Background/Purpose: Baricitinib (bari), an oral selective Janus kinase 1/2 inhibitor, has shown clinical efficacy in patients (pts) with RA and an inadequate response to conventional synthetic DMARDs.¹ Baricitinib is approved for treating moderate-severe RA in over 40 countries. The two objectives of these analyses were to evaluate the percentage of pts, originally randomized to 2 mg or 4 mg in the Phase 3 RA-BUILD study, and rescued in the study and/or in RA-BEYOND (the long-term extension study); and to assess the clinical benefits post-rescue.

Methods: RA-BUILD was a 24-week study evaluating once daily bari 4 mg (N=227) and 2 mg (N=229) compared to placebo (N=228). Pts with <20% improvement in tender joint count or swollen joint count (SJC) at Weeks 14 and 16 compared to baseline were rescued to bari 4 mg at Week 16; at Week 20, rescue was based on investigators’ decision. Pts not rescued continued blinded treatment in RA-BEYOND and those with Clinical Disease Activity Index (CDAI)>10 at or after 3 months in RE-BEYOND were eligible for rescue to bari 4 mg, but not required. Once rescued, change in background medications was allowed. In RA-BEYOND, unrescued pts achieving sustained CDAI ≤10 were randomized to bari 2 mg or maintained at 4 mg. Descriptive longitudinal data analysis was based on observed data from pts randomized to bari 2- or 4-mg in RA-BUILD, including data up to 1 April 2017 in RA-BEYOND. Percent rescued and overall response rates in achieving CDAI ≤10, and pain (visual analogue scale ≤10, 20 or 40 mm), were evaluated from time of original randomization to bari 4 mg and 2 mg in RA-BUILD. Median change over time in CDAI, HAQ, SJC28 and pain after rescue from 2 to 4 mg was evaluated using pt data at time of rescue (reset as Week 0).  

Results: The percentage of pts on bari 4 mg “rescued” in RA-BUILD was 36% compared to 52% in pts originally assigned to bari 2 mg. In RA-BEYOND, 7% of pts originally randomized to 4 mg were rescued after dose tapering to 2 mg. Clinically meaningful response rates in CDAI (≤10) and pain improvement increased and stabilized over time in the bari-treated population. Pts rescued in RA-BEYOND, after being treated with bari in RA-BUILD had less disease activity compared to pts rescued in RA-BUILD at the time of rescue (Table). Pts on 2 mg rescued to bari 4 mg in RA-BEYOND demonstrated improved disease control with the majority achieving CDAI≤10 and pain reduction (Figure).

Conclusion: Fewer pts originally assigned to bari 4 mg in RA-BUILD required rescue compared to pts assigned to 2 mg. Disease activity assessed by CDAI and patient-reported pain improved in many pts after rescue from 2 to 4 mg of bari.

References: 1.Dougados, M et al. Ann Rheum Dis. 2017;76:88