Impact of IL-17/IL-23 Inhibitors on Subclinical Atherosclerosis in Patients With Plaque Psoriasis, PsA

Studies have evaluated whether controlling the inflammation in psoriasis by inhibiting interleukins (IL) targeting the IL-23/T helper-17 (Th17) axis could reduce the accompanied atherosclerotic process, but the results are inconsistent and the data are sparse. This is according to a systematic review published in Biomedicines.¹

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The IL-23/Th17 pathway plays a role in the pathogenesis of psoriasis and is believed to be implicated in the development of cardiometabolic comorbidities. This systematic reviewsummarized the impact of treatment with biologics targeting the IL-23/Th17 axis on subclinical atherosclerosis in patients with plaque psoriasis and/or psoriatic arthritis (PsA).

Eight studies met the criteria and were included in the review. No studies that assessed the effect of IL-23 inhibitors were identified. Six studies were observational and 2 were randomized controlled trials that evaluated the effect of anti-IL-17 therapy on varied markers of subclinical atherosclerosis. The markers were assessed through static or dynamic imaging or blood-based, soluble biomarkers that indicate or are indirectly related to early alterations of the blood vessels. While 6 studies showed positive effects of biologic therapy, 2 showed no benefit on subclinical atherosclerosis.

It is undetermined whether “discrepancies on the anti-atherogenic effect are associated with differences in patient-related characteristics, principally with regards to their cardiovascular disease (CVD)-risk profile at the onset of biologic therapy, drug-related characteristics such as pharmacologic properties of each IL-17 inhibitor, or difference in sensitivity between the utilized diagnostic techniques,” wrote Aikaterini Tsiogka, MD, of the University of Athens in Greece, and colleagues.

The investigators cited further research that assessed the effect of biological agents on psoriasis-associated CVD and cardiometabolic comorbidities. A 2021 systematic review and meta-analysis examined the impact of IL-12 and IL-23 antagonist ustekinumab, IL-17A antagonist secukinumab or the tumor necrosis factor (TNF)-a inhibitor adalimumab on imaging and biomarkers of CVD, including lipoproteins, inflammation, obesity and insulin resistance. Ustekinumab reduced aortic vascular inflammation and adalimumab reduced C-reactive protein (CRP) and IL-6, but no other benefits were reported in the patients taking the biologics compared with those on placebo. A 2011 meta-analysis reported a potential risk of severe cardiovascular events during ustekinumab initiation, a finding that was supported by a 2020 case-control study.

The latest EuroGuiderm guideline on the treatment of psoriasis vulgaris, including patients with concomitant PsA, recommends that appropriate investigations and treatment should be initiated in patients with established CVD. The guideline also suggested the use of methotrexate, TNF-a inhibitors, ustekinumab and IL-17 inhibitors and avoidance of cyclosporine or acitretin in patients with psoriasis and ischemic heart disease.²

“Future research could include the identification of clinical markers in patients with psoriasis and/or PsA that could predict an optimal anti-atherogenic effect of systemic treatment of psoriasis with biologics,” investigators said. “Future, well-controlled studies could elucidate if different biologic agents may exhibit a more pronounced anti-atherogenic effect and target CVD inflammation more effectively, an association which is yet particularly to be studied in patients receiving IL-23 inhibitors, considering the sparsity of such data in the medical literature.”

References

1. ^{Tsiogka A, Gregoriou S, Stratigos A, et al. The Impact of Treatment with IL-17/IL-23 Inhibitors on Subclinical Atherosclerosis in Patients with Plaque Psoriasis and/or Psoriatic Arthritis: A Systematic Review. Biomedicines. 2023;11(2):318. Published 2023 Jan 23. doi:10.3390/biomedicines11020318}
2. ^{Nast A, Smith C, Spuls PI, et al. EuroGuiDerm Guideline on the systemic treatment of Psoriasis vulgaris - Part 2: specific clinical and comorbid situations. J Eur Acad Dermatol Venereol. 2021;35(2):281-317. doi:10.1111/jdv.16926}