AB0547 ASSOCIATION BETWEEN ACHIEVEMENT OF LOW DISEASE ACTIVITY OR REMISSION WITH IMPROVEMENT IN QUALITY OF LIFE IN UPADACITINIB-TREATED PATIENTS IN THE PHASE 3 SELECT-PsA 1 AND 2 STUDIES
Authors: A. Kavanaugh, P. J. Mease, K. Douglas, F. Behrens, D. Haaland, P. Palominos, A. Lertratanakul, M. Lane, R. Lippe, D. Aletaha, P. Nash
Journal: Annals of the Rheumatic Diseases (2021)

Background: The efficacy and safety of upadacitinib (UPA) in patients (pts) with active psoriatic arthritis (PsA) was demonstrated in the phase 3 SELECT-PsA 1 and SELECT-PsA 2 clinical trials. 1,2 Objectives: To explore the relationship between achievement of low disease activity (LDA) or remission (REM) and pt-reported outcomes (PROs) in SELECT-PsA 1 and 2. Methods: The SELECT-PsA program enrolled pts with prior inadequate response or intolerance to ≥1 non-biologic disease-modifying antirheumatic drug (DMARD; SELECT-PsA 1) or ≥1 biologic DMARD (SELECT-PsA 2). Pts were randomized to 56 weeks (wks) of blinded treatment with UPA 15 or 30 mg once daily (QD), placebo switched to UPA 15 or 30 mg QD at Wk 24, or adalimumab (SELECT-PsA 1 only) 40 mg every other wk. LDA and REM were evaluated using the minimal disease activity (MDA; fulfillment of 5 out of 7) criteria and the Disease Activity index for Psoriatic Arthritis (DAPSA; cutoff ≤4), respectively. PROs assessed included Health Assessment Questionnaire-Disability Index (HAQ-DI), 36-Item Short-Form Survey physical component summary (SF-36 PCS), 5-Level EuroQol 5-Dimension (EQ-5D-5L) Index, and EQ-5D-5L Visual Analog Scale (VAS). Integrated data through Wk 56 from SELECT-PsA 1 and 2 from the full analysis set with both continuous UPA 15 mg and 30 mg groups were analyzed by responder status at Wks 24 and 56. Changes from baseline (BL) in PROs were analyzed using mixed effects repeated measures models (fixed effects for study, current use of non-biologic DMARDs, treatment group, visit, responder status, and continuous BL PROs). As-observed data were used in the models. Results: A total of 1281 pts were included in the analysis (UPA 15 mg, n=640; UPA 30 mg, n=641). MDA was achieved by 33% (UPA 15 mg) and 40% (UPA 30 mg) of patients at Wk 24, and 40% (UPA 15 mg) and 43% (UPA 30 mg) at Wk 56; and DAPSA-REM by 10% (UPA 15 mg) and 17% (UPA 30 mg) at Wk 24, and 16% (UPA 15 mg) and 18% (UPA 30 mg) at Wk 56. Pts who achieved MDA or DAPSA-REM (responders) at Wk 56 achieved larger reductions in HAQ-DI and larger increases in SF-36 PCS, EQ-5D-5L Index and EQ-5D-5L VAS compared with non-responders (Table 1) (all p&lt;0.0001; statistical significance was exploratory in nature). MDA or DAPSA-REM response at Wk 24 was also associated with greater PRO improvements at Wk 56 (Figure 1). Consistent with the results presented for MDA and DAPSA-REM, patients who achieved Very Low Disease Activity or DAPSA-LDA also experienced greater improvements in PROs than those who did not. Table 1. Change from BL in PROs at Wk 56 by MDA and DAPSA-REM responder status at Wk 56 UPA 15 mg QD (n=640 ) UPA 30 mg QD (n=641 ) Least squares mean change from BL (95% CI), unless stated otherwise Non-responder Responder Non-responder Responder MDA, n a 386 254 368 273 HAQ-DI −0.26 (−0.30, −0.22) −0.61* (−0.66, −0.56) −0.27 (−0.31, −0.23) −0.69* (−0.74, −0.64) SF-36 PCS 5.25 (4.60, 5.90) 12.63* (11.84, 13.41) 5.09 (4.42, 5.75) 13.84* (13.08,14.59) EQ-5D-5L Index 0.11 (0.09, 0.12) 0.25* (0.23, 0.26) 0.10 (0.09, 0.12) 0.27* (0.25, 0.28) EQ-5D-5L VAS 9.3 (7.8, 10.9) 23.3* (21.4, 25.1) 9.0 (7.4, 10.5) 26.1* (24.4, 27.9) DAPSA-REM, n a 539 101 526 115 HAQ-DI −0.36 (−0.39, −0.32) −0.63* (−0.71, −0.55) −0.39 (−0.43, −0.35) −0.71* (−0.78, −0.63) SF-36 PCS 6.99 (6.39, 7.59) 14.54* (13.22, 15.86) 7.43 (6.82, 8.03) 15.16* (13.91, 16.40) EQ-5D-5L Index 0.14 (0.13, 0.15) 0.27* (0.24, 0.30) 0.15 (0.14, 0.16) 0.29* (0.26, 0.31) EQ-5D-5L VAS 12.7 (11.3, 14.0) 26.7* (23.7, 29.8) 13.3 (11.9, 14.7) 30.0* (27.1, 32.8) *p&lt;0.0001 vs non-responder (statistical significance was exploratory in nature) a n may vary by PRO assessed Conclusion: Among UPA-treated pts with PsA, improvements in quality of life and physical function were greater in pts who achieved MDA or DAPSA-REM than in those who did not. Despite DAPSA-REM being a more stringent measure (achieved by a smaller proportion of patients), these improvements were similar between MDA and DAPSA-REM responders. References: [1]McInnes I, et al. Ann Rheum Dis 2020;79(Suppl 1):16–7; 2. Mease PJ, et al. Ann Rheum Dis 2020 Figure 1. Acknowledgements: AbbVie funded this study; contributed to its design; participated in data collection, analysis, and interpretation of the data; and participated in the writing, review, and approval of the abstract. No honoraria or payments were made for authorship. Medical writing support was provided by Laura Chalmers, PhD, of 2 the Nth (Cheshire, UK), and was funded by AbbVie. Disclosure of Interests: Arthur Kavanaugh Grant/research support from: Research grants and/or personal fees from AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, and Pfizer, Philip J Mease Grant/research support from: Research grants and personal fees from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, and Janssen; and personal fees from Boehringer Ingelheim, Galapagos, Genentech, and Gilead, Kevin Douglas Employee of: Employee of AbbVie and may own stock or options, Frank Behrens Grant/research support from: Research grants from Celgene, Chugai, Janssen, Pfizer, and Roche; personal fees from AbbVie, Boehringer Ingelheim, Celgene, Chugai, Eli Lilly, Genzyme, Janssen, MSD, Novartis, Pfizer, Roche, and Sanofi; and investigator fees from Eli Lilly, Derek Haaland Speakers bureau: Advisory board/speaker bureau membership for AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, GSK, Janssen, Novartis, Pfizer, Roche, Sanofi, and Takeda, Consultant of: Honoraria or other fees from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GSK, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, Takeda, and UCB, Grant/research support from: Research grants from AbbVie, Adiga Life Sciences, Amgen, Bristol-Myers Squibb, Can-Fite Biopharma, Celgene, Eli Lilly, Gilead, GSK, Janssen, Novartis, Pfizer, Regeneron, Sanofi Genzyme, and UCB, Penelope Palominos Speakers bureau: Advisory board/speaker bureau membership for Janssen and Novartis, Consultant of: Personal fees from AbbVie, Grant/research support from: Research support from Novartis, Pfizer, and Roche, Apinya Lertratanakul Employee of: Employee of AbbVie and may own stock or options, Michael Lane Employee of: Employee of AbbVie and may own stock or options, Ralph Lippe Employee of: Employee of AbbVie and may own stock or options, Daniel Aletaha Consultant of: AbbVie, Grünenthal, Janssen, Medac, Mitsubishi Tanabe, MSD, Pfizer, Roche, and UCB, Grant/research support from: AbbVie, Grünenthal, Janssen, Medac, Mitsubishi Tanabe, MSD, Pfizer, Roche, and UCB, Peter Nash Grant/research support from: Received honoraria and research support from AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Gilead/Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Samsung, Sanofi, and UCB.