How Systemic Psoriasis Therapies Influence the Risk of New or Recurrent MACEs

Published in the Journal of the American Academy of Dermatology in July 2025, a retrospective cohort study provides new insights for managing patients with psoriasis or psoriatic arthritis (PsA), particularly those with elevated cardiovascular risk.

Using a comprehensive Korean national dataset of over 183,000 individuals treated between 2008 and 2021, the study assessed how systemic therapies influence the risk of both new and recurrent major adverse cardiovascular events (MACEs).

Now, for some background, the link between psoriasis, PsA, and cardiovascular disease (CVD) is known and attributed to chronic systemic inflammation. While earlier research suggested systemic therapies may reduce cardiovascular risk, data have been limited for patients with a history of prior cardiovascular events.

And so in this study, patients were categorized into three treatment groups based on therapy type:

• Biologics
• Nonbiologic systemic agents
• Phototherapy

The primary outcome was the first occurrence of a MACE—defined as acute myocardial infarction, stroke, cardiac arrest, unstable angina, or heart failure—following treatment initiation. The study distinguished between patients with and without a prior MACE, allowing for risk-stratified analysis.

Among patients who’ve never experienced a MACE, biologic therapy was associated with a significantly lower risk of new-onset cardiovascular events compared to phototherapy (adjusted hazard ratio [HR], 0.454; 95% CI, 0.359–0.574). Both TNF-alpha inhibitors and IL-targeting agents (IL-12/23, IL-17, IL-23) contributed to this effect, with non-TNF biologics showing the lowest hazard ratios.

Biologics were similarly effective in patients with a history of MACEs, showing a significantly reduced risk of recurrent events compared to phototherapy (adjusted HR, 0.343; 95% CI, 0.245–0.479). This was observed in a high-risk subgroup with an incidence rate of 105.2 events per 1000 person-years.

In contrast, nonbiologic systemic therapies, including methotrexate and cyclosporine, did not reduce cardiovascular risk in patients without history of MACEs, but they were associated with a modest reduction in recurrence risk among those who’ve experienced MACEs (adjusted HR, 0.789; 95% CI, 0.658–0.946). This heterogeneity may reflect drug-specific properties. For instance, methotrexate has been linked to improved cardiovascular outcomes while cyclosporine may elevate CVD risk.

Additionally, time-dependent Cox regression was used to account for treatment switching and discontinuation. Although the observational design limits causal inference and lacks data on behavioral risk factors such as smoking and alcohol use, the large, nationally representative sample supports generalizability and helps reduce selection bias.

And so to bring this all together, it’s clear that selecting appropriate therapies for patients with psoriasis or PsA who have a history of CVD has posed a clinical challenge. But this population-based study demonstrates that both TNF-α inhibitors and non–TNF-α biologics, including IL-12/23, IL-17, and IL-23 inhibitors, were linked to a reduced risk of both new-onset and recurrent MACEs.

These findings support the consideration of biologic therapies in patients with moderate-to-severe psoriasis or PsA, including those with high cardiovascular risk or a history of MACEs.

Reference:

Song WJ, Oh S, Yoon HS. Association between biologic and nonbiologic systemic therapy for psoriasis and psoriatic arthritis and the risk of new-onset and recurrent major adverse cardiovascular events: A retrospective cohort study. J Am Acad Dermatol. 2025;93(1):141-149.