Efficacy and safety of biological DMARDs: a systematic literature review informing the 2022 update of the ASAS-EULAR recommendations for the management of axial spondyloarthritis

Ann Rheum Dis. 2023 Jan;82(1):130-141. doi: 10.1136/ard-2022-223298. Epub 2022 Oct 21.


Objective: To update the evidence on efficacy and safety of biological disease-modifying antirheumatic drugs (bDMARDs) in patients with axial spondyloarthritis (axSpA) to inform the 2022 update of the Assessment of SpondyloArthritis international Society/European Alliance of Associations for Rheumatology (ASAS-EULAR) recommendations for the management of axSpA.

Methods: Systematic literature review (2016-2021) on efficacy and safety of bDMARDs in axSpA (radiographic axSpA (r-axSpA)/non-radiographic axSpA (nr-axSpA)). Eligible study designs included randomised controlled trials (RCTs), strategy trials and observational studies (the latter only for safety and extra-musculoskeletal manifestations). All relevant efficacy/safety outcomes were included.

Results: In total, 148 publications were included. Efficacy of golimumab and certolizumab was confirmed. Tumour necrosis factor inhibitor (TNFi) biosimilar-originator equivalence was demonstrated. RCT (n=15) data on efficacy of interleukin-17 inhibitors (IL-17i) demonstrated clinically relevant effects (risk ratio vs placebo to achieve ASAS40 response 1.3-15.3 (r-axSpA, n=9), 1.4-2.1 (nr-axSpA, n=2)). Efficacy of secukinumab/ixekizumab was demonstrated in TNFi-naïve and TNFi-inadequate responders. IL-23 and IL-12/23 inhibitors (risankizumab/ustekinumab) failed to show relevant benefits. Tapering of TNFi by spacing was non-inferior to standard-dose treatment. The first axSpA treat-to-target trial did not meet its primary endpoint, but showed improvements in secondary outcomes. No new risks were identified with TNFi use in observational studies (data lacking for IL-17i). Secukinumab (n=1) and etanercept (n=2) were associated with increased risk of uveitis in observational studies compared to monoclonal TNFi.

Conclusions: New evidence supports the efficacy and safety of TNFi (originators/biosimilars) and IL-17i in r-axSpA and nr-axSpA, while IL-23i failed to show relevant effects. Observational studies are needed to confirm long-term IL-17i safety.

Prospero registration number: CRD42021257588.

Keywords: axial spondyloarthritis; biological therapy; spondylitis, ankylosing; tumour necrosis factor inhibitors.

Publication types

  • Systematic Review
  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antirheumatic Agents* / therapeutic use
  • Axial Spondyloarthritis*
  • Biosimilar Pharmaceuticals* / adverse effects
  • Certolizumab Pegol / therapeutic use
  • Humans
  • Non-Radiographic Axial Spondyloarthritis*
  • Spondylarthritis* / chemically induced
  • Spondylarthritis* / drug therapy
  • Spondylitis, Ankylosing* / drug therapy
  • Treatment Outcome
  • Tumor Necrosis Factor Inhibitors / therapeutic use


  • Antirheumatic Agents
  • Certolizumab Pegol
  • Biosimilar Pharmaceuticals
  • Tumor Necrosis Factor Inhibitors