since the European Thyroid Association guidelines for the management of thyroid orbitopathy (TO) were published in 2016, a number of randomised clinical trials (RCTs) investigating the use of biologic drugs for the treatment of moderate to severe and active TO have been published. Therefore, new recommendations for its treatment were developed and published in 2021. Treatment of active TO includes 2 types of immunosuppressive agents: non-specific and specific. Specific immunosuppressive agents used to treat TO include adalimumab (ADA), infliximab (IFX), etanercept (ETA), rituximab (RTX), tocilizumab (TCZ), teprotumumab (TEP), and batoclimab (BAT). In the manuscript, we present a review of the literature on RCTs, retrospective studies, and case reports on their use in the treatment of TO. The authors emphasise the beneficial effects of TEP, indicating, however, the lack of data on its long-term efficacy and safety and the lack of head-to-head comparison with i.v. glucocorticosteroids and its huge limitation is also the high price of the drug. TCZ is a therapeutic option for glucocorticosteroid-resistant TO and should be considered for second-line treatment (due to the cost of treatment, among other reasons) or first-line treatment in patients with contraindications to i.v. glucocorticosteroids. Given its side-effect profile, especially some risk of optic nerve neuropathy (DON), RTX is considered by the authors as a second- or even third-line treatment option. The current 2021 European Group on Graves' Orbitopathy (EUGOGO) recommendations include RTX, TCZ, and TEP among the second-line drugs for the treatment of moderate to severe and active TO. BAT is under clinical trials. Given the numerous advantages of biologic drugs over glucocorticosteroids, further RCTs are indicated to confirm their possible place also as first-line treatment in TO.