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

Background: In patients (pts) with active rheumatoid arthritis (RA) and inadequate response (IR) to DMARDs, ph3 studies demonstrated efficacy of baricitinib (bari) (2mg and 4mg). Larger, more rapid treatment effects were observed for bari 4mg. Objectives: To investigate the effects of bari dose step-down in pts who achieved sustained disease control with bari 4mg. Methods: Pts with RA who completed a bari ph3 study could enter a long-term extension (LTE) study. In the LTE, pts who received bari 4mg for ≥15 months and who achieved sustained low disease activity ([LDA]-CDAI score ≤10) or remission (CDAI ≤2.8) at 2 consecutive visits ≥3 months apart were re-randomised in a blinded manner to continue bari 4mg or step down to 2mg. Patients could rescue (to bari 4mg) if CDAI >10. Efficacy and safety were assessed through 48 weeks (wks) following re-randomisation. Results: Among pts who achieved sustained disease control with bari 4mg, dose reduction to 2mg resulted in significant increases in disease activity at 12, 24, and 48 wks; however, the majority of pts in both groups maintained the state of LDA or remission. Rescue rates were 7.3% for bari 4mg, 17.1% for bari 2mg. Most rescued patients could regain LDA or remission. Dose reduction was associated with a lower rate of non-serious infections; rates of SAEs and AEs leading to discontinuation were similar across groups. Conclusions: These data indicate that 4mg once daily was the most efficacious dose of bari for pts with RA; increases in disease activity were consistently seen with dose reduction from 4mg to 2mg in well-controlled pts. However, after step-down most pts could maintain LDA or remission, or recapture control with return to 4mg if needed. Attempted dose taper may be a reasonable consideration for some pts following induction of sustained disease control with bari 4mg.