To update and integrate the recommendations for ankylosing spondylitis and the recommendations for the use of tumour necrosis factor inhibitors (TNFi) in axial spondyloarthritis (axSpA) into one set applicable to the full spectrum of patients with axSpA. Following the latest version of the European League Against Rheumatism (EULAR) Standardised Operating Procedures, two systematic literature reviews first collected the evidence regarding all treatment options (pharmacological and non-pharmacological) that were published since 2009. After a discussion of the results in the steering group and presentation to the task force, overarching principles and recommendations were formulated, and consensus was obtained by informal voting. A total of 5 overarching principles and 13 recommendations were agreed on. The first three recommendations deal with personalised medicine including treatment target and monitoring. Recommendation 4 covers non-pharmacological management. Recommendation 5 describes the central role of non-steroidal anti-inflammatory drugs (NSAIDs) as first-choice drug treatment. Recommendations 6-8 define the rather modest role of analgesics, and disprove glucocorticoids and conventional synthetic disease-modifying antirheumatic drugs (DMARDs) for axSpA patents with predominant axial involvement. Recommendation 9 refers to biological DMARDs (bDMARDs) including TNFi and IL-17 inhibitors (IL-17i) for patients with high disease activity despite the use (or intolerance/contraindication) of at least two NSAIDs. In addition, they should either have an elevated C reactive protein and/or definite inflammation on MRI and/or radiographic evidence of sacroiliitis. Current practice is to start with a TNFi. Switching to another TNFi or an IL-17i is recommended in case TNFi fails (recommendation 10). Tapering, but not stopping a bDMARD, can be considered in patients in sustained remission (recommendation 11). The final two recommendations (12, 13) deal with surgery and spinal fractures. The 2016 Assessment of SpondyloArthritis international Society-EULAR recommendations provide up-to-date guidance on the management of patients with axSpA

ObjectivesTo 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.MethodsSystematic 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.Results76 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.ConclusionsNew 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.

To assess the efficacy and safety of non-biological therapies in patients with axial spondyloarthritis (axSpA) to inform the update of the Assessment of SpondyloArthritis international Society (ASAS)/European League Against Rheumatism (EULAR) recommendations for the management of axSpA. A systematic literature review (2009–2016) of all non-pharmacological treatments, non-biological drugs (except targeted synthetic disease-modifying antirheumatic drugs (DMARDs)) and surgical therapies was performed. Randomised controlled trials (RCTs) and clinical controlled trials were assessed for efficacy and safety, while observational studies with a comparator were assessed for safety. All relevant efficacy and safety outcomes were included. Study heterogeneity precluded data pooling. If possible, Cohen's effect size was calculated for non-pharmacological treatments. In total, 45 papers and 2 abstracts were included. Studies on non-pharmacological treatments were very heterogeneous but overall confirmed a benefit for regular exercises, with small improvements in disease activity, function and spinal mobility. New studies on non-steroidal anti-inflammatory drugs (NSAIDs) confirmed their efficacy and new safety signals were not found. NSAIDs used continuously compared with on-demand did not reduce the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) mean change over 2 years in patients with ankylosing spondylitis with normal C reactive protein (CRP; ≤5 mg/L) (1 ‘negative’ RCT (0.9 vs 0.8; p=0.62)), while for patients with high CRP, conflicting results were found (1 ‘positive’ RCT (0.2 vs 1.7; p=0.003), 1 ‘negative’ RCT (1.68 vs 0.96; p=0.28)). No new trials were found for conventional synthetic DMARDs (csDMARDs). Short-term high-dose systemic glucocorticoids showed limited efficacy. Regular exercises may improve several outcomes. Efficacy and safety of NSAIDs in axSpA are confirmed. Glucocorticoids are not proven to be effective in axSpA and new data on csDMARDs are lacking.