Background/Purpose:

Upadacitinib (UPA), an oral, JAK1-selective inhibitor, demonstrated efficacy through 12 and 24 weeks (wks) in phase 3 trials of patients (pts) with active rheumatoid arthritis (RA) and inadequate response (IR) to csDMARDs and bDMARDs, respectively.^1,2 Efficacy evaluations at Wk 12 are an important assessment point according to T2T recommendations.³ The purpose of this analysis was to assess the impact of UPA at 12 wks on individual and composite measures of RA disease activity.

Methods: Pts received UPA 15mg or 30mg once daily (QD) or PBO for 12 wks in two phase 3 trials. SELECT NEXT¹ and SELECT BEYOND² enrolled csDMARD- and bDMARD-IR pts, respectively. For this investigation, responses at Wk 12, were defined as ≥50% improvement in ACR components. Among ACR50 responders, the proportions of pts achieving ≥50% improvement in all 7 components of the ACR response criteria [Tender Joint Count (TJC68), Swollen Joint Count (SJC66), Pt Global Assessment (PtGA), Physician Global Assessment (PhGA), Pt Pain, Health Assessment Questionnaire-Disability Index (HAQ-DI), and high sensitive C-reactive protein (hsCRP)] were assessed. Differences in the cumulative distributions of CDAI, DAS28-CRP, and SDAI between baseline (BL) and Wk 12 were assessed. All analyses were based on observed data without imputation.

Results: Pts in both studies, on average, had established, moderate to severe RA at BL, with (mean) disease durations of 7.3 and 13.2 years, CDAI of 38.2 and 40.9, in csDMARD-IR and bDMARD-IR, respectively; 53% of bDMARD-IR pts had exposure to ≥2 bDMARDs.^1,2 In both populations, significantly more pts on UPA vs PBO achieved ≥50% improvements in each ACR component at Wk 12 (Table). Among pts who achieved ACR50 at Wk 12, approximately one-half of the csDMARD-IR and one-third of the bDMARD-IR pts achieved ≥50% improvement in all 7 ACR components. While there were no differences at BL, cumulative distributions of CDAI, DAS28-CRP, and SDAI separated by treatment at Wk 12 (p<0.001); for the lowest quartiles for UPA 15mg and 30mg vs PBO, CDAI levels dropped to 6.2 and 5.1 vs 12.5 in csDMARD-IR; and 7.2 and 8.2 vs 13.1 in bDMARD-IR.

Conclusion:

In pts with an insufficient response to either csDMARDs or bDMARDs, treatment responses at 12 wks were observed in significantly higher proportions with UPA vs PBO. Favorable effects with UPA were seen in the composite scores and the individual parameters, including PROs and acute-phase reactants.

References:

1. Burmester et al; 2017, Arthritis Rheumatol;69 S10
2. Genovese et al; 2017, Arthritis Rheumatol;69 S10
3. Smolen et al; 2015;doi:10.1136/annrheumdis-2015-207524

« Back to 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/impact-of-12-weeks-of-upadacitinib-treatment-on-individual-and-composite-disease-measures-in-patients-with-rheumatoid-arthritis-and-inadequate-response-to-conventional-synthetic-or-biologic-dmards/