Characterization of auto-immune hepatitis associated with the use of anti-TNFα agents: An analysis of 389 cases in VigiBase

Auto-immune diseases, including auto-immune hepatitis may be associated with the use of drugs, such as anti-TNF-alpha inhibitors. The aim of the study was to analyze the characteristics of anti-TNF-alpha inhibitor-associated autoimmune hepatitis (ATIAIH) in a large international pharmacovigilance database. We analyzed all ICSRs classified as Autoimmune hepatitis according to the Medical Dictionary for Drug Regulatory Activities term (preferred term level) in VigiBase, the World Health Organization global pharmacovigilance database of adverse drug reactions collected by national drug authorities in > 130 countries ( > 90% of the world population). Bayesian disproportionality analysis was used to compute IC025, which is the lower end of the 95% credibility interval for the association between a suspected treatment and an adverse event. IC025 > 0 are considered statistically significant. A total of 389 ATIAIH ICSRs were identified. The median age at ATIAIH onset was 44 years and the female to male sex ratio was 3.72. Infliximab (IC025 = 2.98), adalimumab (IC025 = 0.32) and etanercept (IC025 = 0.19) yielded a statistically significant signal in disproportionality analysis. Infliximab was the most frequently involved drug (50.1%). The median treatment duration before ATIAH occurrence was 4.9 months. ATIAIH was reported as serious adverse event in 91%. Death (directly linked to AIH or not) occurred in 10 cases (2.9% of ICSRs). The most frequent reported indication for anti-TNF-alpha agent was rheumatoid arthritis (31.9%). This study enables the identification and a detailed study of 389 new cases of ATIAIH and confirms a significant association of ATIAIH with infliximab, adalimumab and etanercept.