TY - JOUR
T1 - Efficacy and safety of biological DMARDs
T2 - a systematic literature review informing the 2022 update of the ASAS-EULAR recommendations for the management of axial spondyloarthritis
AU - Webers, Casper
AU - Ortolan, Augusta
AU - Sepriano, Alexandre
AU - Falzon, Louise
AU - Baraliakos, Xenofon
AU - Landewé, Robert B. M.
AU - Ramiro, Sofia
AU - van der Heijde, D. sirée
AU - Nikiphorou, Elena
N1 - Publisher Copyright: © Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2022/10/21
Y1 - 2022/10/21
N2 - 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.
AB - 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.
KW - axial spondyloarthritis
KW - biological therapy
KW - spondylitis, ankylosing
KW - tumour necrosis factor inhibitors
UR - http://www.scopus.com/inward/record.url?scp=85142050292&partnerID=8YFLogxK
U2 - https://doi.org/10.1136/ard-2022-223298
DO - https://doi.org/10.1136/ard-2022-223298
M3 - Review article
C2 - 36270657
SN - 0003-4967
VL - 82
SP - 130
EP - 141
JO - Annals of the rheumatic diseases
JF - Annals of the rheumatic diseases
IS - 1
M1 - A80
ER -