Immunotherapy for Graves' ophthalmopathy

Curr Opin Endocrinol Diabetes Obes. 2014 Oct;21(5):409-14. doi: 10.1097/MED.0000000000000097.


Purpose of review: In recent years, immunosuppressive therapy, as an alternative to corticosteroids, has been proposed as novel agents which target the various antigens involved in the pathogenesis of Graves' ophthalmopathy. Although the lack of randomized and controlled studies suggests caution in generalizing results, some data show interesting results.

Recent findings: Potential targets for immune therapy in Graves' ophthalmopathy are the antigens expressed on the target organ of inflammation, namely the receptor and the insulin growth factor -1 receptor on fibroblasts, inflammatory cytokines, and B and T cells. The most promising results are observed with small thyroid stimulating hormone receptor molecules interacting with the receptor on thyrocytes and fibroblasts and with the anti-IGF-1 receptor antibody teprotumumab. A recent open study with tocilizumab, an anti-soluble interleukin-6 receptor, has shown inactivation of Graves' ophthalmopathy. Consistent reports on the efficacy of rituximab will have to be confirmed by randomized controlled trials, which are now in progress.

Summary: Current clinical practice for Graves' ophthalmopathy will greatly benefit from the availability of immunosuppressors that act as disease-modifying drugs, as compared to steroids, the current standard treatment for Graves' ophthalmopathy. Rituximab seems to be a good candidate, as preliminary results from ongoing randomized trials suggest good efficacy with a relative well tolerated profile.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Blocking / immunology
  • Antibodies, Blocking / pharmacology
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal, Murine-Derived / pharmacology*
  • Fibroblasts / drug effects
  • Graves Ophthalmopathy / drug therapy*
  • Graves Ophthalmopathy / immunology
  • Humans
  • Immunotherapy* / methods
  • Inflammation / drug therapy*
  • Inflammation / immunology
  • Randomized Controlled Trials as Topic
  • Receptor, IGF Type 1 / antagonists & inhibitors*
  • Rituximab
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*


  • Antibodies, Blocking
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Tumor Necrosis Factor-alpha
  • Rituximab
  • Receptor, IGF Type 1