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

Abstract

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.

Biologic therapy and spinal radiographic progression in patients with axial spondyloarthritis: A structured literature review

“…56 These findings have resulted in the development of targeted therapies aimed at inhibiting these inflammatory cytokines. However, although the clinical efficacy of biologic treatment has been established in patients with axSpA, [16][17][18] their impact on spinal radiographic progression has proven more difficult to establish. 17,19 The duration of biologic treatment is an important factor in assessing its effect on spinal progression in axSpA.…”

Sacroiliac joint variation associated with diffuse idiopathic skeletal hyperostosis

“…Typical findings of the SI joint in AS include sacroiliitis including joint erosions, joint space narrowing, sclerosis, and intraarticular ankylosis, but none of these are common in DISH [8,12]. According to recent progress in the treatment of SpA using biological disease-modifying antirheumatic drugs, including tumor necrosis factor inhibitors (TNFi) and interleukin 17 inhibitors (IL-17i) [28,29], early diagnosis facilitates timely treatment and may minimize structural damage. The present findings may thus contribute to an understanding of radiographic changes in the SI joint associated with DISH and sacroiliitis from SpA.…”

Inequity in biological DMARD prescription for spondyloarthritis across the globe: results from the ASAS-COMOSPA study

“…The csDMARD findings are supportive of the bDMARD results, highlighting that higher country welfare seems to be associated with higher bDMARD use (although not reaching statistical significance), independent of all other characteristics including country of residence, and with lower csDMARD use. Given the lack of evidence for efficacy of csDMARDs in axSpA1 and the available evidence consistently showing no efficacy,2–6 this reflects an unjust selection of treatment for patients in countries of lower socioeconomic welfare, based on decisions other than clinical indication. bDMARD use was almost double in countries with higher compared with lower country health expenditures.…”

“…The role of biological disease-modifying antirheumatic drugs (bDMARDs) in spondyloarthritis (SpA) has been extensively studied, and robust scientific evidence supports their efficacy in reducing disease activity and improving functional ability, spinal mobility and quality of life 1. bDMARDs are therefore recommended for use in the presence of active disease and following failure of two non-steroidal anti-inflammatory drugs (NSAIDs) 2.…”

“…Currently, there is a general lack of evidence on their role in axial spondyloarthritis (axSpA),1 and the existing evidence consistently shows no efficacy,3–5 making their role debatable6 and resulting in the Assessment in SpondyloArthritis international Society (ASAS) and the European League Against Rheumatism not supporting their use in patients with only axial disease 2…”