Abatacept induced granulomatous hepatitis with a sarcoidosis- like reaction: a blinded trial in mice

BACKGROUND: Abatacept is increasingly used for rheumatoid arthritis (RA) and juvenile idiophathic arthritis (JIA) treatment. However little is known about the risk of hepatotoxicity. The aim of this study was to determine whether the inhibition of the T cell CD28 receptor by abatacept results in acute hepatitis in BALB/c mice. METHODS: Twenty BALB/c mice were studied. Ten mice received subcutaneous (SC) injection of abatacept (0.25mg per 25g body weight per 0.03 ml normal saline) at 0, 2, 4 and 8 weeks. For the control group, 10 mice received a SC injection of normal saline (NS) (0.03 ml). At the 10th week post injection, the mice were sacrificed, and histopathological studies were conducted. RESULTS: Of the abatacept-treated group, 3/10 mice died. Liver histology for the abatacept-treated group showed that 6/7 displayed histopathological changes in the lobular cellular infiltrates of eosinophils, lymphocytes and histiocytes, in addition to granuloma formation. In contrast, only minimal inflammation was observed in 3/10 mice in the control group (p=0.036). CONCLUSION: Abatacept may play a role in inducing granulomatous hepatitis with a sarcoidosis-like reaction. Additional data including transaminases, antinuclear antibodies (ANA), Antimitochondrial antibodies (AMA) and other auto antibodies should be tested.