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Efficacy and safety of non-pharmacological and non-biological interventions: a systematic literature review informing the 2022 update of the ASAS/EULAR recommendations for the management of axial spondyloarthritis
  1. Augusta Ortolan1,2,
  2. Casper Webers3,4,
  3. Alexandre Sepriano1,5,
  4. Louise Falzon6,
  5. Xenofon Baraliakos7,
  6. Robert BM Landewé8,9,
  7. Sofia Ramiro1,9,
  8. Désirée van der Heijde1,
  9. Elena Nikiphorou1,10,11
  1. 1 Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2 Rheumatology Unit, Department of Medicine DIMED, University of Padova, Padova, Italy
  3. 3 Department of Internal Medicine, Division of Rheumatology, Maastricht University Medical Center, Maastricht, The Netherlands
  4. 4 Care and Public Health Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
  5. 5 Rheumatology, NOVA Medical School, Universidade Nova de Lisboa, Lisboa, Portugal
  6. 6 Health Economics and Decision Science, School of Health and Related Research, University of Sheffield, Sheffield, UK
  7. 7 Rheumazentrum Ruhrgebiet, Ruhr University Bochum, Herne, Germany
  8. 8 Department of Clinical Immunology and Rheumatology, Amsterdam University Medical Center, Duivendrecht, The Netherlands
  9. 9 Department of Rheumatology, Zuyderland Medical Center, Heerlen, The Netherlands
  10. 10 Department of Rheumatology, King's College Hospital, London, UK
  11. 11 Centre for Rheumatic Diseases, King's College London, London, UK
  1. Correspondence to Dr Augusta Ortolan, Department of Rheumatology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands; augusta.ortolan{at}


Objective To update the evidence of non-biological treatments for axial spondyloarthritis (axSpA), as a basis for the 2022 Assessment of SpondyloArthritis international Society-European Alliance of Associations for Rheumatology (ASAS-EULAR) recommendations for the management of axSpA.

Methods A systematic literature review (2016–2021) on efficacy and safety of non-pharmacological and non-biological pharmacological treatments was performed, up to 1 January 2022. The research question was formulated according to the PICO format: Population: adult patients with r-axSpA and nr-axSpA; Intervention: non-pharmacological and non-biological pharmacological treatments; Comparator: active comparator or placebo; Outcomes: all relevant efficacy and safety outcomes. Type of studies included were: randomised controlled trials (RCTs), observational studies (for efficacy of non-pharmacological treatments, and safety), qualitative studies. Cohen’s effect size (ES) was calculated for non-pharmacological and risk ratio (RR) for pharmacological treatments.

Results Of 107 publications included, 63 addressed non-pharmacological interventions, including education (n=8) and exercise (n=20). The ES for education on disease activity, function, mobility was small to moderate (eg. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), ES: 0.06–0.59). Exercise had moderate to high ES on these outcomes (eg. BASDAI, ES: 0.14–1.43). Six RCTs on targeted synthetic disease-modifying antirheumatic drugs (DMARDs) showed efficacy of tofacitinib, upadacitinib and filgotinib (phase 2 only) in r-axSpA (range RR vs placebo for ASAS20: 1.91–3.10), while apremilast and nilotinib were not efficacious. Studies on conventional synthetic DMARDs (n=3), non-steroidal anti-inflammatory drugs (NSAIDs, n=8) and other drugs (n=12) did not provide new evidence on efficacy/safety (efficacy of NSAIDs confirmed; limited efficacy of short-term glucocorticoids in one RCT).

Conclusions Education, exercise and NSAIDs confirmed to be efficacious in axSpA. JAKi were proved efficacious in r-axSpA.

  • Spondylitis, Ankylosing
  • Physical Therapy Modalities
  • Glucocorticoids
  • Anti-Inflammatory Agents, Non-Steroidal

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  • Handling editor Josef S Smolen

  • Twitter @AlexSepriano, @ElenaNikiUK

  • Contributors AO was responsible for acquisition, analysis and interpretation of data and drafted the manuscript. CW and LF participated in the acquisition, analysis and interpretation of data. AS, SR, DvDH and EN were responsible for the conception and design of the work, and revised it critically for important intellectual content. RL and XB made substantial contributions to the design of the work, and revised it critically for important intellectual content. All the authors approved the final version of this article.

  • Funding This study was funded by European Alliance of Associations for Rheumatology, Assessment of SpondyloArthritis international Society.

  • Competing interests CW and AO have nothing to declare. AS has received speaker/consulting fees from UCB and Novartis. XB received consulting fees and research grants from Abbvie, BMS, Eli-Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB and is an Editorial Board member of Annals of Rheumatic Diseases. RL is EULAR Council member and chair of Quality of Care, has received consulting fees from AbbVie, Bristol Myers Squibb, Jansen, Galapagos, Gilead, Glaxo-Smith-Kline, Novartis, Pfizer, UCB and is Director of Rheumatology Consultancy BV. SR received research grants from AbbVie, Galapagos, Novartis, Pfizer and UCB, and consulting fees from AbbVie, Eli Lilly, Novartis, MSD, Pfizer, UCB and Sanofi. DvdH received consulting fees from AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Novartis, Pfizer, UCB Pharma and is Director of Imaging Rheumatology BV. She is associate editor of Annals of Rheumatic Diseases and Editorial Board member of Journal of Rheumatology. EN has received speaker honoraria/participated in advisory boards for Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, Lilly and holds research grants from Pfizer and Lilly.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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