THU0075 EARLY VERSUS DELAYED START OF BARICITINIB IN PATIENTS WITH RHEUMATOID ARTHRITIS IN A PHASE 3 TRIAL OF PATIENTS NAÏVE TO METHOTREXATE TREATMENT

Abstract

Background Baricitinib (bari) is an oral Janus kinase (JAK)1/JAK2 inhibitor approved to treat moderately to severely active rheumatoid arthritis (RA) in adults in over 50 countries including European countries, the US and Japan. In the 52-week (wk) Phase 3 RA-BEGIN study, bari 4-mg alone or in combination with methotrexate (MTX) showed clinical improvements compared to MTX monotherapy for MTX-naive patients (pts) with early active RA.1 Objectives To assess if pts who receive bari monotherapy early attain enhanced clinical, functional and radiographic outcomes compared to pts who initiated MTX and switched to bari at wk 52. Methods In RA-BEGIN, 588 pts (mean disease duration 1.4 years) were randomized 4:3:4 to MTX, bari 4-mg once-daily, or combination MTX and bari 4-mg. At Wk 52, pts could enter a long-term extension study in which all pts received open-label bari 4-mg. Pts initially randomized to bari-4 mg monotherapy were defined as early-start and MTX pts who switched to bari 4-mg at Wk 52 were defined as delayed-start for this analysis. Change from baseline using mixed model repeated measures and mean scores were assessed for the Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), Disease Activity Score 28-joints–high-sensitivity C-reactive protein (DAS28-hsCRP), Disease Activity Score 28-joints–erythrocyte sedimentation rate (DAS28-ESR), Health Assessment Questionnaire-Disability Index (HAQ-DI), and modified Total Sharp Score (mTSS) to compare early- vs delayed-start groups between Wks 0 and 100 (Wks 52-100 for mTSS). Percent of pts achieving low disease activity (LDA, SDAI ≤11) and remission (SDAI ≤3.3) were also assessed. Results LDA and remission response rates in the delayed-start group increased from 60% to 78% and 18% to 31%, respectively, within 4 wks after switching to bari 4-mg. Remission rates reached 47% within 1 year after switching, but were not different from the group that initiated bari (Figure 1). Similar results were seen for CDAI, DAS28-ESR, and DAS28-hsCRP (only up to Wk 40 for DAS28-ESR) (data not shown). Pts initially randomized to bari 4-mg had significantly greater change from baseline, observed as early as Wk 1 and up to Wk 52, for HAQ-DI than pts treated with MTX (Figure 2). After switching to bari, the delayed-start group showed a rapid improvement in HAQ-DI with similar improvement at Wk 56 – 4 wks after switching to bari. Upon initiating bari, there was a reduction in the rate of structural damage; however, delaying initiation of bari for 1 year resulted in numerically higher mTSS. Conclusion In early MTX-naive pts, improved clinical, functional, and radiographic efficacy with bari 4-mg vs MTX was observed in most outcome measures up to 52 wks. Switching from MTX to bari at Wk 52 provided a rapid clinical response, allowing the majority of pts to achieve similar results 4 wks post-switch. However, if the goal of therapy is to achieve rapid and sustained control of disease activity, the differences noted here for HAQ-DI and especially structural progression support earlier switch to bari for pts who do not obtain disease control with MTX. Further analysis may be needed to explore prognostic factors, such as hsCRP and disease duration ( 6 months), baseline erosion, or anti-citrullinated protein antibody positivity, which may help clinicians identify pts who may benefit from earlier treatment with bari.