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.
OBJECTIVE
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.
Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands; NOVA Medical School, Universidade Nova de Lisboa, Lisboa, Portugal.
Alexandre
0000-0003-1954-0229
A
Sepriano
Rheumazentrum Ruhrgebiet, Ruhr-University Bochum , Herne , Germany.
Andrea
A
Regel
Department of Rheumatology , Leiden University Medical Center , Leiden , The Netherlands.
Désirée
D
van der Heijde
Rheumazentrum Ruhrgebiet, Ruhr-University Bochum , Herne , Germany.
Jürgen
J
Braun
Rheumazentrum Ruhrgebiet, Ruhr-University Bochum , Herne , Germany.
Xenofon
X
Baraliakos
Department of Clinical Immunology & Rheumatology, Amsterdam Rheumatology & Clinical Immunology Center, Amsterdam, The Netherlands; Zuyderland Medical Center, Heerlen, The Netherlands.
Robert
R
Landewé
Ghent University Hospital , Ghent , Belgium.
Filip
F
Van den Bosch
Center for Behavioral Cardiovascular Health , Columbia University Medical Center , New York , USA.
Louise
L
Falzon
Department of Rheumatology , Leiden University Medical Center , Leiden , The Netherlands.
Sofia
S
Ramiro
DMARDs (biologic); DMARDs (synthetic); Spondyloarthritis; TNF-alpha; Treatment