Endocrine Abstracts

Introduction

Medical immunosuppressive treatment of Graves’ orbitopathy (GO) is advised for patents with moderate-severe disease. Steroids represent the mainstay of therapy, as they possess anti-inflammatory activity, but about 20 – 30% of patients are unresponsive and up to 20% of patients may relapse. Immunosuppressive therapeutics alternative to corticosteroids are those targeting the different antigens involved in the pathogenic reactions of GO. Some of these have already been challenged in clinical studies for potential use, although the lack of randomized and controlled trials may at the moment limit their use in clinical practice.

Evidence from studies

Potential targets for therapy in GO are B and T cells, the TSH receptor and the IGF-1 receptor on the fibroblasts, inflammatory cytokines involved in the cascade of immune reactions in the early phase of disease. Consistent open study reports on the efficacy of rituximab have been confirmed by randomized controlled trials. A recent study has shown non inferiority of belimumab, an anti-BAFF monoclonal antibody, with methylprednisolone. Significant improvement of proptosis has been shown with the anti-IGF-1R monoclonal antibody teprotumumab. A recent controlled study has also shown that tocilizumab, an anti-sIL-6R antibody, inactivates GO, and another is underway.

Conclusions

Clinical practice is seeking disease modifying agents in GO as an alternative to steroids, currently standard treatment for GO. Novel therapeutics are currently indicated, especially in patients resistant to steroid or with contraindications to steroids. However, larger randomized controlled trials are needed before these drugs are shown to be more effective and can be approved for routine clinical use in GO.