Journal Article

SAT0244 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

Dore, R., Chen, K., Shaw, T., Suboticki, J. L., Hall, S., van Vollenhoven, R., Enejosa, J., Camp, H. S.

2018

Overview

Background: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 Objectives:To assess the impact of UPA at 12 wks on individual and composite measures of RA disease activity.Methods:Pts received UPA 15 mg or 30 mg 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 pts, 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% improvement 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 15 mg and 30 mg 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.Conclusions: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., Arthritis Rheumatol2017;69:S10.[2]Genovese, et al. Arthritis Rheumatol2017;69:S10.[3]Smolen, et al. 2015. doi:10.1136/annrheumdis-2015-207524Acknowledgements:AbbVie Inc was the study sponsor, contributed to study design, data collection, analysis & interpretation, and to writing, reviewing, and approval of final version. Medical writing support was provided by Naina Barretto, PhD, of AbbVie, Inc.Disclosure of Interest:R. van Vollenhoven Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, Roche, and UCB, Consultant for: AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, Crescendo, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, UCB, and Vertex, Speakers bureau: AbbVie, AstraZeneca, Biotest, Bristol-Myers Squibb, Celgene, Crescendo, GlaxoSmithKline, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, UCB, and Vertex, R. Dore: None declared, K. Chen Shareholder of: AbbVie, Employee of: AbbVie, H. Camp Shareholder of: AbbVie, Employee of: AbbVie, J. Enejosa Shareholder of: AbbVie, Employee of: AbbVie, T. Shaw Shareholder of: AbbVie, Employee of: AbbVie, J. Suboticki Shareholder of: AbbVie, Employee of: AbbVie, S. Hall: None declared

• Publisher: Elsevier Limited
• Subject: C-reactive protein / Clinical trials / Data processing / Janus kinase / Pain / Patients / Rheumatoid arthritis / Stockholders