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Efficacy and safety of biological and targeted-synthetic DMARDs: a systematic literature review informing the 2016 update of the ASAS/EULAR recommendations for the management of axial spondyloarthritis
  1. Alexandre Sepriano1,2,
  2. Andrea Regel3,
  3. Désirée van der Heijde4,
  4. Jürgen Braun3,
  5. Xenofon Baraliakos3,
  6. Robert Landewé5,6,
  7. Filip Van den Bosch7,
  8. Louise Falzon8 and
  9. Sofia Ramiro1
  1. 1Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2NOVA Medical School, Universidade Nova de Lisboa, Lisboa, Portugal
  3. 3Rheumazentrum Ruhrgebiet, Ruhr-University Bochum, Herne, Germany
  4. 4Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  5. 5Department of Clinical Immunology & Rheumatology, Amsterdam Rheumatology & Clinical Immunology Center, Amsterdam, The Netherlands
  6. 6Zuyderland Medical Center, Heerlen, The Netherlands
  7. 7Ghent University Hospital, Ghent, Belgium
  8. 8Center for Behavioral Cardiovascular Health, Columbia University Medical Center, New York, USA
  1. Correspondence to Dr Alexandre Sepriano; alexsepriano{at}


Objectives To update the evidence for the efficacy and safety of (b)biological and (ts)targeted-synthetic disease-modifying anti-rheumatic drugs (DMARDs) in patients with axial spondyloarthritis (axSpA) to inform the 2016 update of the Assessment of SpondyloArthritis international Society/European League Against Rheumatism (ASAS/EULAR) recommendations for the management of axSpA.

Methods Systematic literature review (2009–2016) for randomised controlled trials (RCT), including long-term extensions, strategy trials and observational studies (the latter was only for safety assessment and a comparator was required). Interventions were any bDMARD or tsDMARD. All relevant efficacy and safety outcomes were included.

Results 76 papers and 24 abstracts fulfilled the inclusion criteria. Large treatment effects were found both in radiographic axSpA (r-axSpA) and non-radiographic axSpA (nr-axSpA) for all tumour necrosis factor inhibitors (TNFi) (NNT to achieve ASAS40 response ranged between 2.6–5.2 for r-axSpA and 2.3–5.4 for nr-axSpA). For nr-axSpA, efficacy was superior for those who had objective signs of inflammation (positive C reactive protein or inflammation on MRI-SI). Secukinumab 150 mg has shown efficacy in two phase 3 RCTs (NNT to achieve ASAS40 response: 3.4 and 4.0). Ustekinumab and tofacitinib have shown positive results in phase 2/proof-of-concept trials; trials with apremilast, rituximab, interleukin (IL)-6 antagonists and abatacept have failed their primary end points. New (unknown) safety signals were not found in the trials but long-term observational safety data for TNFi are still scarce.

Conclusions New evidence supports the efficacy and safety of TNFi both in r-axSpA and nr-axSpA. Secukinumab is the first drug targeting the IL-17 pathway in r-axSpA that has shown efficacy.

  • Spondyloarthritis
  • DMARDs (biologic)
  • DMARDs (synthetic)
  • TNF-alpha
  • Treatment

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  • Funding Fundação para a Ciência e Tecnologia (Fundação para a Ciência e Tecnologia), European League Against Rheumatism, Assessment of SpondyloArthritis international Society.

  • Competing interests AS: Fundação para a Ciência e Tecnologia (grant number: SFRH/BD/108246/2015); AR: none; DvdH: AbbVie, Amgen, Astellas, AstraZeneca, Bristol Myers Squibb, Boeringer Ingelheim, Celgene, Daiichi, Eli-Lilly, Galapagos, Gilead, 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; XB: AbbVie, Bristol Myers Squibb, Celgene, Janssen, Novartis, Pfizer, Roche, MSD and UCB; 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; FVdB: AbbVie, BMS, Celgene, Janssen, Merck, Novartis, Pfizer and UCB; LF: none; SR: none.

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

  • Data sharing statement No additional data are available.

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