Efficacy and safety of upadacitinib in patients with ankylosing spondylitis refractory to biologic therapy: 1-year results from the open-label extension of a phase III study

Arthritis Research & Therapy

Research

In-Ho Song¹  Peter Wung¹  Yihan Li¹  Xianwei Bu¹  Anna Shmagel¹  Atul Deodhar²  Joachim Sieper³  Hideto Kameda⁴  Désirée van der Heijde⁵  Xenofon Baraliakos⁶  Robert D. Inman⁷ 

[1] AbbVie Inc, North Chicago, IL, USA;Division of Arthritis & Rheumatic Diseases, Oregon Health & Science University, Portland, OR, USA;Gastroenterology, Infectious Diseases and Rheumatology, Charité Universitätsmedizin Berlin, Berlin, Germany;Internal Medicine, Toho University, Tokyo, Japan;Rheumatology, Leiden University Medical Center, Leiden, The Netherlands;Rheumazentrum Ruhrgebiet Herne, Ruhr-University Bochum, Herne, Germany;Schroeder Arthritis Institute, University Health Network, and University of Toronto, Toronto, ON, Canada;

关键词: Ankylosing spondylitis;    Janus kinase inhibitor;    Open-label extension;    Upadacitinib;    Biologic;    Tumor necrosis factor;    Inadequate response;    Refractory;   

DOI  :  10.1186/s13075-023-03128-1

 received in 2023-04-17, accepted in 2023-07-29,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundUpadacitinib, a Janus kinase inhibitor, has demonstrated efficacy and an acceptable safety profile in patients with ankylosing spondylitis (AS) in the phase III SELECT-AXIS programs. We report the 1-year efficacy and safety in patients with AS and an inadequate response to biologic disease-modifying antirheumatic drugs (bDMARD-IR) from the SELECT-AXIS 2 study.MethodsPatients ≥ 18 years with active AS who met the modified New York criteria for AS and were bDMARD-IR received double-blind upadacitinib 15 mg once daily (QD) or placebo for 14 weeks. Patients who completed 14 weeks could enter an open-label extension and receive upadacitinib 15 mg QD for up to 2 years. Efficacy endpoints included the percentage of patients achieving ≥ 40% improvement in Assessment of SpondyloArthritis international Society response (ASAS40), Ankylosing Spondylitis Disease Activity Score (ASDAS) low disease activity (LDA), and ASDAS inactive disease (ID); and change from baseline in total and nocturnal back pain, and Bath Ankylosing Spondylitis Functional Index (BASFI). Subgroup analyses (bDMARD lack of efficacy versus intolerance, and prior tumor necrosis factor inhibitor [TNFi] versus interleukin-17 inhibitor [IL-17i] exposure) were conducted. Binary and continuous efficacy endpoints were assessed using non-responder imputation with multiple imputation (NRI-MI) and as observed (AO) analyses; and mixed-effects model repeated measures (MMRM) and AO, respectively. Safety was assessed based on adverse events. Data through week 52 are reported.ResultsOf 420 randomized patients, 366 (continuous upadacitinib: n = 181; placebo to upadacitinib: n = 185) completed 52 weeks of treatment. At week 52, in the continuous upadacitinib and placebo to upadacitinib groups, ASAS40, ASDAS LDA, and ASDAS ID were achieved by 66% and 65%, 57% and 55%, and 26% and 25% (all NRI-MI); and change from baseline in total back pain, nocturnal back pain, and BASFI was -4.5 and -4.3, -4.6 and -4.4, and -3.6 and -3.5 (all MMRM), respectively. No new safety risks were identified. Subgroup analyses were consistent with the overall study population.ConclusionsUpadacitinib 15 mg QD demonstrated sustained improvement up to 52 weeks in bDMARD-IR patients with AS. Efficacy was generally similar in patients with lack of efficacy versus intolerance to bDMARDs and prior TNFi versus IL-17i exposure.Trial registrationNCT02049138.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

【 图 表 】

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Fig. 1