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. 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

Alexandre Sepriano  1 , Andrea Regel  2 , Désirée van der Heijde  3 , Jürgen Braun  2 , Xenofon Baraliakos  2 , Robert Landewé  4 , Filip Van den Bosch  5 , Louise Falzon  6 , Sofia Ramiro  3
Affiliations

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

Alexandre Sepriano et al. RMD Open. .

Abstract

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.

Keywords: DMARDs (biologic); DMARDs (synthetic); Spondyloarthritis; TNF-alpha; Treatment.

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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.

Comment in

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