Potential utility of rituximab for Graves' orbitopathy

Abstract

Context: B-Cell contribution to autoimmunity has been emphasized since the use of B-cell depleting therapies. B cells produce autoantibodies but also activate CD4+ T cells and inflammation and are important antigen-presenting cells. Several cell surface markers are targets on which B cell-depleting agents can act directly.

Evidence acquisition: Targeting of CD20+ cells removes B lymphocytes in all intermediate stages of B-cell maturation, activated memory B, and short-lived plasma cells by depleting their immediate precursors. Rituximab (RTX) has been used off-label in various autoimmune disorders but is approved for clinical use only in non-Hodgkin's lymphoma and rheumatoid arthritis. The rationale of RTX use in Graves' disease is that blockade of pathogenic autoantibody generation might bring about Graves' hyperthyroidism remission.

Evidence synthesis: To date, RTX has been used in 43 patients with active Graves' orbitopathy (GO). Disease has become inactive in as many as 39 (91%), has not changed in three, and worsened in one patient. In most patients, proptosis and eye motility have been shown to improve. Side effects have been reported in about one-third of patients, usually infusion-related reactions. Because RTX does not seem to modify circulating TSH receptor antibodies, its effect may result from the blockade of antigen presentation by B cells after anti-CD20-induced lysis.

Conclusions: Although evidence from controlled trials is needed before proposing RTX as a novel therapeutic tool in this disease, collected data suggest that RTX does significantly affect the activity and severity of GO. Controlled studies will also help decide whether RTX is to be used in any patients with active GO or only in those with otherwise unresponsive disease of a severe degree. The data reported on RTX therapy in GO suggest that B-cell depletion may be pursued shortly after diagnosis, and not only as a therapeutic option when standard immunosuppression has failed.