Progress in immunosuppressive treatment of GO (selenium, steroid dosage, rituximab)
Management of Graves orbitopathy (GO) is a challenge, and 3050% of patients are eventually dissatisfied with medical treatment outcome. GO natural history is poorly understood, but some patients experience a progression of GO over time. Thus, prevention of development/progression by abolishing risk factors (e.g. smoking, thyroid dysfunction) is important. The recent results of a randomized clinical trial (RCT) carried out by the EUGOGO group showed that selenium (sodium selenite for 6 months) prevented progression of mild GO to more severe GO. Selenium, probably acting through antioxidative and immunoregulatory pathways, also caused a significant improvement of preexisting GO compared to placebo. Thus, selenium is a useful tool for prevention of progression and for management of mild GO. Accordingly, a 6-month course of selenium is advisable for patients with mild GO.
Glucocorticoids, preferentially given intravenously, represent the first-line treatment for moderate-to-severe and active GO. The most common regimen employs a cumulative dose of 4.5 g methylprednisolone, subdivided in 12 weekly intravenous infusions. However, evidence concerning the optimal dose in terms of efficacy and side effects is missing. The EUGOGO group has just completed an RCT comparing three different cumulative doses (2.5, 5.0, 7.5 g). Preliminary analysis suggests that the highest dose is more effective (particularly on eye motility) but associated with more major side effects. Thus, for the time being, it is reasonable to say that the dose should be tailored in each patients based on the activity and severity of GO, evaluating potential benefits and risks.
The frequently unsatisfactory response to glucocorticoids underscores the need for novel and more pathogenic treatments. Given the role played by B lymphocytes in GO pathogenesis, rituximab, an agent that depletes CD20-positive B lymphocytes, might be such a drug. Results in the field of GO are preliminary, based on small, uncontrolled studies. But they are promising by showing beneficial effects, mostly in GO patients resistant to conventional glucocorticoid treatment. Two ongoing RCTs (rituximab vs glucocorticoids, rìtuximab vs placebo) should hopefully provide useful information on the efficacy and safety of this expensive drug.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.