Rituximab for the Treatment of Graves’ Orbitopathy

Abstract

The contribution of B cells to human autoimmune disease has recently been underscored because of the therapeutic benefit of B-cell depleting therapies. B cells are involved in the production of autoantibodies and in CD4+ T-cell activation and control of T-cell function and inflammation, through cytokine production. B cells are also important antigen presenting cells. Rituximab (RTX) has been used off-label in various autoimmune disorders and has been shown to effectively deplete mature and memory CD20+ B cells, but not long-lived plasma cells. The rationale of RTX use in Graves’ disease (GD) and Graves’ orbitopathy (GO) relies on its putative effect on pathogenic autoantibodies causing hyperthyroidism. RTX in patients with active GO has been shown to significantly affect the inflammatory activity and severity of GO. Caution is suggested before proposing RTX as a novel therapeutic tool in this disease until randomised controlled studies are available. Should preliminary observations be confirmed, an optimal strategy for controlling the progression of GO would be to pursue B-cell depletion shortly after diagnosis and not as an additional therapeutic option when standard immunosuppression has failed.