Background:Approximately 40% of PsA patients (pts) on advanced therapy are on monotherapy.1,2 Upadacitinib (UPA) showed efficacy and safety in pts with active PsA in the Phase 3 SELECT-PsA 1 and SELECT-PsA 2 clinical trials.3,4Objectives:Assess efficacy and safety in subgroups of pts treated with UPA as monotherapy or in combination with non-biologic disease-modifying antirheumatic drugs (non-bDMARDs).Methods:The SELECT-PsA program enrolled pts with prior inadequate response (IR) or intolerance to ≥1 non-bDMARD (N=1705) and prior IR or intolerance to ≥1 bDMARD (N=642). Data from both trials was integrated for pts receiving placebo (PBO), UPA 15 mg once daily (QD) and UPA 30 mg QD. Stable background treatment of ≤2 non-bDMARDs was permitted, but not required. Analysis includes UPA monotherapy vs combination therapy for endpoints: ACR20/50/70 responses and change from baseline in pain and HAQ-DI (Wk 12); Static Investigator Global Assessment of Psoriasis of 0 or 1 and at least a 2-point improvement from baseline and PASI75/90/100 responses (Wk 16); proportion of pts achieving resolution of enthesitis, dactylitis, and minimal disease activity (Wk 24). Binary outcomes, using the Cochran-Mantel-Haenszel-method and continuous outcomes, using mixed-effects model, were analyzed for repeated measures in the subgroups of UPA monotherapy and combination therapy. Point estimates and 95% confidence intervals (CIs) of PBO subtracted treatment effect were calculated. Treatment-emergent adverse events (TEAEs) were analyzed.Results:Of 1916 pts, 574 (30%) received monotherapy and 1342 (70%) received combination therapy; 84% in combination therapy group received MTX +/- another non-bDMARD. Both UPA monotherapy and combination therapy led to improvements in efficacy vs PBO and across endpoints, for each dose, generally consistent point estimates of PBO subtracted treatment effect and associated overlapping CIs were observed (Figure 1). Generally, frequency of AEs and serious AEs, were comparable with UPA administered as monotherapy and combination therapy (Table 1). Frequency of AEs of serious infections and hepatic disorder were lower with monotherapy while frequency of AEs leading to discontinuation of study drug were lower with combination therapy. Most hepatic disorders were transient transaminase elevations.Conclusion:In the SELECT PsA trials, efficacy and safety of UPA was generally consistent when administered as monotherapy or when given in combination with non-bDMARDs. Results from this analysis support the use of UPA with or without concomitant non-bDMARDs.References:[1]Ianculescu I and Weisman MH, Clin Exp Rheumatol 2015; 33:S94–S97.[2]Mease PJ, et al. RMD Open 2015; 1:e0000181.[3]McInnes IB, et al. Ann Rheum Dis, 2020; 79:12.[4]Genovese MC, et al. Ann Rheum Dis, 2020; 79:139.Acknowledgements:AbbVie and the authors thank the patients, study sites, and investigators who participated in this clinical trial. AbbVie, Inc was the study sponsor, contributed to study design, data collection, analysis & interpretation, and to writing, reviewing, and approval of final version. No honoraria or payments were made for authorship. Medical writing support was provided by Ramona Vladea of AbbVie Inc.Disclosure of Interests:Peter Nash Speakers bureau: AbbVie, BMS, Roche, Pfizer, Janssen, Amgen, Sanofi-Aventis, UCB, Eli Lilly, Novartis, and Celgene, Consultant of: AbbVie, BMS, Roche, Pfizer, Janssen, Amgen, Sanofi-Aventis, UCB, Eli Lilly, Novartis, and Celgene, Grant/research support from: AbbVie, BMS, Roche, Pfizer, Janssen, Amgen, Sanofi-Aventis, UCB, Eli Lilly, Novartis, and Celgene, Pascal Richette Speakers bureau: AbbVie, Biogen, Janssen, BMS, Roche, Pfizer, Amgen, Sanofi-Aventis, UCB, Lilly, Novartis, and Celgene, Consultant of: AbbVie, Biogen, Janssen, BMS, Roche, Pfizer, Amgen, Sanofi-Aventis, UCB, Lilly, Novartis, and Celgene, Laure Gossec Speakers bureau: Abbvie, Amgen, Biogen, BMS, Celgene, Lilly, Novartis, Pfizer, Janssen, Sandoz, Sanofi-Aventis, UCB, Consultant of: Abbvie, Amgen, Biogen, BMS, Celgene, Lilly, Novartis, Pfizer, Janssen, Sandoz, Sanofi-Aventis, UCB, Grant/research support from: Abbvie, Amgen, Biogen, BMS, Celgene, Lilly, Novartis, Pfizer, Janssen, Sandoz, Sanofi-Aventis, UCB, Antonio Marchesoni Speakers bureau: AbbVie, BMS, Celgene, Eli-Lilly, Janssen, MSD, Novartis, Pfizer, and UCB, Consultant of: AbbVie, BMS, Celgene, Eli-Lilly, Janssen, MSD, Novartis, Pfizer, and UCB, Christopher T. Ritchlin Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Novartis, UCB, Grant/research support from: UCB, Koji Kato Shareholder of: AbbVie, Employee of: AbbVie, Erin McDearmon-Blondell Shareholder of: AbbVie, Employee of: AbbVie, Elizabeth Lesser Shareholder of: AbbVie, Employee of: AbbVie, Reva McCaskill Shareholder of: AbbVie, Employee of: AbbVie, Dai Feng Shareholder of: AbbVie, Employee of: AbbVie, Jaclyn Anderson Shareholder of: AbbVie, Employee of: AbbVie, Eric Ruderman Consultant of: AbbVie, Amgen, Gilead, Janssen, Lilly, Novartis, and Pfizer.
Assessing Treatment Effect Variation in Observational Studies: Results from a Data Challenge