Rituximab, adalimumab, etanercept, tocilizumab: are biologics the future for Graves' orbitopathy?

Graves' orbitopathy (GO) is the main extrathyroidal manifestation of Graves disease and a rare disease in its severe expressions. Moderate-to-severe GO represents a therapeutic challenge. Established nonsurgical treatments include glucocorticoids (most commonly given intravenously), cyclosporine, and orbital radiotherapy. However, results are not always satisfactory, and a relevant proportion of GO patients need some kind of rehabilitative surgery (orbital decompression, squint surgery, eyelid surgery) once GO is inactivated. Biological agents have been used in several autoimmune disorders, with contrasting results. Current better understanding of the pathogenesis of GO allows us to identify pathways that might be the target of biologics. T and B cells, cytokines, and peroxisome proliferator-activated receptor-γ might all be targeted by treatments. It is extremely difficult to design and perform sufficiently powered randomized controlled studies that may support the role of targeted therapies. For the time being, rituximab, a monoclonal antibody depleting CD20-positive B cells, appears the most promising agent, but so far its use relies on the results of small and uncontrolled studies.