Hepatic safety in patients with rheumatoid arthritis treated with baricitinib: post-hoc analysis from clinical studies

Background: Latent tuberculosis infection (LTBI) and hepatitis B virus (HBV) reactivation are important issues in the management of rheumatoid arthritis patients. Isoniazid (INH) plays a vital role in controlling TB but it may result in hepatic abnormalities. We present hepatic safety and HBV reactivation in patients with RA treated with baricitinib (BARI). Methods: Hepatic safety with INH treatment was analyzed in data from 3 placebo (PBO)‐controlled Phase 3 studies, and HBV analyses included additional Phase 3 and a long‐term extension studies. Respectively, changes in alanine aminotransferase (ALT) levels (≥1X/≥3X/≥5X/≥10X ULN) from baseline up to 24 weeks; and HBV surface antigen, core antibody (HBcAb), surface antibody (HBsAb), and HBV DNA at baseline or post‐baseline, were analyzed. Results: (1).

INH:

Total, 2516 patients were treated with BARI 4‐mg/BARI 2‐mg/adalimumab (ADA)/PBO. Background csDMARDs were continued. Overall, 246 patients reported LTBI across all treatment groups. of these, 175 with confirmed lab data received INH. Table 1 represents changes in ALT. Percentage of patients with ALT ≥ 1XULN was higher in INH‐treated patients across all treatment groups. No BARI/ADA patients using INH had study treatment interruption due to abnormal hepatic tests. (2).

HBV:

of 2890 patients, 269 had baseline serology suggestive of prior infection (HBcAb+/HBsAb+, n = 255; HBcAb+/HBsAb‐, n = 14; Figure 1). of these, 32 BARI‐treated patients (32/269; 11.9%) later (post‐baseline) tested with HBV DNA+. Out of 32 patients, 8 patients had results above the lower limit of quantitation (LLQ); subsequent tests were either not detectable or below LLQ. No patients developed clinical evidence of hepatitis; ALT tests were within normal range. Conclusion: Data do not suggest an increased hepatic safety risk in patients treated with BARI and concomitant INH. Although some BARI‐treated patients had post‐baseline detectable HBV DNA, none developed clinical evidence of hepatitis. (Table Presented).