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RMD Open. 2017 Jan 27;3(1):e000396. doi: 10.1136/rmdopen-2016-000396. eCollection 2017.

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.

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Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands; NOVA Medical School, Universidade Nova de Lisboa, Lisboa, Portugal.
Rheumazentrum Ruhrgebiet, Ruhr-University Bochum , Herne , Germany.
Department of Rheumatology , Leiden University Medical Center , Leiden , The Netherlands.
Department of Clinical Immunology & Rheumatology, Amsterdam Rheumatology & Clinical Immunology Center, Amsterdam, The Netherlands; Zuyderland Medical Center, Heerlen, The Netherlands.
Ghent University Hospital , Ghent , Belgium.
Center for Behavioral Cardiovascular Health , Columbia University Medical Center , New York , USA.



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.


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.


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.


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.


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

Conflict of interest statement

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.

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