Effect of Secukinumab on Traditional Cardiovascular Risk Factors and Inflammatory Biomarkers: Post Hoc Analyses of Pooled Data Across Three Indications

Abstract

Background: Psoriasis, psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) are chronic immune-mediated inflammatory diseases (IMIDs) associated with cardiovascular (CV) disease. High-sensitivity C-reactive protein (hsCRP) and, more recently, the neutrophil-lymphocyte ratio (NLR) are important inflammatory biomarkers predictive of CV disease and CV disease-associated mortality. Here, we report the effect of interleukin (IL)-17A inhibition with secukinumab on CV risk parameters in patients with psoriasis, PsA, and axSpA over 1 year of treatment.

Methods: This was a post hoc analysis of pooled data from phase 3/4 secukinumab studies in psoriasis, PsA, and axSpA. CV-related exclusion criteria included uncontrolled hypertension and congestive heart failure. Traditional risk factors assessed were body mass index (BMI) > 25, high fasting glucose and blood pressure (systolic and diastolic), and high cholesterol (low-density lipoproteins [LDL], total cholesterol/HDL ratio, and triglycerides). Inflammatory CV risk parameters assessed were hsCRP and NLR. Statistical analysis was descriptive. Subgroup analyses were performed in high-risk patients defined as having baseline hsCRP > 4 mg/L (patients with psoriasis) and > 10 mg/L (patients with PsA/axSpA).

Results: In total, 9197 patients from 19 clinical trials (8 in psoriasis, n = 4742; 5 in PsA, n = 2475; 6 in axSpA, n = 1980) were included. All traditional CV risk parameters remained stable in secukinumab-treated patients through 1 year. Secukinumab rapidly reduced both hsCRP and the NLR compared with placebo at week 12 (psoriasis) or week 16 (PsA/axSpA) in the overall population and in high-risk patients (all P < 0.01). This reduction was maintained for at least 1 year of secukinumab therapy in all indications.

Conclusions: Secukinumab led to a rapid and sustained reduction in hsCRP and the NLR in patients with IMIDs with a high systemic inflammatory burden. Traditional CV risk factors remained stable for at least 1 year in patients with psoriasis, PsA, and axSpA. Taken together, secukinumab had a favorable effect on systemic inflammation without impact on traditional CV risk factors.

Trials registration: ClinicalTrials.gov, NCT01365455, NCT01358578, NCT01406938, NCT01555125, NCT01636687, NCT02752776, NCT02074982, NCT02826603, NCT01752634, NCT01989468, NCT02294227, NCT02404350, NCT02745080, NCT01863732, NCT01649375, NCT02008916, NCT02159053, NCT02896127, NCT02696031.

Keywords: Axial spondyloarthritis; C-reactive protein; Cardiovascular; Neutrophil–lymphocyte ratio; Psoriasis; Psoriatic arthritis; Secukinumab; Systemic inflammation.

Fig. 1

Median BMI and total cholesterol/HDL with secukinumab over 52 weeks. BMI body mass index, HDL high-density lipoproteins

Fig. 2

Median LDL cholesterol with secukinumab over 52 weeks. LDL low-density lipoprotein

Fig. 3

Effect of secukinumab on inflammatory CV risk parameters in the overall population and the high-risk subgroup over 52 weeks. Data presented as median. *P < 0.0001, ^†P < 0.001, ^ψP < 0.05. P values for comparison between secukinumab 150 mg or 300 mg versus placebo based on Wilcoxon two-sample test for changes from baseline to week 12 (psoriasis)/week 16 (PsA and axSpA). CV cardiovascular