POS0798 EFFICACY, SAFETY AND RADIOGRAPHIC OUTCOMES FROM THE PHASE 3 SELECT-AXIS 2 STUDY OF UPADACITINIB IN PATIENTS WITH ACTIVE ANKYLOSING SPONDYLITIS AND AN INADEQUATE RESPONSE TO BIOLOGIC DMARD THERAPY: 2-YEAR DATA
Authors: X. Baraliakos, D. Van der Heijde, J. Sieper, R. Inman, H. Kameda, W. P. Maksymowych, A. Shmagel, I. Lagunes, X. Bu, P. K. Wung, A. Deodhar
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Upadacitinib (UPA), an oral reversible JAK inhibitor, has shown efficacy and an acceptable safety profile in patients (pts) with AS (r-axSpA) in the SELECT-AXIS 1 and 2 studies, including pts with an inadequate response or intolerance to biologic DMARDs (bDMARD-IR) through 1 year in SELECT-AXIS 2. [1,2] <h3>Objectives:</h3> To assess the 2-year efficacy, safety, and radiographic outcomes following treatment with UPA 15 mg once daily (QD) in bDMARD-IR pts with active AS in SELECT-AXIS 2. <h3>Methods:</h3> The SELECT-AXIS 2 AS bDMARD-IR study design has been described previously. [1,2] Following a 14-week (wk) placebo (PBO)-controlled period, pts were eligible to enter a long-term extension and receive open-label UPA 15 mg QD. Efficacy was evaluated over 104wks in pts who received continuous UPA, and those who switched from PBO to UPA at wk14. Efficacy endpoints included ASAS40, ASAS partial remission (ASAS PR), ASDAS low disease activity (LDA; &lt;2.1), and ASDAS inactive disease (ID; &lt;1.3); and mean change from baseline (BL) in ASDAS, total back pain, BASFI, and ASAS health index (HI) scores. As observed (AO) and AO with non-responder imputation analyses (AO-NRI), where all observed data are used in the analysis and missing data are imputed as non-responders, are presented for binary endpoints. AO with mixed model repeated measures (AO-MMRM) analyses are used for continuous endpoints. Imaging outcomes included SpondyloArthritis Research Consortium of Canada (SPARCC) MRI inflammation scores (AO-MMRM) and modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS; AO-ANCOVA). Safety was assessed through wk104 in all pts who received ≥1 UPA dose. Treatment-emergent adverse events (TEAEs) are presented as exposure-adjusted event rates (events/100 patient-years [E/100 PY]). <h3>Results:</h3> Of 420 randomized pts who received the study drug (continuous UPA: n=211; PBO to UPA: n=209), 331 (78.8%) completed 104wks of treatment (n=163 and n=168, respectively). Response rates for disease activity were maintained or improved from wk14 to wk104 in the continuous UPA group and at wk104 similar responses were achieved in the PBO to UPA group. Response rates at wk104 were comparable for the continuous UPA vs PBO to UPA groups, including ASAS40 (AO-NRI; 64.9% and 61.7%, respectively), ASAS PR (34.1% and 37.8%), ASDAS LDA (55.9% and 55.0%), and ASDAS ID (29.9% and 34.4%) (Figure 1). Mean change from BL was similar for continuous UPA vs PBO to UPA for ASDAS (-2.08 vs -2.04, respectively), total back pain (-4.86 vs -4.60), BASFI (-3.77 vs -3.73), and ASAS HI (-4.95 vs -4.55). Improvements from BL in MRI inflammation were maintained in both treatment groups. Mean change from BL in MRI SPARCC spine scores were -3.80 (BL mean: 9.97) and -4.55 (BL: 7.71) in the continuous UPA and PBO to UPA group, respectively; SI joints scores were -3.11 (BL: 5.98) and -3.96 (BL: 5.91). Most pts showed no radiographic progression (mean change from BL in mSASSS &lt;2 continuous UPA: 94.9%; PBO to UPA: 93.8%). The least squares mean change from BL to wk104 in mSASSS scores was 0.12 for continuous UPA and 0.20 PBO to UPA. Safety was reported in 414 pts (687.2 PY) who received ≥1 UPA dose. TEAEs, serious TEAEs, and discontinuation of study drug rates were 165.2, 8.7, and 3.6 E/100 PY, respectively; one death (polytrauma, previously reported) occurred before wk52 (0.1 E/100 PY). [1] Rates of major adverse cardiovascular events, venous thromboembolic events, and malignancy (excluding non-melanoma skin cancer) occurred at 0.3 E/100 PY (Figure 2). <h3>Conclusion:</h3> Efficacy was maintained or improved with UPA 15 mg to wk104 in bDMARD-IR pts with active AS and was similar in pts receiving continuous UPA compared with PBO to UPA. Inflammatory activity on MRI and rates of radiographic progression at wk104 were low in both groups. UPA 15 mg was generally well tolerated, with no new safety signals identified. <h3>REFERENCES:</h3> [1] Baraliakos X et al. Arthritis Res Ther. 2023;25:172. [2] van der Heijde D et al. Ann Rheum Dis. 2022;81:1515–23. <h3>Acknowledgements:</h3> AbbVie and the authors thank the participants, study sites, and study investigators who are participating in this study. AbbVie funded this study and contributed to its design, research, analysis, data collection, interpretation of data, and the review and approval of this abstract. All authors had access to relevant data and participated in the drafting, review, and approval of this abstract. No honoraria or payments were made for authorship. Medical writing support was provided by Carl Davies, MSc, of 2 the Nth (Cheshire, UK) and was funded by AbbVie. <h3>Disclosure of Interests:</h3> Xenofon Baraliakos AbbVie, BMS, Chugai, MSD Novartis, Pfizer, and UCB Pharma, AbbVie, BMS, Chugai, MSD, Novartis, Pfizer, and UCB Pharma, AbbVie and Novartis, Désirée van der Heijde AbbVie, ArgenX, Bayer, BMS, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, Takeda, and UCB Pharma, Joachim Sieper AbbVie, Merck, and Novartis, AbbVie, Merck, Novartis, and UCB, AbbVie, Merck, and UCB, Robert Inman AbbVie, Amgen, Janssen, Lilly, Novartis, Pfizer, and Sandoz., AbbVie, Amgen, Janssen, and Novartis, Hideto Kameda AbbVie, Asahi-Kasei, Eisai, Janssen, Lilly, Mitsubishi-Tanabe, and UCB, AbbVie, Janssen, Lilly, Novartis, Sanofi, and UCB, AbbVie, Asahi-Kasei, Boehringer Ingelheim, Eisai, Mitsubishi-Tanabe, and Taisho, Walter P Maksymowych AbbVie, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, Medscape, Novartis, Peervoice, Pfizer, and UCB Pharma, AbbVie, BMS, Celgene, Galapagos, Gilead, Janssen, Lilly, Medscape, Novartis, Peervoice, Pfizer, and UCB Pharma, AbbVie, Novartis, Pfizer, and UCB Pharma, Anna Shmagel AbbVie, Ivan Lagunes AbbVie, Xianwei Bu AbbVie, Peter K Wung AbbVie, Atul Deodhar AbbVie, BMS, Janssen, Lilly, Novartis, Pfizer, and UCB Pharma, AbbVie, BMS, Celgene, Lilly, MoonLake, Novartis, Pfizer, and UCB Pharma.