OP0228 Baricitinib Dose Step-Down Following Disease Control in Patients with Rheumatoid Arthritis:

Abstract

BackgroundPh3 studies demonstrated clinical efficacy of 2 different once-daily (QD) doses of baricitinib (bari) (2mg and 4mg) in patients (pts) with active rheumatoid arthritis (RA) and an inadequate response (IR) to conventional synthetic DMARDs1 or biologic DMARDs2. In general, larger, more rapid and more consistent treatment effects were observed for the 4mg dose across measures.ObjectivesTo investigate the effects of bari dose step-down in patients who had achieved sustained low disease activity (LDA) or remission with bari 4mg QD.MethodsPts who completed a bari Ph3 Study (RA-BEGIN, RA-BEAM, RA-BUILD, or RA-BEACON) could enter a long-term extension study, RA-BEYOND. In RA-BEYOND, pts who had received bari 4mg for at least 15 months and who had achieved sustained LDA or remission (defined by CDAI score at 2 consecutive visits at least 3 months apart) were re-randomized in a double blind manner to continue receiving bari 4mg or to step down to a 2mg QD dose. Disease activity was assessed at a 12 week (wk) landmark following re-randomization.ResultsAmong pts who achieved satisfactory and sustained disease control with bari 4mg QD, randomized, double blind dose reduction to 2mg QD was associated with modest, statistically significant increases in disease activity across measures at a subsequent 12 wk landmark assessment (Table). However, a large majority of pts (in both the continued 4mg and reduced to 2mg groups) retained the state of LDA or remission that led to their re-randomization.RA-BEAM, RA-BUILD, RA-BEACON combinedEfficacy measure†Continued bari 4 mgStepped down to bari 2 mgWk12(N=147)(N=146)CDAI LDA ≤10§, n (%)136 (92.5)123 (84.2)*CDAI remission ≤2.8§, n (%)57 (38.8)54 (37.0)ΔCDAI0.60 (3.44)2.04 (6.29)*ΔTJC 680.3 (3.0)1.2 (3.8)*ΔSJC 660.1 (1.7)0.8 (2.7)*ΔHAQ-DI0.04 (0.26)0.06 (0.28)ΔPain0.7 (14.7)2.5 (16.4)ΔPtGA1.2 (14.3)2.5 (14.5)ΔPhGA−0.0 (9.6)2.7 (13.6)*ΔCRP0.68 (7.16)1.68 (7.82)ΔDAS28-CRP0.14 (0.70)0.36 (0.77)*ΔDAS28-ESR0.10 (0.73)0.35 (0.89)*ΔSDAI0.69 (3.55)2.19 (6.33)*†Values other than CDAI LDA or remission are mean change from baseline (SD) with missing data imputed using modified last observation carried forward; §Missing data imputed using nonresponder imputation; RA-BEAM = MTX-IR pts; RA-BUILD = csDMARD-IR pts; RA-BEACON = bDMARD-IR pts; Δ = change from baseline; CDAI = Clinical Disease Activity Index; CRP = C-reactive protein; DAS28 = Disease Activity Score modified to include the 28 diarthrodial joint count; ESR = erythrocyte sedimentation rate; HAQ-DI = Health Assessment Questionnaire-Disability Index; PhGA = Physician's Global Assessment of Disease Activity; PtGA = Patient's Global Assessment of Disease Activity; SD = standard deviation; SDAI=Simplified Disease Activity Index; SJC = swollen joint count based on 66 joints; TJC = tender joint count based on 68 joints; *p≤0.05 vs. bari 4 mg.ConclusionsConsistent with completed studies, these data indicate that 4mg QD was the most efficacious dose of bari for pts with RA in clinical studies. Most pts who had achieved sustained disease control ...

Clinical efficacy of launched JAK inhibitors in rheumatoid arthritis

“…The long-term safety and tolerability study, RA-BEYOND, which is ongoing at the time of writing, included people with moderate or severe RA who took part in a separate phase IIb study or one of the four trials described above. In this study, those who received baricitinib 4 mg once daily for at least 15 months and who achieved sustained low disease activity or remission (defined by CDAI score at two consecutive visits at least 3 months apart) were re-randomized in a double-blind manner to continue receiving baricitinib 4 mg once daily or to step down to 2 mg daily with or without csDMARDs [34]. Disease activity was assessed at 12 weeks.…”

Baricitinib in rheumatoid arthritis: evidence-to-date and clinical potential

“…Patients who completed RA-BUILD, RA-BEGIN or RA-BEAM were eligible to complete a long-term extension study called RA-BEYOND. 16 In this study, those who received baricitinib 4 mg once daily for at least 15 months and who achieved sustained low disease activity or remission (defined by CDAI score at two consecutive visits at least 3 months apart) were rerandomized in a double blind manner to continue receiving baricitinib 4 mg once daily or to step down to a 2 mg daily dose. Disease activity was assessed at 12 weeks.…”