Predictors for Achievement of Low Disease Activity at Week 56 in Patients with Psoriatic Arthritis Who Received Upadacitinib 15 Mg Once Daily: Pooled Analysis of Two Phase 3 Studies

BackgroundUpadacitinib (UPA) 15 mg once daily (QD) has demonstrated efficacy and safety in patients with psoriatic arthritis (PsA) for up to 56 weeks in the Phase 3 SELECT-PsA 1 and 2 trials.1,2ObjectivesThis post hoc analysis of these studies explored the association of baseline characteristics and short-term responses with achievement of minimal disease activity (MDA) and Disease Activity Index for Psoriatic Arthritis (DAPSA) low disease activity (LDA).MethodsData were pooled from patients with prior inadequate response or intolerance to ≥1 non-biologic (b) DMARDs (SELECT-PsA 1) or ≥1 bDMARDs (SELECT-PsA 2) originally randomized to UPA 15 mg QD. Logistic regression models were used to assess the association between baseline characteristics and short-term (Week 12) responses with achieving MDA or DAPSA LDA at 56 weeks, sustained MDA (MDA at Weeks 36 and 56), or sustained DAPSA LDA (DAPSA LDA at Weeks 36, 44, and 56). Each predictor was evaluated separately in an initial model that included effects for study and concurrent non-bDMARD use. Odds ratios and concordance (c-)statistics were used to determine the predictive accuracy. Statistically significant predictors were then evaluated simultaneously using stepwise logistic regression with the Akaike Information Criterion for model-building.ResultsOf 640 patients included in the analysis, 40% and 47% achieved MDA and DAPSA LDA, respectively, at 56 weeks. Evaluated separately, younger age, sex (male), geographic region, lower weight, lower body mass index, the presence of dactylitis or enthesitis, and lower scores of Patient’s Assessment of Pain (Pt-Pain), Patient’s Global Assessment (PtGA), tender joint count in 68 joints, and Health Assessment Questionnaire-Disability Index (HAQ-DI) were significant baseline predictors for achieving MDA and DAPSA LDA at Week 56. Lower Pt-Pain (Weeks 12–24) and PtGA (Weeks 16–24) scores were strongly predictive (c-statistics >0.8) of achieving MDA at Week 56, and both measures (from Week 8) were moderately predictive (c-statistics >0.7) of achieving DAPSA LDA. Evaluated simultaneously with several baseline characteristics, lower Pt-Pain and HAQ-DI scores at Week 12 were included in models strongly predictive of achieving MDA (c-statistic=0.850; Figure 1) and DAPSA LDA (c-statistic=0.840; Figure 2) at Week 56. For each 1-point increase in Pt-Pain or HAQ-DI scores at Week 12 (after adjusting for other effects in the model), patients were less likely to achieve MDA (by 32% or 56%, respectively) or DAPSA LDA (by 23% or 31%, respectively) at Week 56. Predictors for achieving sustained MDA and sustained DAPSA LDA were generally similar to those identified for achieving MDA and DAPSA LDA, respectively.ConclusionIn patients with PsA receiving UPA 15 mg, baseline characteristics and early responses strongly predicted achievement of MDA or DAPSA LDA at Week 56. This may guide considerations of treatment targets in clinical trials and encourage physicians to further optimize treatment of their patients in clinical practice.References[1]McInnes IB, et al. Ann Rheum Dis 2020;79:16–7.[2]Mease PJ, et al. Rheumatol Ther 2021 [Epub ahead of print].AcknowledgementsAbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, review, and approval of the abstract. No honoraria or payments were made for authorship. Medical writing support was provided by Hilary Wong, PhD, of 2 the Nth (Cheshire, UK), which was funded by AbbVie.Disclosure of InterestsDaniel Aletaha Consultant of: AbbVie, Grünenthal, Janssen, Medac, Merck, Mitsubishi/Tanabe, Pfizer, Roche, and UCB, Grant/research support from: AbbVie, Grünenthal, Janssen, Medac, Merck, Mitsubishi/Tanabe, Pfizer, Roche, and UCB, Philip J Mease Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, and Janssen, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Genentech, Gilead, and Janssen, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, and Janssen, Ralph Lippe Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Frank Behrens Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Chugai, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Chugai, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, and UCB, Grant/research support from: Chugai, GlaxoSmithKline, Janssen, Pfizer, and Roche, Derek Haaland Speakers bureau: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, Takeda, and UCB, Consultant of: AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, Takeda, and UCB, Grant/research support from: AbbVie, Adiga Life Sciences, Amgen, Bristol-Myers Squibb, Can-Fite BioPharma, Celgene, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Regeneron, Sanofi, and UCB, Penelope Palominos Speakers bureau: AbbVie, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Janssen, Novartis, Pfizer, and UCB, Apinya Lertratanakul Shareholder of: formerly of AbbVie, Employee of: former employee of AbbVie, Michael Lane Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Kevin Douglas Shareholder of: AbbVie Inc., Employee of: AbbVie Inc., Peter Nash Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, and UCB, Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Merck, Novartis, Pfizer, Roche, Sanofi, and UCB, Arthur Kavanaugh Speakers bureau: AbbVie, Amgen, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Janssen, Novartis, Pfizer, and UCB