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Efficacy and safety of non-pharmacological and non-biological pharmacological treatment: a systematic literature review informing the 2016 update of the ASAS/EULAR recommendations for the management of axial spondyloarthritis
  1. Andrea Regel1,
  2. Alexandre Sepriano2,3,
  3. Xenofon Baraliakos1,
  4. Désirée van der Heijde2,
  5. Jürgen Braun1,
  6. Robert Landewé4,5,
  7. Filip Van den Bosch6,
  8. Louise Falzon7 and
  9. Sofia Ramiro2
  1. 1Rheumazentrum Ruhrgebiet, Ruhr-University Bochum, Herne, Germany
  2. 2Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  3. 3NOVA Medical School, Universidade Nova de Lisboa, Lisbon, Portugal
  4. 4Department of Clinical Immunology & Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  5. 5Zuyderland Medical Center, Heerlen, The Netherlands
  6. 6Ghent University Hospital, Ghent, Belgium
  7. 7Center for Behavioral Cardiovascular Health, Columbia University Medical Center, New York, New York, USA
  1. Correspondence to Dr Sofia Ramiro; sofiaramiro{at}


To assess the efficacy and safety of non-biological therapies in patients with axial spondyloarthritis (axSpA) to inform the update of the Assessment of SpondyloArthritis international Society (ASAS)/European League Against Rheumatism (EULAR) recommendations for the management of axSpA. A systematic literature review (2009–2016) of all non-pharmacological treatments, non-biological drugs (except targeted synthetic disease-modifying antirheumatic drugs (DMARDs)) and surgical therapies was performed. Randomised controlled trials (RCTs) and clinical controlled trials were assessed for efficacy and safety, while observational studies with a comparator were assessed for safety. All relevant efficacy and safety outcomes were included. Study heterogeneity precluded data pooling. If possible, Cohen's effect size was calculated for non-pharmacological treatments. In total, 45 papers and 2 abstracts were included. Studies on non-pharmacological treatments were very heterogeneous but overall confirmed a benefit for regular exercises, with small improvements in disease activity, function and spinal mobility. New studies on non-steroidal anti-inflammatory drugs (NSAIDs) confirmed their efficacy and new safety signals were not found. NSAIDs used continuously compared with on-demand did not reduce the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) mean change over 2 years in patients with ankylosing spondylitis with normal C reactive protein (CRP; ≤5 mg/L) (1 ‘negative’ RCT (0.9 vs 0.8; p=0.62)), while for patients with high CRP, conflicting results were found (1 ‘positive’ RCT (0.2 vs 1.7; p=0.003), 1 ‘negative’ RCT (1.68 vs 0.96; p=0.28)). No new trials were found for conventional synthetic DMARDs (csDMARDs). Short-term high-dose systemic glucocorticoids showed limited efficacy. Regular exercises may improve several outcomes. Efficacy and safety of NSAIDs in axSpA are confirmed. Glucocorticoids are not proven to be effective in axSpA and new data on csDMARDs are lacking.

  • Spondyloarthritis
  • Treatment
  • Ankylosing Spondylitis

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  • Correction notice This article has been corrected since it was first published online.

  • Funding The study was funded by the European League Against Rheumatism (EULAR), and the Assessment of SpondyloArthritis international Society (ASAS).

  • Competing interests AS: Fundação para a Ciência e Tecnologia (grant number: SFRH/BD/108246/2015). XB: AbbVie, BMS, Boehringer Ingelheim, Celgene, Centocor, Chugai, Janssen Biologics, Novartis, Pfizer, UCB. DvdH: AbbVie, Amgen, Astellas, AstraZeneca, Bristol Myers Squibb, Boeringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Janssen, Merk, Novartis, Pfizer, Roche, Sanofi-Aventis, UCB, Imaging Rheumatology BV. JB: Abbott, Bristol Myers Squibb, Celgene, Celltrion, Chugai, Johnson & Johnson, MSD, Novartis, Pfizer, Roche, UCB Pharma. RL: Abbott/AbbVie, Ablynx, Amgen, AstraZeneca, BMS, Centocor, Janssen (formerly Centocor), GSK, Merck, Novo-Nordisk, Novartis, Pfizer, Roche, Schering-Plough, TiGenics UCB, Wyeth, Director of Rheumatology Consultancy BV. FdVB: AbbVie, Celgene, Janssen, Merck, Novartis, Pizer and UCB.

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

  • Data sharing statement No additional data are available.

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