Phenotype-dependent effects of IL-17A inhibitors on lipid profiles in moderate-to-severe plaque psoriasis: a retrospective cohort study

BACKGROUND: Psoriasis is associated with elevated cardiovascular risk, partly mediated through dyslipidemia and the interleukin-23/Th17 inflammatory axis. Interleukin-17A (IL-17A) inhibitors demonstrate superior dermatologic efficacy, but their effects on lipid metabolism remain controversial. Most previous studies analyzed lipid changes at the population level without stratifying by baseline lipid phenotypes. This study aimed to evaluate the phenotype-specific effects of IL-17A inhibitors on lipid profiles and identify risk factors for dyslipidemia in moderate-to-severe plaque psoriasis. METHODS: This retrospective cohort study included 353 patients with moderate-to-severe plaque psoriasis (body surface area [BSA] ≥ 3%) treated with IL-17A inhibitors (secukinumab or ixekizumab) for one year. Patients were stratified into five mutually exclusive lipid phenotypes according to the 2023 Chinese guidelines for lipid management. Multivariable logistic regression identified independent risk factors for dyslipidemia. Lipid changes were assessed using paired tests with Benjamini-Hochberg false discovery rate (FDR) correction. Sensitivity analyses were performed in the BSA ≥ 10% subgroup (n = 274). RESULTS: Dyslipidemia was present in 72.2% of patients, with mixed dyslipidemia (26.1%) and hypertriglyceridemia (21.2%) being predominant. BMI ≥ 28 kg/m² (OR = 3.35, 95% CI 1.79-6.28, P < 0.001) and male sex (OR = 2.37, 95% CI 1.40-4.01, P = 0.001) were independent risk factors. Phenotype-specific effects were observed: mixed dyslipidemia patients showed significant reductions in TC (0.47 mmol/L), TG (0.46 mmol/L), and LDL-C (0.18 mmol/L) (all FDR-adjusted P ≤ 0.010); hypercholesterolemia patients demonstrated reductions in TC (0.49 mmol/L) and LDL-C (0.43 mmol/L) (both FDR-adjusted P < 0.001). Among 110 patients with baseline LDL-C ≥ 3.4 mmol/L, 31.0% achieved LDL-C < 3.4 mmol/L. Hypertriglyceridemia patients showed no significant changes after FDR adjustment. Isolated low HDL-C patients exhibited modest increases in HDL-C and LDL-C. Normal lipid patients experienced mild increases in TG and LDL-C within normal ranges. Psoriasis Area and Severity Index (PASI) improvement showed no correlation with lipid changes (all FDR-adjusted P > 0.05). Sensitivity analyses confirmed the robustness of all primary findings. CONCLUSIONS: IL-17A inhibitors exert heterogeneous, phenotype-dependent effects on lipid metabolism. Patients with elevated baseline cholesterol may derive dual dermatologic and cardiometabolic benefits, while those with normal lipids require monitoring for modest unfavorable changes. These findings support phenotype-guided treatment selection and individualized lipid monitoring strategies.