Skip to content
2000
Volume 21, Issue 4
  • ISSN: 1573-3971
  • E-ISSN: 1875-6360

Abstract

Introduction

Upadacitinib, a selective JAK1 inhibitor, has demonstrated promising results in the treatment of axial Spondyloarthritis (AxSpA). AxSpA management remains challenging since there is a gap in knowledge regarding the potential effect of upadacitinib in axSpA patients. Exploring novel therapeutic options is crucial. Therefore, we performed this systematic review and meta-analysis to summarize and synthesize results collected from available randomized- controlled trials (RCTs) about the efficacy and safety of upadacitinib for patients with axSpA.

Methods

A systematic literature search of Medline PubMed, Web of Science, Scopus, EBSCO, and Cochrane Central was conducted in October 2023. Relevant RCTs were selected, and their data were extracted and analyzed using the RevMan 5.4 software. The main outcomes were assessment in Spondylarthritis International Society (ASAS) 20, ASAS40, SPARCC MRI sacroiliac joint, and Bath Ankylosing Spondylitis disease activity index (BASDAI) 50.

Results

Three RCTs with a total of 920 participants were included in this study. Upadacitinib showed significant improvement in the ASAS40 response, ASAS20 response, BASDAI50 response, and SPARCC MRI Sacroiliac Joint change from baseline compared to placebo at 14-week duration (RR 2.19, 95% CI (1.79 to 2.68), 0.00001), (RR 1.62, 95% CI (1.42 to 1.84), 0.00001), (RR 2.16, 95% CI (1.75 to 2.67), 0.00001), and (MD -3.32 points, 95% CI (-3.96 to -2.68), 0.00001) respectively. However, this efficacy decreased after the 52-week duration in terms of ASAS40 RR 2.19 . 1.02, ASAS20 RR 1.62 . 0.98, BASDAI 50 RR 2.16 . 1.05, and ASAS Partial Remission RR 3.82 . 1.07.

 Conclusion

Upadacitinib 15 mg showed satisfactory and promising efficacy in the treatment of AxSpA, with no difference in safety profile compared to the placebo.

Loading

Article metrics loading...

/content/journals/crr/10.2174/0115733971296457240805064237
2024-08-19
2025-10-27
Loading full text...

Full text loading...

References

  1. SieperJ. PoddubnyyD. Axial spondyloarthritis.Lancet201739010089738410.1016/S0140‑6736(16)31591‑428110981
    [Google Scholar]
  2. López-MedinaC. RamiroS. van der HeijdeD. SieperJ. DougadosM. MoltoA. Characteristics and burden of disease in patients with radiographic and non-radiographic axial Spondyloarthritis: a comparison by systematic literature review and meta-analysis.RMD Open201952e00110810.1136/rmdopen‑2019‑00110831803500
    [Google Scholar]
  3. ZhaoS.S. ErmannJ. XuC. LyuH. TedeschiS.K. LiaoK.P. YoshidaK. MootsR.J. GoodsonN.J. SolomonD.H. Comparison of comorbidities and treatment between ankylosing spondylitis and non-radiographic axial spondyloarthritis in the United States.Rheumatology (Oxford)201958112025203010.1093/rheumatology/kez17131081033
    [Google Scholar]
  4. LandewéR. BraunJ. DeodharA. DougadosM. MaksymowychW.P. MeaseP.J. ReveilleJ.D. RudwaleitM. van der HeijdeD. StachC. HoepkenB. FichtnerA. CoteurG. de LonguevilleM. SieperJ. Efficacy of certolizumab pegol on signs and symptoms of axial spondyloarthritis including ankylosing spondylitis: 24-week results of a double-blind randomised placebo-controlled Phase 3 study.Ann. Rheum. Dis.2014731394710.1136/annrheumdis‑2013‑20423124013647
    [Google Scholar]
  5. DeodharA. MachadoPM. MørupM. TaiebV. WillemsD. OrmeM. Comparative efficacy and safety of bimekizumab in axial spondyloarthritis: A systematic literature review and network meta-analysis.Rheumatology (Oxford).202363511951205
    [Google Scholar]
  6. TangH. SinghB.S.M. FongW. Prevalence and factors associated with fatigue in patients with axial spondyloarthritis: A systematic review and meta-analysis.Rheumatol. Adv. Pract.202373rkad08410.1093/rap/rkad08437881507
    [Google Scholar]
  7. KiltzU. BaraliakosX. KarakostasP. IgelmannM. KalthoffL. KlinkC. KrauseD. Schmitz-BortzE. FlöreckeM. BollowM. BraunJ. Do patients with non-radiographic axial spondylarthritis differ from patients with ankylosing spondylitis?Arthritis Care Res. (Hoboken)20126491415142210.1002/acr.2168822505331
    [Google Scholar]
  8. PoddubnyyD. SieperJ. AkarS. Muñoz-FernándezS. HaibelH. HojnikM. GanzF. InmanR.D. Characteristics of patients with axial spondyloarthritis by geographic regions: PROOF multicountry observational study baseline results.Rheumatology (Oxford)20226183299330810.1093/rheumatology/keab90134897381
    [Google Scholar]
  9. van der HeijdeD. RamiroS. LandewéR. BaraliakosX. Van den BoschF. SeprianoA. RegelA. CiureaA. DagfinrudH. DougadosM. van GaalenF. GéherP. van der Horst-BruinsmaI. InmanR.D. JongkeesM. KiltzU. KvienT.K. MachadoP.M. Marzo-OrtegaH. MoltoA. Navarro-CompànV. OzgocmenS. Pimentel-SantosF.M. ReveilleJ. RudwaleitM. SieperJ. Sampaio-BarrosP. WiekD. BraunJ. 2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis.Ann. Rheum. Dis.201776697899110.1136/annrheumdis‑2016‑21077028087505
    [Google Scholar]
  10. WardM.M. DeodharA. GenslerL.S. DubreuilM. YuD. KhanM.A. HaroonN. BorensteinD. WangR. BiehlA. FangM.A. LouieG. MajithiaV. NgB. BighamR. PianinM. ShahA.A. SullivanN. TurgunbaevM. OristaglioJ. TurnerA. MaksymowychW.P. CaplanL. 2019 update of the american college of rheumatology/spondylitis association of america/spondyloarthritis research and treatment network recommendations for the treatment of ankylosing spondylitis and nonradiographic axial spondyloarthritis.Arthritis Rheumatol.201971101599161310.1002/art.4104231436036
    [Google Scholar]
  11. FragoulisG.E. LiavaC. DaoussisD. AkriviadisE. GaryfallosA. DimitroulasT. Inflammatory bowel diseases and spondyloarthropathies: From pathogenesis to treatment.World J. Gastroenterol.201925182162217610.3748/wjg.v25.i18.216231143068
    [Google Scholar]
  12. SeprianoA. RamiroS. van der HeijdeD. LandewéR. Biological DMARDs and disease modification in axial spondyloarthritis: A review through the lens of causal inference.RMD Open202172e00165410.1136/rmdopen‑2021‑00165434253683
    [Google Scholar]
  13. MeaseP.J. LiuM. RebelloS. KangH. YiE. ParkY. GreenbergJ.D. Comparative disease burden in patients with rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis: Data from two corrona registries.Rheumatol. Ther.20196452954210.1007/s40744‑019‑00172‑931529278
    [Google Scholar]
  14. Navarro-CompánV. Plasencia-RodríguezC. de MiguelE. Diaz del CampoP. BalsaA. GratacósJ. Switching biological disease- modifying antirheumatic drugs in patients with axial spondyloarthritis: results from a systematic literature review.RMD Open201732e00052410.1136/rmdopen‑2017‑00052429071119
    [Google Scholar]
  15. TanakaY. MaeshimaY. YamaokaK. In vitro and in vivo analysis of a JAK inhibitor in rheumatoid arthritis.Ann. Rheum. Dis.201271Suppl. 2i70i7410.1136/annrheumdis‑2011‑20059522460142
    [Google Scholar]
  16. O’SheaJ.J. HollandS.M. StaudtL.M. JAKs and STATs in immunity, immunodeficiency, and cancer.N. Engl. J. Med.2013368216117010.1056/NEJMra120211723301733
    [Google Scholar]
  17. MeaseP. HallS. FitzGeraldO. van der HeijdeD. MerolaJ.F. Avila-ZapataF. CieślakD. GrahamD. WangC. MenonS. HendrikxT. KanikK.S. Tofacitinib or adalimumab versus placebo for psoriatic arthritis.N. Engl. J. Med.2017377161537155010.1056/NEJMoa161597529045212
    [Google Scholar]
  18. van der HeijdeD. BaraliakosX. GenslerL.S. MaksymowychW.P. TseluykoV. NadashkevichO. Abi-SaabW. TassetC. MeulenersL. BesuyenR. HendrikxT. MozaffarianN. LiuK. GreerJ.M. DeodharA. LandewéR. 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.Lancet2018392101622378238710.1016/S0140‑6736(18)32463‑230360970
    [Google Scholar]
  19. TanakaY. The JAK inhibitors: Do they bring a paradigm shift for the management of rheumatic diseases?Rheumatology (Oxford)201958Suppl. 1i1i310.1093/rheumatology/key28030806705
    [Google Scholar]
  20. ChoyE.H. Clinical significance of Janus Kinase inhibitor selectivity.Rheumatology (Oxford)201958695396210.1093/rheumatology/key33930508136
    [Google Scholar]
  21. DeodharA. Van den BoschF. PoddubnyyD. MaksymowychW.P. van der HeijdeD. KimT.H. KishimotoM. BlancoR. DuanY. LiY. PanganA.L. WungP. SongI.H. Upadacitinib for the treatment of active non-radiographic axial spondyloarthritis (SELECT-AXIS 2): A randomised, double-blind, placebo-controlled, phase 3 trial.Lancet20224001034936937910.1016/S0140‑6736(22)01212‑035908570
    [Google Scholar]
  22. van der HeijdeD. SongI.H. PanganA.L. DeodharA. van den BoschF. MaksymowychW.P. KimT.H. KishimotoM. EverdingA. SuiY. WangX. ChuA.D. SieperJ. 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.Lancet2019394102142108211710.1016/S0140‑6736(19)32534‑631732180
    [Google Scholar]
  23. FukuiS. KawaaiS. SawadaH. KishimotoM. Upadacitinib for the treatment of adults with active non-radiographic axial spondyloarthritis (nr-axSpa).Expert Rev. Clin. Immunol.202320214115337955181
    [Google Scholar]
  24. van der HeijdeD. DeodharA. MaksymowychW.P. SieperJ. Van den BoschF. KimT.H. KishimotoM. ÖstörA.J. CombeB. SuiY. DuanY. WungP.K. SongI.H. Upadacitinib in active ankylosing spondylitis: results of the 2-year, double-blind, placebo-controlled SELECT-AXIS 1 study and open-label extension.RMD Open202282e00228010.1136/rmdopen‑2022‑00228035896281
    [Google Scholar]
  25. DeodharA. van der HeijdeD. SieperJ. Van den BoschF. MaksymowychW.P. KimT.H. KishimotoM. OstorA. CombeB. SuiY. ChuA.D. SongI.H. Safety and efficacy of upadacitinib in patients with active ankylosing spondylitis and an inadequate response to nonsteroidal antiinflammatory drug therapy: one-year results of a double-blind, placebo-controlled study and open-label extension.Arthritis Rheumatol.2022741708010.1002/art.4191134196498
    [Google Scholar]
  26. TanakaY. LuoY. O’SheaJ.J. NakayamadaS. Janus kinase-targeting therapies in rheumatology: A mechanisms-based approach.Nat. Rev. Rheumatol.202218313314510.1038/s41584‑021‑00726‑834987201
    [Google Scholar]
  27. KumthekarA. BittarM. DubreuilM. Educational needs and challenges in axial spondyloarthritis.Curr. Opin. Rheumatol.202133431331810.1097/BOR.000000000000080633973547
    [Google Scholar]
  28. HoffmannB. Mulrow CD. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews.BMJ.2021372n71
    [Google Scholar]
  29. Cochrane Handbook for Systematic Reviews of Interventions.Available from: https://training.cochrane.org/handbook(accessed on 15-7-2024)
  30. OuzzaniM. HammadyH. FedorowiczZ. ElmagarmidA. Rayyan—a web and mobile app for systematic reviews.Syst. Rev.20165121010.1186/s13643‑016‑0384‑427919275
    [Google Scholar]
  31. SterneJ.A.C. SavovićJ. PageM.J. ElbersR.G. BlencoweN.S. BoutronI. CatesC.J. ChengH.Y. CorbettM.S. EldridgeS.M. EmbersonJ.R. HernánM.A. HopewellS. HróbjartssonA. JunqueiraD.R. JüniP. KirkhamJ.J. LassersonT. LiT. McAleenanA. ReevesB.C. ShepperdS. ShrierI. StewartL.A. TillingK. WhiteI.R. WhitingP.F. HigginsJ.P.T. RoB 2: A revised tool for assessing risk of bias in randomised trials.BMJ2019366l489810.1136/bmj.l489831462531
    [Google Scholar]
  32. SieperJ. RudwaleitM. BaraliakosX. BrandtJ. BraunJ. Burgos-VargasR. DougadosM. HermannK-G. LandewéR. MaksymowychW. van der HeijdeD. The Assessment of SpondyloArthritis international Society (ASAS) handbook: A guide to assess spondyloarthritis.Ann. Rheum. Dis.200968Suppl. 2ii1ii4410.1136/ard.2008.10401819433414
    [Google Scholar]
  33. LandewéR. van TubergenA. Clinical tools to assess and monitor spondyloarthritis.Curr. Rheumatol. Rep.20151774710.1007/s11926‑015‑0522‑326063534
    [Google Scholar]
  34. MaksymowychW.P. InmanR.D. SalonenD. DhillonS.S. WilliamsM. StoneM. Conner-spadyB. PalsatJ. LambertR.G.W. Spondyloarthritis research Consortium of Canada magnetic resonance imaging index for assessment of sacroiliac joint inflammation in ankylosing spondylitis.Arthritis Care Res.200553570370910.1002/art.2144516208659
    [Google Scholar]
  35. RudwaleitM. ListingJ. BrandtJ. BraunJ. SieperJ. Prediction of a major clinical response (BASDAI 50) to tumour necrosis factor blockers in ankylosing spondylitis.Ann. Rheum. Dis.200463666567010.1136/ard.2003.01638615037444
    [Google Scholar]
  36. MachadoP.M. LandewéR. van der HeijdeD. Ankylosing Spondylitis Disease Activity Score (ASDAS): 2018 update of the nomenclature for disease activity states.Ann. Rheum. Dis.201877101539154010.1136/annrheumdis‑2018‑21318429453216
    [Google Scholar]
  37. WeismanM.H. van der HeijdeD. ReveilleJ.D. Ankylosing Spondylitis and the Spondyloarthropathies.Elsevier2006
    [Google Scholar]
  38. DowardL.C. SpoorenbergA. CookS.A. WhalleyD. HelliwellP.S. KayL.J. McKennaS.P. TennantA. van der HeijdeD. ChamberlainM.A. Development of the ASQoL: a quality of life instrument specific to ankylosing spondylitis.Ann. Rheum. Dis.2003621202610.1136/ard.62.1.2012480664
    [Google Scholar]
  39. KiltzU. WendlingD. BraunJ. ASAS health index: The “all in one” for spondyloarthritis evaluation?J. Rheumatol.202047101457146010.3899/jrheum.20070833004479
    [Google Scholar]
  40. van der HeijdeD. LandewéR. FeldtkellerE. Proposal of a linear definition of the Bath Ankylosing Spondylitis Metrology Index (BASMI) and comparison with the 2-step and 10-step definitions.Ann. Rheum. Dis.200867448949310.1136/ard.2007.07472417728332
    [Google Scholar]
  41. Heuft-DorenboschL. SpoorenbergA. van TubergenA. LandewéR. van ver TempelH. MielantsH. DougadosM. van der HeijdeD. Assessment of enthesitis in ankylosing spondylitis.Ann. Rheum. Dis.200362212713210.1136/ard.62.2.12712525381
    [Google Scholar]
  42. EggerM. SmithG.D. SchneiderM. MinderC. Bias in meta-analysis detected by a simple, graphical test.BMJ1997315710962963410.1136/bmj.315.7109.6299310563
    [Google Scholar]
  43. van der HeijdeD. BaraliakosX. SieperJ. DeodharA. InmanR.D. KamedaH. ZengX. SuiY. BuX. PanganA.L. WungP. SongI.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.202281111515152310.1136/ard‑2022‑22260835788492
    [Google Scholar]
  44. BaraliakosX. van der HeijdeD. SieperJ. InmanR.D. KamedaH. LiY. BuX. ShmagelA. WungP. SongI.H. DeodharA. 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 Res. Ther.202325117210.1186/s13075‑023‑03128‑137723577
    [Google Scholar]
  45. RussellM.D. DeyM. FlintJ. DavieP. AllenA. CrossleyA. FrishmanM. GayedM. HodsonK. KhamashtaM. MooreL. PanchalS. PiperM. ReidC. SaxbyK. SchreiberK. SenvarN. TosounidouS. van de VenneM. WarburtonL. WilliamsD. YeeC.S. GordonC. GilesI. GilesI. RoddyE. ArmonK. AstellL. CottonC. DavidsonA. FordhamS. JonesC. JoyceC. KuttikatA. McLarenZ. MerrisonK. MewarD. MootooA. WilliamsE. British Society for Rheumatology guideline on prescribing drugs in pregnancy and breastfeeding: immunomodulatory anti-rheumatic drugs and corticosteroids.Rheumatology (Oxford)2023624e48e8810.1093/rheumatology/keac55136318966
    [Google Scholar]
/content/journals/crr/10.2174/0115733971296457240805064237
Loading
/content/journals/crr/10.2174/0115733971296457240805064237
Loading

Data & Media loading...

Supplements

PRISMA checklist is available as supplementary material on the publisher’s website along with the published article. Supplementary material, along with the published article, is available on the publisher’s website.

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test