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Comparative Study
. 2025 Mar;39(2):297-306.
doi: 10.1007/s40259-025-00705-5. Epub 2025 Jan 29.

Interleukin-23 versus Interleukin-17 Inhibitors in Preventing Incidental Psoriatic Arthritis in Patients with Psoriasis: A Real-World Comparison From the TriNetX US Collaborative Network

Sebastian Yu #  1   2   3   4 , An-Ping Huo #  5   6   7 , Yu-Hsun Wang  8 , James Cheng-Chung Wei  9   10   11   12   13   14
Affiliations
Comparative Study

Interleukin-23 versus Interleukin-17 Inhibitors in Preventing Incidental Psoriatic Arthritis in Patients with Psoriasis: A Real-World Comparison From the TriNetX US Collaborative Network

Sebastian Yu et al. BioDrugs. 2025 Mar.

Abstract

Background: Psoriatic arthritis (PsA) is a common comorbidity in patients with psoriasis (PsO) that leads to significant disease burden. Biologic therapies targeting the interleukin (IL)-23/IL-17 axis have been widely used for PsO, but their comparative effectiveness in preventing PsA remains unclear.

Objective: The study objective was to compare the occurrence of developing incidental PsA among PsO patients treated with interleukin-23 inhibitors (IL23is) or interleukin-17 inhibitors (IL17is).

Methods: A retrospective cohort study was conducted using real-world data from the TriNetX US Collaborative Network, including 53 healthcare organizations. Adult PsO patients treated with IL23is or IL17is between January 2019 and June 2022 were identified. Cox regression analysis was used to assess the risk of PsA incidence, with hazard ratios (HRs) and 95% confidence intervals (CIs) reported. Subgroup analyses were performed based on age, sex, and ethnicity. Sensitivity analyses included comparisons with tumor necrosis factor (TNF) inhibitors (TNFis) to ensure robustness.

Results: A total of 4,580 PsO patients were included in the study, with 2,273 receiving IL23is and 2,307 receiving IL17is. Treatment with IL23is was associated with a significantly lower incidence of PsA compared to IL17is (HR = 0.60, 95% CI 0.44-0.82, P = 0.001). This reduction in risk was particularly notable in the 41- to 65-year age group (HR = 0.42, 95% CI 0.27-0.64, P < 0.001) and among females (HR = 0.57, 95% CI 0.38-0.86, P = 0.007). Subgroup analyses based on ethnicity revealed varying outcomes, with White patients showing a significant risk reduction (HR = 0.55, 95% CI 0.38-0.79, P = 0.001) but no significant risk reduction was observed in Black or African American patients (HR = 1.37, 95% CI 0.37-5.13, P = 0.637). Sensitivity analyses comparing IL23is and TNFis confirmed the robustness of the findings.

Conclusion: IL23is are associated with a lower risk of PsA incidence compared to IL17is in PsO patients, particularly in specific age, sex, and ethnic groups. These findings suggest that IL23is may be more suitable for PsO patients at high risk of PsA and could inform potential updates to treatment guidelines. Further research should focus on refining therapeutic strategies by incorporating patient-specific factors such as comorbidities, ethnicity, and genetic predispositions, which could optimize biologic selection and enhance PsA prevention efforts in clinical practice.

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Conflict of interest statement

Declarations. Funding information: This research was funded by a grant from the Taiwan National Science and Technology Council (NSTC-111-2314-B-037-042, NSTC-112-2221-E-020-005, and NSTC-113-2314-B-037-076-MY3) to S.Y. Conflicts of Interest Statement: None declared. Research Ethics Approval, Human Participants: TriNetX obtained a waiver from the Western Institutional Review Board (WIRB) due to its provision of aggregated counts and statistical summaries of de-identified data, adhering to the de-identification standards specified in Section §164.514(a) of the HIPAA Privacy Rule. This study was approved by Chung Shan Medical University Hospital Institutional Review Board (IRB NO: CS2-21176). Data availability Statement: The data that support the findings of this study are available from the corresponding author upon reasonable request. Patient and Public Involvement Statement: Patients or the public were not involved in the design, conduct, reporting, or dissemination plans of our research. Author Contributions: Conceptualization: Sebastian Yu, An-Ping Huo, James Cheng-Chung Wei. Methodology: Sebastian Yu, Yu-Hsun Wang, James Cheng-Chung Wei. Formal analysis and investigation: Sebastian Yu, Yu-Hsun Wang, James Cheng-Chung Wei. Writing – original draft preparation: Sebastian Yu, An-Ping Huo. Writing - review and editing: Yu-Hsun Wang, James Cheng-Chung Wei. Funding acquisition: Sebastian Yu, James Cheng-Chung Wei. Resources: James Cheng-Chung Wei. Supervision: James Cheng-Chung Wei.

Figures

Fig. 1
Fig. 1
Flow chart of the study design
Fig. 2
Fig. 2
Forest plot showing the hazard ratios (HRs) and 95% confidence intervals (CIs) associated with variables considered in the univariable analyses with time to the primary endpoint (psoriatic arthritis) as the dependent variable. Blocks represent HRs and horizontal bars extend from the lower limit to the upper limit of the 95% CI of the estimate of the HR. IL23is IL-23 inhibitors, IL17is IL-17 inhibitors
Fig. 3
Fig. 3
Cumulative incidence of psoriatic arthritis (PsA) between the IL17i and IL23i cohorts. The increase in the cumulative incidence of PsA in the IL23i cohort was significantly lower than in the IL17i cohort by Kaplan-Meier method estimates (P = 0.001). IL17is IL-17 inhibitors, IL23is IL-23 inhibitors
See this image and copyright information in PMC

References

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