Background Baricitinib (BARI) is an oral selective Janus kinase (JAK 1/2)1 inhibitor approved in the EU, Japan, and other countries for treatment (tx) of moderately to severely active rheumatoid arthritis (RA) in adults. RA therapies may increase risk of tuberculosis (TB).2 The use of isoniazid (INH) plays a vital role to control TB. However, INH may result in hepatic adverse events (AEs)3. Limited data exist on hepatic safety in TB patients (pts) with RA treated with JAK inhibitors and INH.
Objectives To evaluate the hepatic safety in pts with RA, who were receiving INH for latent TB (LTBI) in BARI phase 3 trials.
Methods This is a descriptive post-hoc analysis of three phase 3 studies: RA-BEAM, RA-BUILD, and RA-BEACON. All pts were screened for LTBI prior to randomisation. Pts with untreated LTBI and without documentation of prior completed tx, received INH at least for 4 weeks (wk) prior to randomisation and during the clinical trial period. Changes in ALT levels (≥1X,≥3X,≥5X, and ≥10X of ULN) from baseline up to 24 wk were analysed by tx groups (BARI 4 mg, BARI 2 mg, adalimumab [ADA], and placebo [PBO]).
Results In total, 2516 pts were included in this analysis. Of these, 891 pts were treated with BARI 4 mg, 403 with BARI 2 mg, 330 with ADA, and 892 with PBO. Background csDMARDs, mainly methotrexate (MTX) were continued. Overall, 246 pts reported LTBI at screening across all tx groups. Of these, 169 with confirmed lab data received INH as LTBI tx. At wk 24, ALT≥1X was reported in 24 (41.4%) pts receiving BARI 4-mg+INH. None of the pts in BARI 4-mg+INH reported ALT level of ≥3X,≥5X, and ≥10X ULN. For BARI 2-mg+INH, ALT≥1X reported in 9 (33.3%) pts, ALT≥3X in 2 (7.4%), ALT≥5X in 1 (3.7%), and ALT≥10X in 1 (3.7%) of the pts. Among pts treated with ADA +INH, ALT≥1X was reported in 12 (44.4%), ALT≥3X in 2 (7.4%), ALT≥5X in 1 (3.7%), and ALT≥10X in none of pts. Among pts treated with PBO+INH, ALT≥1X was reported in 21 (36.8%), ALT≥3X and ALT≥5X levels were reported in 2 (3.5%, for both) of the pts. None of the pts reported ALT≥10X. One pt receiving INH in RA-BEAM PBO arm had temporary interruption of tx due to abnormal hepatic lab results. No study tx interruption or discontinuation was reported in INH users in BARI or ADA groups due to abnormal hepatic lab results.
Conclusions The percentage of pts with ≥1X ULN ALT was numerically higher in INH group vs no INH and was consistent across PBO, BARI and ADA tx groups. The data do not suggest an increased hepatic safety risk in pts treated with BARI who were receiving concomitant INH.
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Disclosure of Interest T.-Y. Hsieh: None declared, W.-N. Huang: None declared, H.-P. Tony Consultant for: Abbvie, AstraZeneca, Chugai, Janssen Cilag, Eli Lilly and Company, Novartis, Roche, Sandoz Hexal, A. Balsa Grant/research support from: Pfizer, AbbVie, UCB, Roche, Novartis, Consultant for: Pfizer, Novartis, AbbVie, MSD, UCB, Roche, BMS, Novartis, Celltrion, Nordic, K. Winthrop Grant/research support from: Pfizer, BMS, Consultant for: Pfizer, UCB, Abbvie, Eli Lilly and Company, Amgen, BMS, M. Harigai Grant/research support from: BristolMyers Squibb K.K., Eisai Co., Ltd., Ono Pharmaceuticals, and Takeda Pharmaceutical Co., Ltd., Consultant for: Eli Lilly and Company, C. Dickson Employee of: Eli Lilly and Company, W.-S. Wu Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, I. de la Torre Employee of: Eli Lilly and Company, R. Liao Employee of: Eli Lilly and Company, L. Chen Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, S. Kumar Employee of: Eli Lilly and Company, B. Combe Grant/research support from: Pfizer, UCB, Consultant for: Abbvie, BMS, Janssen, Lilly, MSD, Novartis, Pfizer, Roche-Chugai, UCB, Speakers bureau: BMS, Janssen, Lilly, MSD, Pfizer, Roche-Chugai, UCB
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