Evaluation of Hepatitis B Virus in Clinical Trials of Baricitinib in Rheumatoid Arthritis
Although hepatitis B virus (HBV) reactivation was seen in patients with RA treated with DMARDs, including BARI, who had serology suggestive of prior infection, reactivation was transient even with continued BARI treatment and did not account for any clinically relevant AEs.
Reactivation of HBV replication is a recognised complication in patients receiving biologic agents for RA, such as DMARDs. Limited data exist on prevalence of occult infection and the incidence of reactivation in RA patients treated with JAK inhibitors. Reactivation of HBV replication can be transient and clinically silent in RA patients, but it can also be severe and may result in acute hepatic failure. The aim of this study was to assess HBV reactivation in clinical trials of BARI.
In pooled analysis of four Phase 3 and one LTE study, with all patients receiving at least one dose of BARI, a total of 269 of 2890 patients had baseline serology suggestive of prior hepatitis B infection. When 290 patients underwent HBV DNA testing post-baseline (215 hepatitis B core antibody (HBcAb)+ and 75 HBcAb- at baseline), 36 (12%) had detectable HBV DNA at some point following treatment. A total of 32 (14.9%) were HBcAb+ at baseline, eight of which (3.7%) had a single quantifiable result (31–1547 IU/mL). Four patients met the definition of reactivation of HBV (HBV DNA level ≥100 IU/mL), but only 3 of 8 received antiviral treatment. There was no clinical evidence of hepatitis and all had AST and ALT levels within normal limits, suggesting that patients with prior HBV infection without clinical indications of active infection can be treated with DMARDs, including BARI, while monitoring for potential reactivation.
Additional data will be needed to fully characterize the potential risk for reactivation of HBV in the context of JAK inhibitors administered in an RA population.