IL-17 Signaling Bridges Psoriasis and Cardiometabolic Risk, Review Finds

Psoriasis rarely stays confined to the skin. Between one-fifth and one-half of patients also carry metabolic syndrome, a risk up to 3 times higher than in the general population, and the interleukin-17 (IL-17) signaling axis appears to be the molecular thread tying the 2 together, according to a review published in the Journal of Dermatological Treatment.¹

Metabolic Syndrome Compounds the Psoriatic Burden

Metabolic syndrome describes the co-occurrence of at least 3 of 5 features—abdominal obesity, elevated triglycerides, low high-density lipoprotein (HDL) cholesterol, hypertension, and insulin resistance—and its prevalence among patients with psoriasis ranges from 20% to 50%.² That burden tracks with cardiovascular morbidity and mortality, and clinicians increasingly treat it as inseparable from the skin disease itself.

The review’s authors point to the “psoriatic march” as the mechanistic explanation: cytokines elevated in severe psoriasis, including IL-17A/F, IL-1β, IL-6, tumor necrosis factor α (TNF-α), and adipokines, act on the liver, adipose tissue, endothelium, and pancreatic β-cells to promote insulin resistance, dyslipidemia, hypertension, and accelerated atherosclerosis.¹ IL-17A and IL-17F drive endothelial dysfunction, oxidative stress, adipose-tissue inflammation, and hepatic fibrogenesis, positioning the cytokine family as a regulator at the interface of immunity and metabolism.

A Narrative Synthesis of 2 Decades of IL-17 Trial Data

The authors searched PubMed/MEDLINE for English-language publications through January 2026, combining terms for psoriasis, the IL-17 pathway, and metabolic disorders with names of specific inhibitors, including secukinumab, ixekizumab, brodalumab, and bimekizumab. Eligible sources spanned trials, mechanistic studies, cohorts, and meta-analyses, plus manually screened reference lists.

That search built on an established efficacy record: IL-17 inhibitors produce complete skin clearance, or a Psoriasis Area and Severity Index score of 100 (PASI100), in roughly a quarter to two-thirds of patients in pivotal trials. The review’s real question was whether blocking the same pathway also touches the cardiometabolic disease that so often accompanies psoriasis.

Cardiovascular Signals Favor IL-17 Blockade, Within Limits

Pooled safety data offer reassurance. Across 10 phase 2/3 secukinumab trials totaling 2725 patient-years, adjudicated major adverse cardiovascular event (MACE) rates were 0.42 (300 mg) and 0.35 (150 mg) per 100 patient-years, comparable with 0.34 for etanercept. Ixekizumab’s long-term pooled rate, about 0.5 per 100 patient-years, tracked similarly, and a network meta-analysis linked bimekizumab to fewer overall cardiovascular events than placebo.

Mechanistic data reinforce that signal. In the CARIMA trial (NCT02559622), 52 weeks of secukinumab significantly improved flow-mediated dilation, a marker of endothelial function, though not at week 12. A prospective observational study linked IL-17 inhibitors to a 12% reduction in noncalcified coronary plaque burden—more than double the 5% reduction with TNF inhibitors—clinically relevant, the authors noted, because noncalcified plaques are the lesions most tied to MACE.

Lipid, Glucose, and Liver Markers Trend Favorably

Metabolomic profiling supplied some striking findings. A nontargeted analysis of ixekizumab-treated patients found dysregulated lipid metabolites—lysophospholipids, diacylglycerols, acylcarnitines—normalized to levels comparable with healthy controls, even among those with coronary heart disease. Ixekizumab also reduced the monocyte-to-HDL-cholesterol ratio, and a short-term randomized comparison found fasting glucose and insulin significantly lower with IL-17 inhibitors than with cyclosporine at 3 months; the drug class was largely weight-neutral overall.

Hepatic and renal data were similarly reassuring. Metabolic dysfunction-associated steatotic liver disease affects up to 65% of patients with psoriasis, and a systematic review the authors cited found IL-17 inhibitors had neutral effects on liver tests in 6 studies and beneficial effects in 5, with secukinumab showing a safer hepatic profile than methotrexate among patients with metabolic syndrome. A network meta-analysis found no increased risk of renal adverse events.

“Understanding these shared molecular pathways is essential for adopting a holistic therapeutic approach that addresses both cutaneous disease and the systemic burden of psoriatic patients,” the authors wrote.

Surrogate Markers Are Not Yet Hard Outcomes, Authors Caution

The authors flagged the evidence’s limits. No IL-17 inhibitor has yet reduced hard cardiovascular outcomes in a dedicated randomized controlled trial; the favorable findings above rest on surrogate markers—flow-mediated dilation, pulse-wave velocity, coronary plaque composition—from studies often limited by small samples and short follow-up. Some improvements, the authors cautioned, may reflect reduced systemic inflammatory burden from effective psoriasis treatment generally, not an IL-17-specific effect.

Because IL-17 inhibitors do not induce weight loss, cardiovascular risk tied to obesity and preexisting metabolic syndrome often persists despite skin clearance; obesity may also blunt drug efficacy. The authors cited the METABOLyx trial (NCT03440736), pairing secukinumab with a lifestyle intervention. The trial itself completed in 2022, with results now posted to ClinicalTrials.gov that could help answer whether such gains translate into fewer clinical events.

The takeaway for dermatologists, payers, and clinicians who co-manage these patients is not that IL-17 inhibitors should be prescribed for metabolic reasons alone. Rather, the review supports treating psoriasis as a systemic disease from the outset, with cardiometabolic screening as routine and drug selection informed by more than PASI scores.

References

1. Gisondi P, Fratton Z, Vighi da Rosa R, Bellini V, Carugno A. Unveiling the IL-17 axis: an immunometabolic bridge between psoriasis and metabolic syndrome. J Dermatolog Treat. 2026;37(1):2673285. doi:10.1080/09546634.2026.2673285
2. De Brandt E, Hillary T. Comorbid psoriasis and metabolic syndrome: clinical implications and optimal management. Psoriasis (Auckl). 2022;12:113-126. doi:10.2147/PTT.S293107