Efficacy and safety of non-pharmacological and non-biological pharmacological treatment: a systematic literature review informing the 2016 update of the ASAS/EULAR recommendations for the management of axial spondyloarthritis

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.