Risk of Major Adverse Cardiovascular Events and Venous Thromboembolic Events Between Patients With Psoriasis or Psoriatic Arthritis on Tumor Necrosis Factor Inhibitors, Interleukin-17 Inhibitors, Interleukin-12/23 Inhibitors and Interleukin-23 Inhibitors: An Emulated Target Trial Analysis.

Abstract

Background: The risk of major adverse cardiovascular events (MACE) and venous thromboembolic events (VTE) in patients with psoriatic disease receiving biologics is not fully understood.

Objective: This study aimed to investigate whether novel biologic therapies (IL-17, IL-12/23, and IL-23 inhibitors) for biologic-naïve patients with psoriasis or psoriatic arthritis (PsA) are associated with differences in the risks of MACE and VTE compared with those with TNF inhibitors.

Methods: An emulated target trial was designed by a nationwide cohort using data from the TriNetX Research Network. Biologic-naïve patients with psoriasis or PsA receiving biologics between 2014 and 2022 were enrolled. Treatment groups were determined by patients' first prescription of biologics. Three propensity-matched cohorts were established, namely, IL-17i vs. TNFi, IL-12/23i vs. TNFi, and IL-23i vs. TNFi. The incidence rate and incidence rate ratios were estimated.

Results: A total of 32,098 biologic-naïve patients with psoriasis or PsA treated with biologics were included. All enrollees were further categorized into four cohorts (20,314 in the TNFi cohort, 5,073 in the IL-17i cohort, 3,573 in the IL-12/23i cohort, and 3,138 in the IL-23i cohort). No significant difference in the risks of MACE and VTE between biologics existed among patients with psoriatic disease. In the subgroup analyses for either psoriasis or PsA, no significant difference in the risks of MACE or VTE was noted among all comparisons in the subgroup. Among patients with pre-existing hyperlipidemia and diabetes mellitus, the risks of MACE and VTE among patients using new biologics (IL-17i, IL-12/23i, or IL-23i) were lower than those using TNFi.

Limitations: The data lack psoriasis severity.

Conclusion: Among patients with psoriasis or PsA, no significant risk differences of MACE and VTE were detected between those with IL-17i, IL-12/23i, IL-23i and those with TNFi. These findings can serve as a reference to healthcare providers and patients when making clinical decisions, thereby also providing evidence for future pharmacovigilance research.