Upadacitinib for Axial Spondyloarthritis: a Meta-analysis of Efficacy and Safety

Overview

Journal Clin Rheumatol

Publisher Springer

Specialty Rheumatology

Date 2024 Jun 14

PMID 38874670

Authors

HanMing Tang

Xiaochen Liu

Jie Zhao

ZhiKun Tang

Zhiyong Zheng

WenZhe Bai

Affiliations

Soon will be listed here.

Abstract

To explore the effectiveness and safety of upadacitinib for managing axial spondyloarthritis. Four databases (PubMed, EMBASE, Cochrane, and Web of Science) were applied to search randomized controlled trials (RCTs) for assessing upadacitinib treatment for axial spondyloarthritis published until January 2024. Five RCTs involving 1,246 participants were included. The upadacitinib group had significantly higher percentages of participants achieving Assessment of spondyloarthritis international society (ASAS) 20, ASAS40, ASAS partial remission, Bath ankylosing spondylitis disease activity index (BASDAI) 50, Ankylosing Spondylitis Disease Activity Score (ASDAS) low disease activity, ASDAS inactive disease, ASDAS clinically important improvement, and ASDAS major improvement, except for Work Productivity and Activity Impairment (WPAI) absenteeism. Obvious improvements were observed in the upadacitinib group for ASDAS (CRP), BASDAI, Modified BASDAI, Bath Ankylosing Spondylitis Functional Index (BASFI), Canadian Spondyloarthritis Research Consortium (SPARCC) MRI spine, SPARCC MRI sacroiliac joint, Ankylosing Spondylitis Quality of Life (ASQoLS), ASAS Health Index, Bath Ankylosing Spondylitis Metrology Index (BASMI), Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), Total Back Pain, Nocturnal Back Pain, WPAI overall work impairment, WPAI presenteeism, and WPAI activity impairment. Adverse events (AEs) and serious adverse events (SAEs) incidence rates showed no significant difference differ between upadacitinib and placebo groups. Subgroup analysis revealed that disease subtype and age did not significantly affect efficacy, and upadacitinib demonstrated comparable efficacy to adalimumab for axial spondyloarthritis. Upadacitinib exhibited satisfactory efficacy in treating axial spondyloarthritis, reducing disease activity and significantly enhancing patients' physical function, emotional well-being, and social engagement. This meta-analysis offers robust evidence supporting upadacitinib as a new treatment for axial spondyloarthritis patients.

References

Sieper J, Poddubnyy D . Axial spondyloarthritis. Lancet. 2017; 390(10089):73-84. DOI: 10.1016/S0140-6736(16)31591-4. View

Vander Cruyssen B, Ribbens C, Boonen A, Mielants H, De Vlam K, Lenaerts J . The epidemiology of ankylosing spondylitis and the commencement of anti-TNF therapy in daily rheumatology practice. Ann Rheum Dis. 2007; 66(8):1072-7. PMC: 1954702. DOI: 10.1136/ard.2006.064543. View

Rudwaleit M, van der Heijde D, Landewe R, Listing J, Akkoc N, Brandt J . The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis. 2009; 68(6):777-83. DOI: 10.1136/ard.2009.108233. View

Maksymowych W . The role of imaging in the diagnosis and management of axial spondyloarthritis. Nat Rev Rheumatol. 2019; 15(11):657-672. DOI: 10.1038/s41584-019-0309-4. View

Danve A, Deodhar A . Treatment of axial spondyloarthritis: an update. Nat Rev Rheumatol. 2022; 18(4):205-216. DOI: 10.1038/s41584-022-00761-z. View

van der Heijde D, Ramiro S, Landewe R, Baraliakos X, Van den Bosch F, Sepriano A . 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis. Ann Rheum Dis. 2017; 76(6):978-991. DOI: 10.1136/annrheumdis-2016-210770. View

Banerjee S, Biehl A, Gadina M, Hasni S, Schwartz D . JAK-STAT Signaling as a Target for Inflammatory and Autoimmune Diseases: Current and Future Prospects. Drugs. 2017; 77(5):521-546. PMC: 7102286. DOI: 10.1007/s40265-017-0701-9. View

van der Heijde D, Baraliakos X, Gensler L, Maksymowych W, Tseluyko V, Nadashkevich O . Efficacy and safety of filgotinib, a selective Janus kinase 1 inhibitor, in patients with active ankylosing spondylitis (TORTUGA): results from a randomised, placebo-controlled, phase 2 trial. Lancet. 2018; 392(10162):2378-2387. DOI: 10.1016/S0140-6736(18)32463-2. View

van der Heijde D, Deodhar A, Wei J, Drescher E, Fleishaker D, Hendrikx T . Tofacitinib in patients with ankylosing spondylitis: a phase II, 16-week, randomised, placebo-controlled, dose-ranging study. Ann Rheum Dis. 2017; 76(8):1340-1347. PMC: 5738601. DOI: 10.1136/annrheumdis-2016-210322. View

10.

Deodhar A, Sliwinska-Stanczyk P, Xu H, Baraliakos X, Gensler L, Fleishaker D . Tofacitinib for the treatment of ankylosing spondylitis: a phase III, randomised, double-blind, placebo-controlled study. Ann Rheum Dis. 2021; 80(8):1004-1013. PMC: 8292568. DOI: 10.1136/annrheumdis-2020-219601. View

11.

Parmentier J, Voss J, Graff C, Schwartz A, Argiriadi M, Friedman M . In vitro and in vivo characterization of the JAK1 selectivity of upadacitinib (ABT-494). BMC Rheumatol. 2019; 2:23. PMC: 6390583. DOI: 10.1186/s41927-018-0031-x. View

12.

Mohamed M, Beck D, Camp H, Othman A . Preferential Inhibition of JAK1 Relative to JAK3 by Upadacitinib: Exposure-Response Analyses of Ex Vivo Data From 2 Phase 1 Clinical Trials and Comparison to Tofacitinib. J Clin Pharmacol. 2019; 60(2):188-197. PMC: 6973126. DOI: 10.1002/jcph.1513. View

13.

Cumpston M, Li T, Page M, Chandler J, Welch V, Higgins J . Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions. Cochrane Database Syst Rev. 2019; 10:ED000142. PMC: 10284251. DOI: 10.1002/14651858.ED000142. View

14.

Higgins J, Thompson S . Quantifying heterogeneity in a meta-analysis. Stat Med. 2002; 21(11):1539-58. DOI: 10.1002/sim.1186. View

15.

Baraliakos X, Ranza R, Ostor A, Ciccia F, Coates L, Rednic S . Efficacy and safety of upadacitinib in patients with active psoriatic arthritis and axial involvement: results from two phase 3 studies. Arthritis Res Ther. 2023; 25(1):56. PMC: 10084601. DOI: 10.1186/s13075-023-03027-5. View

16.

Deodhar A, Van den Bosch F, Poddubnyy D, Maksymowych W, van der Heijde D, Kim T . Upadacitinib for the treatment of active non-radiographic axial spondyloarthritis (SELECT-AXIS 2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2022; 400(10349):369-379. DOI: 10.1016/S0140-6736(22)01212-0. View

17.

van der Heijde D, Baraliakos X, Sieper J, Deodhar A, Inman R, Kameda H . Efficacy and safety of upadacitinib for active ankylosing spondylitis refractory to biological therapy: a double-blind, randomised, placebo-controlled phase 3 trial. Ann Rheum Dis. 2022; 81(11):1515-1523. PMC: 9606523. DOI: 10.1136/ard-2022-222608. View

18.

van der Heijde D, Song I, Pangan A, Deodhar A, Van den Bosch F, Maksymowych W . Efficacy and safety of upadacitinib in patients with active ankylosing spondylitis (SELECT-AXIS 1): a multicentre, randomised, double-blind, placebo-controlled, phase 2/3 trial. Lancet. 2019; 394(10214):2108-2117. DOI: 10.1016/S0140-6736(19)32534-6. View

19.

Mease P, Lertratanakul A, Anderson J, Papp K, Van den Bosch F, Tsuji S . Upadacitinib for psoriatic arthritis refractory to biologics: SELECT-PsA 2. Ann Rheum Dis. 2020; 80(3):312-320. PMC: 7892371. DOI: 10.1136/annrheumdis-2020-218870. View

20.

McInnes I, Anderson J, Magrey M, Merola J, Liu Y, Kishimoto M . Trial of Upadacitinib and Adalimumab for Psoriatic Arthritis. N Engl J Med. 2021; 384(13):1227-1239. DOI: 10.1056/NEJMoa2022516. View