# Cardiovascular Outcomes Associated With Biologic Therapy in Inflammatory Dermatologic Diseases: A Systematic Review

## TL;DR

This review examines how biologic therapies for skin diseases like psoriasis may affect cardiovascular health, finding that some treatments may reduce cardiovascular risk while others show mixed results.

## Contribution

The study provides a systematic review of cardiovascular outcomes associated with biologic therapies in inflammatory dermatologic diseases.

## Key findings

- TNF-α inhibitors are associated with reduced risk of major adverse cardiovascular events compared to conventional therapies.
- Mechanistic studies show improvements in cardiovascular markers like CRP and arterial stiffness with biologic therapies.
- Newer biologic classes show mixed cardiovascular safety and no consistent reduction in major adverse events.

## Abstract

Chronic systemic inflammation is characteristic of many inflammatory dermatoses, with psoriasis showing the closest association. This inflammation is closely linked to atherosclerosis and adverse cardiovascular events. Given that the same pro-inflammatory cytokines targeted by biologic therapies in skin disease are also central to cardiovascular pathophysiology, these treatments may attenuate vascular inflammation with potential implications for cardiovascular risk. This systematic review provides a qualitative analysis of the evidence on the cardiovascular effects of biologic therapies in dermatological diseases and explores potential underlying mechanisms.

A systematic search of PubMed, Embase, and the Cochrane Library identified studies published between 2005 and 2025. Using the population, intervention, comparator, outcomes, and study (PICOS) design framework, studies of patients with psoriasis, psoriatic arthritis, hidradenitis suppurativa, and atopic dermatitis treated with biologics targeting tumor necrosis factor-α (TNF-α), interleukin (IL)-12/23, IL-17, IL-23, or IL-4/13 were included. Two reviewers independently screened and extracted data. Included study designs were randomized controlled trials (RCTs), post hoc phase III analyses, population-based cohorts, registry studies, and mechanistic imaging or biomarker studies. Outcomes included major adverse cardiovascular events (MACE) and surrogate markers, including C-reactive protein (CRP), lipid indices, arterial stiffness, carotid intima-media thickness, and vascular inflammation assessed by fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography. Due to heterogeneity, findings were synthesized narratively.

Seventy-four studies were included in the qualitative synthesis, comprising RCTs, population-based cohort and registry studies, post-hoc analyses of phase III trials, and mechanistic imaging and biomarker studies. Evidence was most robust for TNF-α inhibitors, with multiple large observational studies and meta-analyses suggesting a reduced risk of MACE compared with conventional systemic or topical therapies, despite reports of worse outcomes with high-dose TNF-α inhibition in patients with pre-existing moderate-to-severe heart failure. Mechanistic studies consistently showed improvements in surrogate cardiovascular markers, including CRP, endothelial function, arterial stiffness, and vascular inflammation. For IL-12/23, IL-17, IL-23, and IL-4/13 inhibitors, available data, predominantly from pooled safety analyses, short-term randomized trials, and mechanistic studies, suggested overall cardiovascular safety but no consistent reduction in MACE. Pharmacovigilance analyses identified a potential safety signal for the IL-23 inhibitor risankizumab, with a disproportionately higher incidence of cerebrovascular events than with other biologic therapies for plaque psoriasis.

Biologic therapies, particularly TNF-α inhibitors, demonstrate potential cardiovascular benefit in inflammatory dermatologic diseases. However, results across classes remain inconsistent, reflecting heterogeneity in study design and limited long-term follow-up, particularly for newer classes. Mechanistic and clinical evidence suggest that systemic inflammation control may underpin cardiovascular improvement, yet this effect is unlikely to be uniform across biologic classes.