Background/Purpose: Baricitinib (bari), an oral selective JAK1 and JAK2 inhibitor, has been shown to be safe and efficacious compared to placebo (PBO) in two Phase 3 trials in patients (pts) with moderate to severe RA and an inadequate response (IR) to conventional DMARDs (cDMARDs).^1,2 The objective of this analysis was to evaluate efficacy and safety of bari 4 mg vs. PBO in the United States (US) vs. the “rest of world” (ROW) subpopulations of these two studies.

Methods: Eligibility requirements included ≥6 swollen and tender joints and no prior biologic DMARD use. In RA-BUILD, cDMARD-IR pts with hsCRP≥3.6 mg/L were randomized to PBO or bari (2 or 4 mg) once daily (QD).¹ In RA-BEAM, MTX-IR pts with x-ray erosions and hsCRP≥6.0 mg/L were randomized to PBO QD, bari 4 mg QD, or adalimumab 40 mg biweekly.² Primary endpoint in both trials was ACR20 at Wk 12 for bari 4 mg vs. PBO. This post-hoc analysis combined data from both trials providing overall samples for bari 4 mg (N=714) and PBO (N=716). The geographically-defined subpopulations were US/Puerto Rico [US/PR] and ROW. Descriptive statistics were utilized for efficacy and safety analyses.

Results: There were 188 US/PR and 1,242 ROW pts in this analysis. The proportions of pts who were White or Black/African-American were higher in US/PR; Asians were more represented in ROW. US/PR pts were slightly older, with fewer years of RA, and a lower percentage were RF/ACPA positive or used corticosteroids. More US/PR pts had previously used 1 cDMARD and more ROW had previously used ≥3cDMARDs (Table 1). Bari 4 mg demonstrated better responses vs. PBO across US/PR and ROW for multiple efficacy outcomes, including ACR20/50/70, LDA, remission, DAS28-CRP, and HAQ-DI (Table 2). Comparing US/PR and ROW efficacy, no systematic differences were observed. No significant safety differences were identified for US/PR or ROW pts at Wk 12 for bari 4 mg vs. PBO in the incidence of ≥1 adverse event (AE), serious AE, or discontinuation due to AE or death (Table 3). There was 1 death in PBO in each subpopulation.

Conclusion: In this post-hoc, pooled analysis from two Phase 3 trials in cDMARD-IR patients, bari 4 mg demonstrated efficacy compared to PBO in US/PR patients. References: ¹Dougados M et al. Ann Rheum Dis 2015;74(S2):79; ²Taylor P et al. Arthritis Rheumatol 2015;67(suppl 10):3928.