Innovative approaches in axial spondyloarthritis: exploring emerging trends in treatment and management

Jagoda Rogowska; Wiktoria Balińska; Jakub Wąsik; Aleksandra Marek

doi:10.20883/medical.e1270

Authors

Jagoda Rogowska Medical University of Lodz https://orcid.org/0009-0004-5995-5802
Wiktoria Balińska Medical University of Lodz https://orcid.org/0009-0002-2615-7236
Jakub Wąsik Medical University of Lodz https://orcid.org/0009-0002-7145-8118
Aleksandra Marek Medical University of Lodz https://orcid.org/0009-0002-3391-5082

DOI:

https://doi.org/10.20883/medical.e1270

Keywords:

axial spondyloarthritis, biologics, JAK inhibitors, IL-17 inhibitors, treatment innovations, chronic inflammatory disease, disease management

Abstract

Background. Axial Spondyloarthritis (axSpA) is a chronic inflammatory disease affecting the axial skeleton, resulting in chronic pain, reduced mobility, and potential spinal fusion. Traditional therapies emphasise symptomatic control via nonsteroidal anti-inflammatory drugs (NSAIDs) and physical therapy. Recent advances, however, including biologic agents and JAK inhibitors, have opened new therapeutic possibilities.

Material and methods. A comprehensive literature review was conducted using databases such as PubMed and Scopus. The literature search included English-language publications between January 2018 and February 2024. We included clinical trials, meta-analyses, systematic reviews, cohort studies, and significant basic science studies. Publications outside these criteria or those in other languages were excluded. Methodological rigour and limitations of included studies were critically discussed.

Results. Key recent advances include biologic therapies targeting IL-17 and IL-23 cytokine pathways, demonstrating significant efficacy in controlling inflammation and improving function. Additionally, precision medicine, microbiome-based interventions, and advanced imaging techniques enhance personalised treatment strategies.

Conclusions. Integrating novel pharmacological approaches with lifestyle modifications presents a promising strategy for optimising axSpA management. Long-term studies are required to assess the full impact of these innovations on disease progression.

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References

Wenker KJ, Quint JM. Ankylosing Spondylitis. StatPearls, Treasure Island (FL): StatPearls Publishing; 2025.

Uslu S, Gulle S, Sen G, Cefle A, Yilmaz S, Kocaer SB, Yuce Inel T, Koca SS, Yolbas S, Ozturk MA, Senel S, Inanc N, Dalkilic HE, Soysal Gunduz O, Tufan A, Akar S, Birlik AM, Sari I, Akkoc N, Onen F. Assessing safety and efficacy of TNFi treatment in late onset ankylosing spondylitis: a TURKBIO registry study. Sci Rep 2024;14:14194. https://doi.org/10.1038/s41598-024-65180-4.

Parameswaran P, Lucke M. HLA-B27 Syndromes. StatPearls, Treasure Island (FL): StatPearls Publishing; 2025.

Ramiro S, Nikiphorou E, Sepriano A, Ortolan A, Webers C, Baraliakos X, Landewé RBM, Van Den Bosch FE, Boteva B, Bremander A, Carron P, Ciurea A, Van Gaalen FA, Géher P, Gensler L, Hermann J, De Hooge M, Husakova M, Kiltz U, López-Medina C, Machado PM, Marzo-Ortega H, Molto A, Navarro-Compán V, Nissen MJ, Pimentel-Santos FM, Poddubnyy D, Proft F, Rudwaleit M, Telkman M, Zhao SS, Ziade N, Van Der Heijde D. ASAS-EULAR recommendations for the management of axial spondyloarthritis: 2022 update. Annals of the Rheumatic Diseases 2023;82:19–34. https://doi.org/10.1136/ard-2022-223296.

Poddubnyy D, Heijde DVD. Therapeutic Controversies in Spondyloarthritis. Rheumatic Disease Clinics of North America 2012;38:601–11. https://doi.org/10.1016/j.rdc.2012.08.005.

Evangelatos G, Bamias G, Kitas GD, Kollias G, Sfikakis PP. The second decade of anti-TNF-a therapy in clinical practice: new lessons and future directions in the COVID-19 era. Rheumatol Int 2022;42:1493–511. https://doi.org/10.1007/s00296-022-05136-x.

Benlidayı IC. What are the potential benefits and harms of exercise programs for patients with ankylosing spondylitis? A Cochrane review summary with commentary. Turk J Phys Med Rehab 2020;66:84–7. https://doi.org/10.5606/tftrd.2020.6041.

Zhu W, He X, Cheng K, Zhang L, Chen D, Wang X, Qiu G, Cao X, Weng X. Ankylosing spondylitis: etiology, pathogenesis, and treatments. Bone Res 2019;7:22. https://doi.org/10.1038/s41413-019-0057-8.

Kenyon M, Maguire S, Rueda Pujol A, O’Shea F, McManus R. The genetic backbone of ankylosing spondylitis: how knowledge of genetic susceptibility informs our understanding and management of disease. Rheumatol Int 2022;42:2085–95. https://doi.org/10.1007/s00296-022-05174-5.

Pedersen SJ, Maksymowych WP. The Pathogenesis of Ankylosing Spondylitis: an Update. Curr Rheumatol Rep 2019;21:58. https://doi.org/10.1007/s11926-019-0856-3.

Li Z, Akar S, Yarkan H, Lee SK, Çetin P, Can G, Kenar G, Çapa F, Pamuk ON, Pehlivan Y, Cremin K, De Guzman E, Harris J, Wheeler L, Jamshidi A, Vojdanian M, Farhadi E, Ahmadzadeh N, Yüce Z, Dalkılıç E, Solmaz D, Akın B, Dönmez S, Sarı İ, Leo PJ, Kenna TJ, Önen F, Mahmoudi M, Brown MA, Akkoc N. Genome-wide association study in Turkish and Iranian populations identify rare familial Mediterranean fever gene (MEFV) polymorphisms associated with ankylosing spondylitis. PLoS Genet 2019;15:e1008038. https://doi.org/10.1371/journal.pgen.1008038.

Fei Y, Yu H, Wu Y, Gong S. The causal relationship between immune cells and ankylosing spondylitis: a bidirectional Mendelian randomization study. Arthritis Res Ther 2024;26:24. https://doi.org/10.1186/s13075-024-03266-0.

Agrawal P, Tote S, Sapkale B. Diagnosis and Treatment of Ankylosing Spondylitis. Cureus 2024. https://doi.org/10.7759/cureus.52559.

Alotaibi A, Albarrak D, Alammari Y. The Efficacy and Safety of Biologics in Treating Ankylosing Spondylitis and Their Impact on Quality of Life and Comorbidities: A Literature Review. Cureus 2024. https://doi.org/10.7759/cureus.55459.

Wang R, Maksymowych WP. Targeting the Interleukin-23/Interleukin-17 Inflammatory Pathway: Successes and Failures in the Treatment of Axial Spondyloarthritis. Front Immunol 2021;12:715510. https://doi.org/10.3389/fimmu.2021.715510.

Khan M. Axial spondyloarthritis and ankylosing spondylitis. Oxford University Press; 2023.

Yin Y, Wang M, Liu M, Zhou E, Ren T, Chang X, He M, Zeng K, Guo Y, Wu J. Efficacy and safety of IL-17 inhibitors for the treatment of ankylosing spondylitis: a systematic review and meta-analysis. Arthritis Res Ther 2020;22:111. https://doi.org/10.1186/s13075-020-02208-w.

Paroli M, Caccavale R, Paroli MP, Spadea L, Accapezzato D. Janus Kinase Inhibitors: A New Tool for the Treatment of Axial Spondyloarthritis. IJMS 2023;24:1027. https://doi.org/10.3390/ijms24021027.

Weaver CT, Hatton RD, Mangan PR, Harrington LE. IL-17 Family Cytokines and the Expanding Diversity of Effector T Cell Lineages. Annu Rev Immunol 2007;25:821–52. https://doi.org/10.1146/annurev.immunol.25.022106.141557.

Li H, Tsokos GC. IL-23/IL-17 Axis in Inflammatory Rheumatic Diseases. Clinic Rev Allerg Immunol 2021;60:31–45. https://doi.org/10.1007/s12016-020-08823-4.

Deodhar A, Van Den Bosch F, Poddubnyy D, Maksymowych WP, Van Der Heijde D, Kim T-H, Kishimoto M, Blanco R, Duan Y, Li Y, Pangan AL, Wung P, Song I-H. Upadacitinib for the treatment of active non-radiographic axial spondyloarthritis (SELECT-AXIS 2): a randomised, double-blind, placebo-controlled, phase 3 trial. The Lancet 2022;400:369–79. https://doi.org/10.1016/S0140-6736(22)01212-0.

Correction. The Journal of Clinical Pharma 2020;60:551–551. https://doi.org/10.1002/jcph.1597.

Van Den Bosch F, Deodhar A, Poddubnyy D, Maksymowych WP, Van Der Heijde D, Kim T, Kishimoto M, Baraliakos X, Li Y, D’Silva K, Wung P, Song I. Upadacitinib in Active Non-radiographic Axial Spondyloarthritis: 1-Year Data From a Double-Blind , Randomized, Placebo-Controlled , Phase 3 Trial. ACR Open Rheumatology 2024;6:470–80. https://doi.org/10.1002/acr2.11669.

Deodhar A, Van Der Heijde D, Sieper J, Van Den Bosch F, Maksymowych WP, Kim T, Kishimoto M, Ostor A, Combe B, Sui Y, Chu AD, Song I. 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 & Rheumatology 2022;74:70–80. https://doi.org/10.1002/art.41911.

Li Z, Brown MA. Progress of genome-wide association studies of ankylosing spondylitis. Clin & Trans Imm 2017;6:e163. https://doi.org/10.1038/cti.2017.49.

International Genetics of Ankylosing Spondylitis Consortium (IGAS). Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci. Nat Genet 2013;45:730–8. https://doi.org/10.1038/ng.2667.

Brown MA, Wordsworth BP. Genetics in ankylosing spondylitis – Current state of the art and translation into clinical outcomes. Best Practice & Research Clinical Rheumatology 2017;31:763–76. https://doi.org/10.1016/j.berh.2018.09.005.

Kenyon M, Maguire S, Rueda Pujol A, O’Shea F, McManus R. The genetic backbone of ankylosing spondylitis: how knowledge of genetic susceptibility informs our understanding and management of disease. Rheumatol Int 2022;42:2085–95. https://doi.org/10.1007/s00296-022-05174-5.

Saveanu L, Carroll O, Lindo V, Del Val M, Lopez D, Lepelletier Y, Greer F, Schomburg L, Fruci D, Niedermann G, Van Endert PM. Concerted peptide trimming by human ERAP1 and ERAP2 aminopeptidase complexes in the endoplasmic reticulum. Nat Immunol 2005;6:689–97. https://doi.org/10.1038/ni1208.

Hanson AL, International Genetics of Ankylosing Spondylitis Consortium, Vukcevic D, Leslie S, Harris J, Lê Cao K-A, Kenna TJ, Brown MA. Epistatic interactions between killer immunoglobulin-like receptors and human leukocyte antigen ligands are associated with ankylosing spondylitis. PLoS Genet 2020;16:e1008906. https://doi.org/10.1371/journal.pgen.1008906.

Peruzzi M, Parker KC, Long EO, Malnati MS. Peptide sequence requirements for the recognition of HLA-B*2705 by specific natural killer cells. The Journal of Immunology 1996;157:3350–6. https://doi.org/10.4049/jimmunol.157.8.3350.

Forbes JD, Van Domselaar G, Bernstein CN. The Gut Microbiota in Immune-Mediated Inflammatory Diseases. Front Microbiol 2016;7. https://doi.org/10.3389/fmicb.2016.01081.

Taurog JD, Richardson JA, Croft JT, Simmons WA, Zhou M, Fernández-Sueiro JL, Balish E, Hammer RE. The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats. The Journal of Experimental Medicine 1994;180:2359–64. https://doi.org/10.1084/jem.180.6.2359.

Du X, Li H, Zhao H, Cui S, Sun X, Tan X. Causal relationship between gut microbiota and ankylosing spondylitis and potential mediating role of inflammatory cytokines: A mendelian randomization study. PLoS ONE 2024;19:e0306792. https://doi.org/10.1371/journal.pone.0306792.

Wang L, Wei Z, Pan F, Song C, Peng L, Yang Y, Huang F. Case report: Fecal microbiota transplantation in refractory ankylosing spondylitis. Front Immunol 2023;14:1093233. https://doi.org/10.3389/fimmu.2023.1093233.

Filidou E, Kandilogiannakis L, Shrewsbury A, Kolios G, Kotzampassi K. Probiotics: Shaping the gut immunological responses. World J Gastroenterol 2024;30:2096–108. https://doi.org/10.3748/wjg.v30.i15.2096.

Zhang L, Han R, Zhang X, Fang G, Chen J, Li J, Xu S, Qian L, Chen W, Pan F. Fecal microbiota in patients with ankylosing spondylitis: Correlation with dietary factors and disease activity. Clinica Chimica Acta 2019;497:189–96. https://doi.org/10.1016/j.cca.2019.07.038.

Li M, Dai B, Tang Y, Lei L, Li N, Liu C, Ge T, Zhang L, Xu Y, Hu Y, Li P, Zhang Y, Yuan J, Li X. Altered Bacterial-Fungal Interkingdom Networks in the Guts of Ankylosing Spondylitis Patients. mSystems 2019;4:e00176-18. https://doi.org/10.1128/mSystems.00176-18.

Wen C, Zheng Z, Shao T, Liu L, Xie Z, Le Chatelier E, He Z, Zhong W, Fan Y, Zhang L, Li H, Wu C, Hu C, Xu Q, Zhou J, Cai S, Wang D, Huang Y, Breban M, Qin N, Ehrlich SD. Quantitative metagenomics reveals unique gut microbiome biomarkers in ankylosing spondylitis. Genome Biol 2017;18:142. https://doi.org/10.1186/s13059-017-1271-6.

Mandl P, Navarro-Compán V, Terslev L, Aegerter P, Van Der Heijde D, D’Agostino MA, Baraliakos X, Pedersen SJ, Jurik AG, Naredo E, Schueller-Weidekamm C, Weber U, Wick MC, Bakker PAC, Filippucci E, Conaghan PG, Rudwaleit M, Schett G, Sieper J, Tarp S, Marzo-Ortega H, Østergaard M. EULAR recommendations for the use of imaging in the diagnosis and management of spondyloarthritis in clinical practice. Annals of the Rheumatic Diseases 2015;74:1327–39. https://doi.org/10.1136/annrheumdis-2014-206971.

Khmelinskii N, Regel A, Baraliakos X. The Role of Imaging in Diagnosing Axial Spondyloarthritis. Front Med 2018;5:106. https://doi.org/10.3389/fmed.2018.00106.

Ożga JK, Mężyk E, Kmiecik W, Wojciechowski W, Żuber Z. Magnetic resonance imaging of the musculoskeletal system in the diagnosis of rheumatic diseases in the pediatric population. Reumatologia 2024;62:196–206. https://doi.org/10.5114/reum/190262.

Østergaard M, Lambert RGW. Imaging in ankylosing spondylitis. Therapeutic Advances in Musculoskeletal 2012;4:301–11. https://doi.org/10.1177/1759720X11436240.

Matsubara K, Ibaraki M, Nemoto M, Watabe H, Kimura Y. A review on AI in PET imaging. Ann Nucl Med 2022;36:133–43. https://doi.org/10.1007/s12149-021-01710-8.

Artesani A, Bruno A, Gelardi F, Chiti A. Empowering PET: harnessing deep learning for improved clinical insight. Eur Radiol Exp 2024;8:17. https://doi.org/10.1186/s41747-023-00413-1.

Feng X, Qiao J, Xu W. Impact of immune regulation and differentiation dysfunction of mesenchymal stem cells on the disease process in ankylosing spondylitis and prospective analysis of stem cell transplantation therapy. Postgraduate Medical Journal 2023;99:1138–47. https://doi.org/10.1093/postmj/qgad073.

Aboul-Soud MAM, Alzahrani AJ, Mahmoud A. Induced Pluripotent Stem Cells (iPSCs)—Roles in Regenerative Therapies, Disease Modelling and Drug Screening. Cells 2021;10:2319. https://doi.org/10.3390/cells10092319.

Li A, Tao Y, Kong D, Zhang N, Wang Y, Wang Z, Wang Y, Wang J, Xiao J, Jiang Y, Liu X, Zheng C. Infusion of umbilical cord mesenchymal stem cells alleviates symptoms of ankylosing spondylitis. Experimental and Therapeutic Medicine 2017;14:1538–46. https://doi.org/10.3892/etm.2017.4687.

Dilip Kumar S, Aashabharathi M, KarthigaDevi G, Subbaiya R, Saravanan M. Insights of CRISPR-Cas systems in stem cells: progress in regenerative medicine. Mol Biol Rep 2022;49:657–73. https://doi.org/10.1007/s11033-021-06832-w.

Li Z-H, Wang J, Xu J-P, Wang J, Yang X. Recent advances in CRISPR-based genome editing technology and its applications in cardiovascular research. Military Med Res 2023;10:12. https://doi.org/10.1186/s40779-023-00447-x.