Incidence of Uveitis in Patients With Axial Spondylarthritis Treated With Biologics or Targeted Synthetics: A Systematic Review and Network Meta-Analysis

Katie Bechman; Zijing Yang; Maryam Adas; Deepak Nagra; Ali S. Uğuzlar; Mark D. Russell; Nicky Wilson; Sophia Steer; Sam Norton; James Galloway

doi:10.1002/art.42788

Incidence of Uveitis in Patients With Axial Spondylarthritis Treated With Biologics or Targeted Synthetics: A Systematic Review and Network Meta-Analysis

Katie Bechman^*, Zijing Yang, Maryam Adas, Deepak Nagra, Ali S. Uğuzlar, Mark D. Russell, Nicky Wilson, Sophia Steer, Sam Norton, James Galloway

^*Corresponding author for this work

King's College London

Research output: Contribution to journal › Article › peer-review

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Abstract

Objective

Anterior uveitis is a common extra-articular manifestation of axial spondyloarthritis (AxSpA). We set to evaluate the risk of anterior uveitis (AU) with biologics and synthetic disease-modifying drugs in AxSpA.

Methods

We conducted a systematic review and meta-analysis to identify phase II/III double-blinded randomized controlled trials of anti–tumor necrosis factor (TNF) monoclonal antibodies (mAb), anti–interleukin-17 (anti–IL-17), and Janus kinase inhibitors (JAKi) in AxSpA. Patient-exposure years (PEY) were calculated using the per-protocol approach. Incidence rate (IR) of AU/100 person-years were calculated by treatment group using the random effects approach. Network meta-analysis (NMA) was used to estimate risk of AU in treatment groups, expressed as IR ratios (IRRs). Bias was assessed using the Cochrane Risk of Bias-2 tool.

Results

Forty-four trials were included: 17 anti-TNF mAb (1,004 PEY), 9 etanercept (180 PEY), 13 anti–IL-17 (1,834 PEY), and 6 JAKi (331 PEY). The IR of AU were as follows for anti-TNF mAb: 4.1, 95% confidence interval (CI) 0–8.5; etanercept: 5.4, 95% CI 0–16.0; anti–IL-17: 2.8, 95% CI 1.6–4.1; JAKi: 1.5, 95% CI 0.0–3.0; and placebo: 10.8, 95% CI 7.4–14.1. In NMA, IRRs of treatments compared with placebo were as follows for anti-TNF mAb: 0.32, 95% CI 0.10–1.04; etanercept 0.42, 95% CI 0.08–2.38; anti–IL-17: 0.43, 95% CI 0.19–0.98; and JAKi: 0.32, 95% CI 0.06–1.67. Comparisons between anti-TNF mAb, anti–IL-17, and JAKi did not demonstrate any significant difference in AU risk. Using the surface under the cumulative ranking curve approach to rank AU risk, anti-TNF mAbs were associated with the lowest risk followed by JAKi, anti–IL-17, and etanercept. All treatments were ranked superior to placebo.

Conclusion

Anti-TNF mAbs, JAKi, and anti–IL-17 appear protective against AU events in individuals with AxSpA, with no significant differences in risk of AU between treatments.

Original language	English
Pages (from-to)	704-714
Number of pages	11
Journal	Arthritis and Rheumatology
Volume	76
Issue number	5
Early online date	13 Apr 2024
DOIs	https://doi.org/10.1002/art.42788
Publication status	Published - May 2024

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Incidence of Uveitis in_BECHMAN_Publishedonline13April2024_GOLD_VoR (CC BY)Final published version, 483 KBLicence: CC BY

Cite this

@article{fe1c4db6967e45f5beea21cfdcd53c77,

title = "Incidence of Uveitis in Patients With Axial Spondylarthritis Treated With Biologics or Targeted Synthetics: A Systematic Review and Network Meta-Analysis",

abstract = "ObjectiveAnterior uveitis is a common extra-articular manifestation of axial spondyloarthritis (AxSpA). We set to evaluate the risk of anterior uveitis (AU) with biologics and synthetic disease-modifying drugs in AxSpA.MethodsWe conducted a systematic review and meta-analysis to identify phase II/III double-blinded randomized controlled trials of anti–tumor necrosis factor (TNF) monoclonal antibodies (mAb), anti–interleukin-17 (anti–IL-17), and Janus kinase inhibitors (JAKi) in AxSpA. Patient-exposure years (PEY) were calculated using the per-protocol approach. Incidence rate (IR) of AU/100 person-years were calculated by treatment group using the random effects approach. Network meta-analysis (NMA) was used to estimate risk of AU in treatment groups, expressed as IR ratios (IRRs). Bias was assessed using the Cochrane Risk of Bias-2 tool.ResultsForty-four trials were included: 17 anti-TNF mAb (1,004 PEY), 9 etanercept (180 PEY), 13 anti–IL-17 (1,834 PEY), and 6 JAKi (331 PEY). The IR of AU were as follows for anti-TNF mAb: 4.1, 95% confidence interval (CI) 0–8.5; etanercept: 5.4, 95% CI 0–16.0; anti–IL-17: 2.8, 95% CI 1.6–4.1; JAKi: 1.5, 95% CI 0.0–3.0; and placebo: 10.8, 95% CI 7.4–14.1. In NMA, IRRs of treatments compared with placebo were as follows for anti-TNF mAb: 0.32, 95% CI 0.10–1.04; etanercept 0.42, 95% CI 0.08–2.38; anti–IL-17: 0.43, 95% CI 0.19–0.98; and JAKi: 0.32, 95% CI 0.06–1.67. Comparisons between anti-TNF mAb, anti–IL-17, and JAKi did not demonstrate any significant difference in AU risk. Using the surface under the cumulative ranking curve approach to rank AU risk, anti-TNF mAbs were associated with the lowest risk followed by JAKi, anti–IL-17, and etanercept. All treatments were ranked superior to placebo.ConclusionAnti-TNF mAbs, JAKi, and anti–IL-17 appear protective against AU events in individuals with AxSpA, with no significant differences in risk of AU between treatments.",

author = "Katie Bechman and Zijing Yang and Maryam Adas and Deepak Nagra and {S. Uğuzlar}, Ali and Russell, {Mark D.} and Nicky Wilson and Sophia Steer and Sam Norton and James Galloway",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.",

year = "2024",

month = may,

doi = "10.1002/art.42788",

language = "English",

volume = "76",

pages = "704--714",

journal = "Arthritis and Rheumatology",

issn = "2326-5191",

publisher = "Wiley",

number = "5",

}

TY - JOUR

T1 - Incidence of Uveitis in Patients With Axial Spondylarthritis Treated With Biologics or Targeted Synthetics

T2 - A Systematic Review and Network Meta-Analysis

AU - Bechman, Katie

AU - Yang, Zijing

AU - Adas, Maryam

AU - Nagra, Deepak

AU - S. Uğuzlar, Ali

AU - Russell, Mark D.

AU - Wilson, Nicky

AU - Steer, Sophia

AU - Norton, Sam

AU - Galloway, James

PY - 2024/5

Y1 - 2024/5

N2 - ObjectiveAnterior uveitis is a common extra-articular manifestation of axial spondyloarthritis (AxSpA). We set to evaluate the risk of anterior uveitis (AU) with biologics and synthetic disease-modifying drugs in AxSpA.MethodsWe conducted a systematic review and meta-analysis to identify phase II/III double-blinded randomized controlled trials of anti–tumor necrosis factor (TNF) monoclonal antibodies (mAb), anti–interleukin-17 (anti–IL-17), and Janus kinase inhibitors (JAKi) in AxSpA. Patient-exposure years (PEY) were calculated using the per-protocol approach. Incidence rate (IR) of AU/100 person-years were calculated by treatment group using the random effects approach. Network meta-analysis (NMA) was used to estimate risk of AU in treatment groups, expressed as IR ratios (IRRs). Bias was assessed using the Cochrane Risk of Bias-2 tool.ResultsForty-four trials were included: 17 anti-TNF mAb (1,004 PEY), 9 etanercept (180 PEY), 13 anti–IL-17 (1,834 PEY), and 6 JAKi (331 PEY). The IR of AU were as follows for anti-TNF mAb: 4.1, 95% confidence interval (CI) 0–8.5; etanercept: 5.4, 95% CI 0–16.0; anti–IL-17: 2.8, 95% CI 1.6–4.1; JAKi: 1.5, 95% CI 0.0–3.0; and placebo: 10.8, 95% CI 7.4–14.1. In NMA, IRRs of treatments compared with placebo were as follows for anti-TNF mAb: 0.32, 95% CI 0.10–1.04; etanercept 0.42, 95% CI 0.08–2.38; anti–IL-17: 0.43, 95% CI 0.19–0.98; and JAKi: 0.32, 95% CI 0.06–1.67. Comparisons between anti-TNF mAb, anti–IL-17, and JAKi did not demonstrate any significant difference in AU risk. Using the surface under the cumulative ranking curve approach to rank AU risk, anti-TNF mAbs were associated with the lowest risk followed by JAKi, anti–IL-17, and etanercept. All treatments were ranked superior to placebo.ConclusionAnti-TNF mAbs, JAKi, and anti–IL-17 appear protective against AU events in individuals with AxSpA, with no significant differences in risk of AU between treatments.

AB - ObjectiveAnterior uveitis is a common extra-articular manifestation of axial spondyloarthritis (AxSpA). We set to evaluate the risk of anterior uveitis (AU) with biologics and synthetic disease-modifying drugs in AxSpA.MethodsWe conducted a systematic review and meta-analysis to identify phase II/III double-blinded randomized controlled trials of anti–tumor necrosis factor (TNF) monoclonal antibodies (mAb), anti–interleukin-17 (anti–IL-17), and Janus kinase inhibitors (JAKi) in AxSpA. Patient-exposure years (PEY) were calculated using the per-protocol approach. Incidence rate (IR) of AU/100 person-years were calculated by treatment group using the random effects approach. Network meta-analysis (NMA) was used to estimate risk of AU in treatment groups, expressed as IR ratios (IRRs). Bias was assessed using the Cochrane Risk of Bias-2 tool.ResultsForty-four trials were included: 17 anti-TNF mAb (1,004 PEY), 9 etanercept (180 PEY), 13 anti–IL-17 (1,834 PEY), and 6 JAKi (331 PEY). The IR of AU were as follows for anti-TNF mAb: 4.1, 95% confidence interval (CI) 0–8.5; etanercept: 5.4, 95% CI 0–16.0; anti–IL-17: 2.8, 95% CI 1.6–4.1; JAKi: 1.5, 95% CI 0.0–3.0; and placebo: 10.8, 95% CI 7.4–14.1. In NMA, IRRs of treatments compared with placebo were as follows for anti-TNF mAb: 0.32, 95% CI 0.10–1.04; etanercept 0.42, 95% CI 0.08–2.38; anti–IL-17: 0.43, 95% CI 0.19–0.98; and JAKi: 0.32, 95% CI 0.06–1.67. Comparisons between anti-TNF mAb, anti–IL-17, and JAKi did not demonstrate any significant difference in AU risk. Using the surface under the cumulative ranking curve approach to rank AU risk, anti-TNF mAbs were associated with the lowest risk followed by JAKi, anti–IL-17, and etanercept. All treatments were ranked superior to placebo.ConclusionAnti-TNF mAbs, JAKi, and anti–IL-17 appear protective against AU events in individuals with AxSpA, with no significant differences in risk of AU between treatments.

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U2 - 10.1002/art.42788

DO - 10.1002/art.42788

M3 - Article

C2 - 38116697

AN - SCOPUS:85190771723

SN - 2326-5191

VL - 76

SP - 704

EP - 714

JO - Arthritis and Rheumatology

JF - Arthritis and Rheumatology

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Incidence of Uveitis in Patients With Axial Spondylarthritis Treated With Biologics or Targeted Synthetics: A Systematic Review and Network Meta-Analysis

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