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Efficacy and safety of biological DMARDs: a systematic literature review informing the 2022 update of the ASAS-EULAR recommendations for the management of axial spondyloarthritis
  1. Casper Webers1,2,
  2. Augusta Ortolan3,4,
  3. Alexandre Sepriano4,5,
  4. Louise Falzon6,
  5. Xenofon Baraliakos7,
  6. Robert B M Landewé8,9,
  7. Sofia Ramiro4,9,
  8. Désirée van der Heijde4,
  9. Elena Nikiphorou4,10,11
  1. 1Department of Internal Medicine, Division of Rheumatology, Maastricht University Medical Centre+, Maastricht, The Netherlands
  2. 2Care and Public Health Research Institute (CAPHRI), Maastricht University, Maastricht, The Netherlands
  3. 3Rheumatology Unit, Department of Medicine DIMED, University of Padua, Padua, Italy
  4. 4Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  5. 5NOVA Medical School, Universidade Nova de Lisboa, Lisboa, Portugal
  6. 6Health Economics and Decision Science, School of Health and Related Research, The University of Sheffield, Sheffield, UK
  7. 7Rheumazentrum Ruhrgebiet, Ruhr University Bochum, Herne, Germany
  8. 8Department of Clinical Immunology and Rheumatology, Amsterdam University Medical Centre, Amsterdam, The Netherlands
  9. 9Department of Rheumatology, Zuyderland Medical Centre Heerlen, Heerlen, The Netherlands
  10. 10Department of Rheumatology, King's College Hospital, London, UK
  11. 11Centre for Rheumatic Diseases, King's College London, London, UK
  1. Correspondence to Dr Casper Webers, Department of Internal Medicine, Division of Rheumatology, Maastricht University Medical Centre+, Postbus 5800, 6202AZ Maastricht, Limburg, The Netherlands; casper.webers{at}mumc.nl

Abstract

Objective To update the evidence on efficacy and safety of biological disease-modifying antirheumatic drugs (bDMARDs) in patients with axial spondyloarthritis (axSpA) to inform the 2022 update of the Assessment of SpondyloArthritis international Society/European Alliance of Associations for Rheumatology (ASAS-EULAR) recommendations for the management of axSpA.

Methods Systematic literature review (2016–2021) on efficacy and safety of bDMARDs in axSpA (radiographic axSpA (r-axSpA)/non-radiographic axSpA (nr-axSpA)). Eligible study designs included randomised controlled trials (RCTs), strategy trials and observational studies (the latter only for safety and extra-musculoskeletal manifestations). All relevant efficacy/safety outcomes were included.

Results In total, 148 publications were included. Efficacy of golimumab and certolizumab was confirmed. Tumour necrosis factor inhibitor (TNFi) biosimilar-originator equivalence was demonstrated. RCT (n=15) data on efficacy of interleukin-17 inhibitors (IL-17i) demonstrated clinically relevant effects (risk ratio vs placebo to achieve ASAS40 response 1.3–15.3 (r-axSpA, n=9), 1.4–2.1 (nr-axSpA, n=2)). Efficacy of secukinumab/ixekizumab was demonstrated in TNFi-naïve and TNFi-inadequate responders. IL-23 and IL-12/23 inhibitors (risankizumab/ustekinumab) failed to show relevant benefits. Tapering of TNFi by spacing was non-inferior to standard-dose treatment. The first axSpA treat-to-target trial did not meet its primary endpoint, but showed improvements in secondary outcomes. No new risks were identified with TNFi use in observational studies (data lacking for IL-17i). Secukinumab (n=1) and etanercept (n=2) were associated with increased risk of uveitis in observational studies compared to monoclonal TNFi.

Conclusions New evidence supports the efficacy and safety of TNFi (originators/biosimilars) and IL-17i in r-axSpA and nr-axSpA, while IL-23i failed to show relevant effects. Observational studies are needed to confirm long-term IL-17i safety.

PROSPERO registration number CRD42021257588

  • spondylitis, ankylosing
  • biological therapy
  • tumour necrosis factor inhibitors
  • axial spondyloarthritis

Data availability statement

All data relevant to this study are published in the article or in the supplemental files.

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Data availability statement

All data relevant to this study are published in the article or in the supplemental files.

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Footnotes

  • Handling editor Josef S Smolen

  • Twitter @AlexSepriano, @ElenaNikiUK

  • Contributors All authors contributed and finally approved the current manuscript.

  • Funding European Alliance of Associations for Rheumatology and Assessment of SpondyloArthritis international Society.

  • Competing interests CW, AO and LF 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 and UCB, and is an Editorial Board member of Annals of Rheumatic Diseases. RBML has received consulting fees from AbbVie, Bristol Myers Squibb, Celgene, Jansen, Galapagos, GlaxoSmithKline, Novartis, Pfizer and 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, GlaxoSmithKline, Janssen, Lilly, Novartis, Pfizer and UCB Pharma, and is Director of Imaging Rheumatology BV. 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.

  • Patient and public involvement statement The Task force on this project involved two patient research partners (Boryana Boteva and Mark Telkman), who participated in the Task force meeting where the results of this SLR were presented and discussed.

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

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.