Response to baricitinib at 4 weeks predicts response at 12 and 24 weeks in patients with rheumatoid arthritis: Results from two phase 3 studies

Background: Baricitinib (bari), a JAK1 and JAK2 inhibitor, showed significant improvements across multiple measures of disease activity as early as week (wk) 1 that were maintained through wk 52 in ph 3 studies of patients (pts) with active RA.1,2 Objectives: To determine if, in bari-treated pts, early changes in disease activity predicted later achievement of low disease activity (LDA) or remission. Methods: 1305 pts with inadequate response to methotrexate (MTX) were randomized in RA-BEAM (3:3:2, oral PBO/4 mg bari QD/SC injection adalimumab [ADA] Q2W, 52 wks); 584 MTX-naïve pts were randomized in RA-BEGIN (4:3:4, oral MTX QW/4 mg bari QD/4 mg bari QD+MTX QW, 52 wks). Improvement from baseline (BL) to wk 4 was used to predict LDA or remission defined by Disease Activity Score (DAS28) and Simplified Disease Activity Index (SDAI) at wks 12/24 (bari 4 mg arm, both studies). Early responder and early nonresponder were predefined as Clinical Disease Activity Index (CDAI) improvement ≥6 and <6, respectively, at wk 4. Results: Compared to PBO or ADA (RA-BEAM) or MTX (RA-BEGIN), treatment with bari was associated with rapid decrease in DAS28 and CDAI from wk 1.1,2 By wk 4, 86% (RA-BEAM) and 85% (RA-BEGIN) of bari pts had a CDAI decrease ≥6. In both studies, LDA/remission rates at wks 12/24 were higher in pts with CDAI improvement ≥6 compared to pts with CDAI improvement <6 from BL to wk 4 (Table). Negative predictive values (NPV) for remission at wks 12/24 associated with CDAI improvement <6 from BL to wk 4 exceeded 90%, indicating that pts with CDAI improvement <6 were highly unlikely to achieve remission; NPV for LDA exceeded 80%. Conclusions: In RA-BEAM/RA-BEGIN, lack of early clinical response to bari 4 mg (failure to achieve CDAI improvement ≥6 at 4 wks) was associated with low rates of LDA/remission at wks 12/24. These results are consistent with similar analyses from previous ph 3 studies of bari.3 The majority of bari pts had improvement in CDAI ≥6 at wk 4; these decreases were associated with improved clinical responses at wks 12/24. Early identification of pts (4 wks) who are not likely to achieve LDA/remission may be useful in tailoring therapy to individual pts. (Table Presented).