Background: Baricitinib (Bari) is an oral Janus Kinase (JAK)1/JAK2 inhibitor in development for patients with active rheumatoid arthritis (RA). In Phase 3 studies, Bari has demonstrated clinical efficacy and has a favorable safety profile.

Objectives: To evaluate Bari 2- and 4-mg in patients who have failed multiple DMARDs, across several studies.

Methods: Data from the subgroup of patients who had failed ≥2 DMARDs, including approx. one-half of patients in RA-BUILD (csDMARD-IR) and RA-BEAM (MTX-IR) and all patients from RA-BEACON (bDMARD-IR) were assessed, post hoc, for comparison of Bari 2-mg and 4-mg to placebo across time points using the following measures: ACR20, ACR50, ACR70, SDAI, CDAI, DAS28-CRP, HAQ-DI, and radiographic assessment of structural damage (mTSS), as well as safety. For patients who had failed ≥2 DMARDs from RA-BEAM, a comparison was also made between Bari 4-mg and adalimumab.

Results: In the ≥2 DMARD-IR populations from RA-BEACON, RA-BUILD, and RA-BEAM, >95% had failed MTX as one of the DMARDs. Compared to PBO in this population, Bari resulted in statistically significantly greater improvement in efficacy measures at Week 24, including physical function (Table). In the ≥2 DMARD-IR population from RA-BEAM (all patients received background MTX), Bari 4-mg was associated with greater improvements compared to adalimumab (table 1 and figure 1). Compared to PBO, Bari 4-mg statistically significantly inhibited structural progression at Week 24 in the ≥2 DMARD-IR subsets of RA-BEAM and RA-BUILD. The overall safety profile of Bari 4-mg in the ≥2 DMARD-IR population was consistent with findings from the overall baricitinib-treated population.

^¥Data are the proportion (%) of pts who achieved the response at Week 24 (nonresponder imputation), unless otherwise indicated. ^§Approximately 56% of patients in RA-BUILD and 54% of patients in RA-BEAM failed ≥2 DMARDs. Δ=least squares mean change from baseline (modified last observation carried forward). ^¶mTSS data are as randomized using last observation carried forward. *p≤0.05, **p≤0.01, ***p≤0.001 for Bari 4-mg or Bari 2-mg vs. PBO; ^‡p≤0.05 Bari 4-mg vs. ADA

Conclusions: These data demonstrate that a dose response is present between Bari 2-mg and Bari 4-mg, with both doses providing benefit in the patients who failed multiple DMARDs in the phase 3 program by improving signs and symptoms, physical function, and structure.

Disclosure of Interest: M. Genovese Grant/research support from: Eli Lilly & Company, AbbVie, Consultant for: Eli Lilly & Company, AbbVie, M. Dougados Grant/research support from: Abbvie, Pfizer, Eli Lilly and Company, Novartis, UCB, Merck, Roche, BMS, Consultant for: Abbvie, Pfizer, Eli Lilly and Company, Novartis, UCB, Merck, Roche, BMS, S. Schwartzman Shareholder of: Amgen, Boston Scientific, Gilead, Medtronic, Consultant for: Abbvie, Crescendo, Dermtech, Genentech, Gilead, Janssen, Eli Lilly and Company, Novartis, Pfizer, Regeneron, Sanofi, UCB, Speakers bureau: Abbvie, Genentech, Janssen, Eli Lilly and Company, Novartis, Pfizer, Regeneron, Sanofi, UCB, Genentech, D. Schlichting Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, S. Beattie Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, L. Xie Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, A. Cardoso Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, J. Smolen Grant/research support from: AbbVie, Janssen, Eli Lilly and Company, MSD, Pfizer, Roche, Consultant for: AbbVie, Amgen, Astra-Zeneca, Astro, BMS, Celgene, Celltrion, Chugai, Gilead Glaxo, ILTOO, Janssen, Eli Lilly and Company, Medimmune, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi-Aventis, UCB