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

Casper Webers; Augusta Ortolan; Alexandre Sepriano; Louise Falzon; Xenofon Baraliakos; Robert B M Landewé; Sofia Ramiro; Désirée van der Heijde; Elena Nikiphorou

doi:10.1136/ard-2022-223298

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

Casper Webers^*, Augusta Ortolan, Alexandre Sepriano, Louise Falzon, Xenofon Baraliakos, Robert B M Landewé, Sofia Ramiro, Désirée van der Heijde, Elena Nikiphorou

^*Corresponding author for this work

Research output: Contribution to journal › (Systematic) Review article › peer-review

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Abstract

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.

Original language	English
Pages (from-to)	130-141
Number of pages	12
Journal	Annals of the Rheumatic Diseases
Volume	82
Issue number	1
Early online date	21 Oct 2022
DOIs	https://doi.org/10.1136/ard-2022-223298
Publication status	Published - Jan 2023

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Webers, C., Ortolan, A., Sepriano, A., Falzon, L., Baraliakos, X., Landewé, R. B. M., Ramiro, S., van der Heijde, D., & Nikiphorou, E. (2023). 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. Annals of the Rheumatic Diseases, 82(1), 130-141. https://doi.org/10.1136/ard-2022-223298

@article{19ca546176924604b808687b99d15c2d,

title = "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",

abstract = "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-na{\"i}ve 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.",

author = "Casper Webers and Augusta Ortolan and Alexandre Sepriano and Louise Falzon and Xenofon Baraliakos and Landew{\'e}, {Robert B M} and Sofia Ramiro and {van der Heijde}, D{\'e}sir{\'e}e and Elena Nikiphorou",

note = "{\textcopyright} Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.",

year = "2023",

month = jan,

doi = "10.1136/ard-2022-223298",

language = "English",

volume = "82",

pages = "130--141",

journal = "Annals of the Rheumatic Diseases",

issn = "0003-4967",

publisher = "BMJ Publishing Group",

number = "1",

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Webers, C, Ortolan, A, Sepriano, A, Falzon, L, Baraliakos, X, Landewé, RBM, Ramiro, S, van der Heijde, D & Nikiphorou, E 2023, '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', Annals of the Rheumatic Diseases, vol. 82, no. 1, pp. 130-141. https://doi.org/10.1136/ard-2022-223298

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. / Webers, Casper; Ortolan, Augusta; Sepriano, Alexandre et al.
In: Annals of the Rheumatic Diseases, Vol. 82, No. 1, 01.2023, p. 130-141.

Research output: Contribution to journal › (Systematic) Review article › peer-review

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, Désirée

AU - Nikiphorou, Elena

PY - 2023/1

Y1 - 2023/1

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.PROSPERO REGISTRATION NUMBER: CRD42021257588.

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.PROSPERO REGISTRATION NUMBER: CRD42021257588.

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DO - 10.1136/ard-2022-223298

M3 - (Systematic) 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

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