POS0050 EFFICACY AND SAFETY OF UPADACITINIB IN PATIENTS WITH ACTIVE NON-RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS: 2-YEAR DATA FROM THE PHASE 3 SELECT-AXIS 2 STUDY

Background:

Upadacitinib (UPA), an oral reversible JAK inhibitor, has demonstrated efficacy compared with placebo (PBO) through 52 weeks (wks) in patients (pts) with nr-axSpA in the SELECT-AXIS 2 study, with an acceptable safety profile.[1-3]

Objectives:

To assess the 2-year (wk 104) safety and efficacy of UPA 15 mg once daily (QD) in pts with nr-axSpA in SELECT-AXIS 2, including its effect on inflammation in the sacroiliac joints and the spine on MRI, and radiographic progression in the spine.

Methods:

The design of the SELECT-AXIS 2 nr-axSpA study has been described previously.[1,2] Pts who completed the 52-wk double-blind PBO-controlled period could enter a long-term extension (LTE) for an additional 52 wks and receive open-label UPA 15 mg QD. Efficacy and safety were evaluated in pts receiving continuous UPA and those switching from PBO to UPA at wk 52. Efficacy endpoints included ASAS40, ASDAS low disease activity (LDA), and inactive disease (ID); and mean change from baseline (BL) in ASDAS, total and nocturnal back pain, AS Quality of Life (ASQoL), and ASAS Health Index (HI). Data are presented using 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) for binary endpoints. AO with mixed model repeated measures (AO-MMRM) analyses are used for continuous endpoints. Active inflammation on MRI was assessed by SpondyloArthritis Research Consortium of Canada (SPARCC) scores (SI joints and spine; AO-MMRM) and radiographic progression was assessed by modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS; AO-ANCOVA). Treatment-emergent adverse events are presented as exposure-adjusted event rates (events/100 patient-years [E/100 PY]).

Results:

Of 314 pts randomized at study entry, 271 entered the LTE (continuous UPA, n=133; PBO to UPA, n=138) and 239 (76.1%) completed 104 wks (continuous UPA, n=123; PBO to UPA, n=116). Response rates for ASAS40, ASDAS LDA and ID, and mean change from BL in ASDAS were maintained from wk 52 to wk 104 in the continuous UPA group; in the PBO to UPA group, response rates gradually improved through wk 104, and were generally similar to the continuous UPA group at wk 104 for most efficacy endpoints (Figure 1). Improvements from BL to wk 104 in the continuous UPA and PBO to UPA groups were comparable for total back pain (-4.47 vs -4.32, respectively) and nocturnal back pain (-4.33 vs -4.37), as well as ASQoL (-7.37 vs -6.69) and ASAS HI (-4.85 vs -4.25). Mean changes from BL to wk 104 in MRI SPARCC spine scores were -0.72 (BL mean: 2.11) and -0.47 (BL: 1.22) in the continuous UPA group and the PBO to UPA group, respectively; SI joints scores were -2.33 (BL: 5.13) and -2.30 (BL: 3.37). The least squares mean changes from BL to wk 104 in mSASSS scores were 0.00 and 0.02 for continuous UPA and PBO to UPA, respectively. Only one pt in the PBO to UPA group showed radiographic progression (change from BL in mSASSS ≥2). Safety is reported in 286 pts (378.3 PY) who received ≥1 dose of UPA. Rates of serious AEs and AEs leading to discontinuation of study drug were 8.7 and 5.3 E/100 PY, respectively, and no deaths occurred (Figure 2). Rates of MACE, VTE, and malignancy (excluding non-melanoma skin cancer) were 0.5, 0.8, and 0.3 E/100 PY, respectively, and in line with UPA 15 mg QD treatment in other rheumatologic indications.[3, 4]

Conclusion:

Through wk 104, sustained improvement in efficacy was observed in pts receiving continuous UPA. In pts who switched from PBO to UPA at wk 52, gradual improvements were observed across several disease measures, although response rates at wk 104 were marginally higher in pts receiving continuous UPA. UPA 15 mg QD was generally well tolerated through 104 wks and no new safety signals were identified.

REFERENCES:

[1] Deodhar A et al. Lancet 2022;400:369–79. [2] Van den Bosch F et al. EULAR 2023:PO80250. [3] Burmester GR et al. EULAR 2023:POS0657. [4] Burmester GR et al. RMD Open 2023;9:e002735.

Acknowledgements:

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 Amy Hall, MSc, of 2 the Nth (Cheshire, UK) and was funded by AbbVie.

Disclosure of Interests:

Filip van den Bosch AbbVie, Amgen, Galapagos, Janssen, Lilly, Merck, Novartis, Pfizer, and UCB Pharma., AbbVie, Amgen, Galapagos, Janssen, Lilly, Merck, Novartis, Pfizer, and UCB Pharma., Atul Deodhar AbbVie, BMS, Janssen, Lilly, Novartis, Pfizer, and UCB Pharma, AbbVie, BMS, Celgene, Lilly, MoonLake, Novartis, Pfizer, and UCB Pharma, Denis Poddubnyy AbbVie, Biocad, BMS, Galapagos, Gilead, GSK, Janssen, Lilly, MSD, Medscape, MoonLake, Novartis, Peervoice, Pfizer, Roche, Samsung Bioepis, and UCB Pharma, AbbVie, Biocad, BMS, Galapagos, Gilead, GSK, Janssen, Lilly, MSD, Medscape, MoonLake, Novartis, Peervoice, Pfizer, Roche, Samsung Bioepis, and UCB Pharma, AbbVie, Lilly, MSD, Novartis, and Pfizer, 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, Désirée van der Heijde AbbVie, ArgenX, Bayer, BMS, Galapagos, Gilead, GSK, Janssen, Lilly, Novartis, Pfizer, Takeda, and UCB Pharma, Tae-Hwan Kim AbbVie, Celltrion, Kirin, Lilly, and Novartis, Mitsumasa Kishimoto AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Chugai, Daiichi Sankyo, Eisai, Gilead, Janssen, Lilly, Novartis, Ono Pharma, Pfizer, Tanabe-Mitsubishi, and UCB Pharma, Xenofon Baraliakos AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, and UCB Pharma, AbbVie, BMS, Chugai, MSD, Novartis, Pfizer, and UCB Pharma, AbbVie and Novartis, Yihan Li AbbVie, AbbVie, Ivan Lagunes AbbVie, AbbVie, In-Ho Song AbbVie, AbbVie, Peter K Wung AbbVie, AbbVie, Anna Shmagel AbbVie, AbbVie.