Dose reduction of baricitinib in patients with rheumatoid arthritis achieving sustained disease control: Results of a prospective study

Background: In patients with rheumatoid arthritis (RA) and inadequate response (IR) to DMARDs, ph3 studies demonstrated efficacy of baricitinib (Bari) (2-mg and 4-mg). Objectives: To investigate the effects of Bari dose step-down in patients who achieved sustained disease control with Bari 4-mg. Methods: Patients with RA participating in the Bari ph3 long-term extension study who received Bari 4-mg for ≥15 months and who achieved sustained low disease activity ([LDA] -CDAI score ≤10) or remission ([REM] -CDAI ≤2.8) ≥3 months apart were re-randomised in a blinded manner to continue Bari 4-mg or step down to 2-mg. Patients could rescue to Bari 4-mg. Efficacy and safety were assessed through 48 weeks (wks) following re-randomisation. (Table Presented) Efficacy and safety data are n/N (%), and n [EAIR], respectively. RABEAM= MTX-IR patients; RA-BUILD=csDMARD-IR patients; RA-BEACON=bDMARD-IR patients; EAIR=exposure-adjusted incidence rate; NRI=nonresponder imputation; SDEAE=step-down emergent adverse event; ∗ p≤0.05, ∗∗ p≤0.01, ∗∗∗ p≤0.001 vs. continued Bari 4-mg Results: The majority of patients in both groups maintained the state of LDA or REM over the 48 wks. However, dose reduction to 2-mg resulted in significant increases in disease activity at 12, 24, and 48 wks (Table). Dose reduction also resulted in a shorter time to relapse (defined as loss of step-down eligibility criteria); significantly more patients relapsed over 48 wks compared to the 4-mg group (figure 1). Rescue rates were 8.3% for Bari 4-mg, 16.6% for Bari 2-mg. Most rescued patients could regain LDA or REM. Dose reduction was associated with a lower rate of infections; rates of SAEs and AEs leading to discontinuation were similar across groups. Conclusions: These data indicate that disease control was better maintained with Bari 4-mg than 2-mg. However, most stepped-down patients could maintain LDA or REM, or recapture control with re-introduction of the 4-mg dose. Stepping down to a dose of 2-mg daily may be a viable option for many patients who have achieved sustained LDA or REM on the 4-mg dose.