Cosentyx and low-density lipoprotein cholesterol

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In this retrospective real-world cohort of patients with moderate-to-severe plaque psoriasis treated with Cosentyx (secukinumab), higher baseline low-density lipoprotein cholesterol (LDL) showed a directionally inverse association.

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Background:
Psoriasis is a systemic inflammatory disease frequently accompanied by cardiometabolic comorbidities. Whether baseline lipid status influences clinical response to interleukin-17A blockade remains insufficiently defined.

Objective:
To evaluate the association between baseline low-density lipoprotein cholesterol (LDL) and week-16 clinical response to secukinumab in patients with moderate-to-severe plaque psoriasis and to describe outcomes under 150-mg and 300-mg dosing regimens in real-world practice.

Methods:
We performed a single-center retrospective cohort study including 325 patients with moderate-to-severe plaque psoriasis who received secukinumab for at least 16 weeks.
Patients received either 150 mg or 300 mg secukinumab at weeks 0, 1, 2, 3, and 4 and every 4 weeks thereafter. The primary outcome was achievement of at least 75% improvement in Psoriasis Area and Severity Index (PASI75) at week 16. Propensity score weighting was used to reduce baseline imbalance between dosing groups. The primary association was estimated using multivariable logistic regression with baseline LDL modeled continuously and adjustment for multiple factors. Missing LDL was evaluated using measured-versus-missing comparisons and multiple imputation as a sensitivity analysis.

Results:
After inverse probability weighting, baseline demographic and disease severity variables were generally balanced between dose groups, although residual imbalance in selected laboratory variables remained. Week-16 PASI75 response did not differ significantly between the 150-mg and 300-mg groups after adjustment, while early PASI90 response was more frequent in the 300-mg group and week-16 PASI100 response was more frequent in the 150-mg group. Baseline LDL was inversely associated with PASI75 response at week 16 (ORs per 1 mmol/L increase, 0.696, and 95% CI: 0.497–0.976), and further multiple imputation as a sensitivity analysis confirmed the adjusted OR was 0.718 (95% CI: 0.516–0.999, p = 0.049). Patients with low LDL had a higher PASI75 response rate than those with high LDL (85.2% vs 66.7%). In the 300-mg subgroup, high LDL was associated with lower PASI75 and PASI90 response rates. Secukinumab reduced selected inflammatory and metabolic biomarkers, including CRP, ESR, SCC, glucose, and triglycerides, but LDL and HDL did not show significant improvement over 16 weeks.

Limitations:
This was a retrospective, single-center study with potential residual confounding, missing baseline LDL, a relatively small high-LDL subgroup, retrospectively defined multiplicity families, and the absence of prospective validation.

Conclusions:
Higher baseline LDL was associated with a lower probability of achieving week-16 PASI75 after covariate adjustment. LDL should be considered a hypothesis-generating candidate factor of secukinumab response and may help identify patients who require closer clinical and cardiometabolic monitoring during biologic therapy.

Source: onlinelibrary.wiley.com

*Funding: National Natural Science Foundation of China. Clinical Research Plan of SHDC. Shanghai Municipal Education Commission–Gaofeng Clinical Medicine Grant Support. Innovative Research Team of High-level Local University in Shanghai. Natural Science Foundation of Shanghai Municipality.

Cosentyx (secukinumab)