Background/Purpose: Although treatment with csDMARDs and bDMARDs can lead to remission in patients with RA, many patients still experience pain and morning (AM) stiffness, which have a meaningful negative impact on quality of life. We assessed the effect of upadacitinib (UPA), a selective JAK-1 inhibitor, alone or in combination with csDMARDs vs background therapy on pain and AM stiffness in patients with active RA who had an inadequate response (IR) to csDMARDs or bDMARDs.

Methods: Data from the SELECT-NEXT (NCT02675426), SELECT-BEYOND (NCT02706847), and SELECT-MONO (NCT02706951) randomized controlled trials were analyzed. Patients in NEXT (csDMARD-IR) and BEYOND (bDMARD-IR) received UPA (15 mg or 30 mg daily) or PBO with csDMARDs for 12 weeks (wks), and those in the MONO trial (csDMARD-IR) received UPA monotherapy (15 mg or 30 mg daily) or MTX (mean dose: 17 mg/wk) for 14 wks. Pain and duration of AM stiffness were assessed through 12/14 wks. Least squares mean (LSM) percent changes from baseline (BL) to wk 12/14 were based on mixed effect repeated measures models. Percentages of patients reporting ≥50% improvement in pain, those reporting no pain or mild pain (absolute pain score <20), and those reporting AM stiffness <15 minutes were determined at each timepoint for UPA (both doses), PBO, or MTX; comparisons between groups used Cochran-Mantel-Haenszel tests with prior bDMARDs use as stratification factor.

Results: Across all 3 trials, statistically significant LSM percent changes from BL to wks 12/14 in pain and duration of AM stiffness were reported in both UPA dose groups (except AM stiffness duration in BEYOND) compared with PBO or MTX groups (Figures 1 and 2). Across trials, significantly (p<0.05) more UPA-treated patients (15 mg: 41–51%, 30 mg: 42–56%) reported ≥50% improvement in pain at wks 12/14 compared with PBO or MTX (19–25%). Significantly (p<0.05) more UPA-treated patients (15 mg: 30-36%, 30 mg: 36-44%) reported no pain or mild pain at wks 12/14 compared with PBO or MTX (14–15%). The percentage of UPA-treated patients (15 mg: 26–42%, 30 mg: 29–43%) reporting AM stiffness duration <15 minutes at wks 12/14 was approximately twice that in PBO or MTX (15–23%) groups. Across all measures, improvements in UPA-treated patients were evident as early as wk 2.

Conclusion: Treatment with UPA in combination with csDMARDs vs PBO resulted in significant and rapid improvements in pain and AM stiffness across different RA patient populations including csDMARD-IR and bDMARD-IR. Similar improvements vs MTX were reported when UPA was administered as monotherapy.

Medical writing services provided by Joann Hettasch (Fishawack Group, US) and funded by AbbVie.