SAT-429 Systemic Safety Analysis of Mycophenolate in Graves’ Orbitopathy

Abstract

ContextThe dual antiproliferative mechanism of mycophenolate appears to be beneficial in Graves’ orbitopathy (GO).MethodsThe safety data, which is of utmost importance in immunomodulation, from the two major randomized mycophenolate trials [“Chinese trial” (1) and “European Group on Graves’ Orbitopathy (EUGOGO) trial” (2)] and the original database of the EUGOGO trial were systematically analyzed. Treatment efficacy stratified by individual visual parameters of clinical disease activity and severity were also compared.ResultsA total of 129 adverse events (AE) involving 50 patients (29.4%) were noted among all mycophenolate-treated patients. Mycophenolate sodium plus intravenous glucocorticoid (MPS+GC) group of the EUGOGO trial recorded significantly more AE (55.4% versus 4.6% of patients affected) and serious adverse events (SAE) (12.5% versus 0%) than mycophenolate mofetil (MMF) group of the Chinese trial. The excess of AE may partly be contributed by GC use. None of those SAE was side effect (SE). Most SE in MPS+GC group (79%) were mild. Gastrointestinal disorders, infection and liver dysfunction affected 8.8%, 7.1% and 1.2% of all mycophenolate-treated patients (versus 5.4%, 5.4% and 1.2% of all patients on GC monotherapy, respectively). When compared to GC monotherapy, MPS+GC did not significantly increase the overall SE rate (25.3% versus 19.7%) nor did risks of infection or liver dysfunction, but it result in more mild gastrointestinal disorders (SE rate in EUGOGO trial 10.8% versus 4.9%). No cytopenia, serious infection, severe hepatotoxicity or treatment related mortality was reported among mycophenolate-treated patients. The much higher AE rates of mycophenolate trials in other autoimmune diseases or transplantations suggested that major mycophenolate toxicities were mostly dose- and duration-dependent. Regarding efficacy, mycophenolate achieved better overall response than GC monotherapy. Approximately 70% (versus 90% in MMF group) and 30% (versus 60–70% in MMF group) of patients in MPS+GC group achieved endpoints in most individual visual parameters of activity and severity, respectively. MPS+GC group of the EUGOGO trial performed better than MMF group in terms of improvement of pain and eye movement.ConclusionsThe risk-benefit ratio of 6-month courses of low dose mycophenolate treatment in active moderate-to-severe GO, either as monotherapy or as combination with GC, is highly favorable given its reassuring safety profile with low rate of mild to moderate SE and promising efficacy.