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Published on: September 20, 2024
Effect of Secukinumab on Traditional Cardiovascular Risk Factors and Inflammatory Biomarkers: Post Hoc Analyses of
Joseph F Merola1, Iain B McInnes2, Atul A Deodhar3
1Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
Insights
Secukinumab treatment rapidly and sustainably reduced inflammatory biomarkers high-sensitivity C-reactive protein (hsCRP) and neutrophil-lymphocyte ratio (NLR) in patients with immune-mediated inflammatory diseases. Traditional cardiovascular risk factors remained stable over one year.
Area of Science:
- Immunology
- Cardiology
- Rheumatology
Background:
- Psoriasis, psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) are immune-mediated inflammatory diseases (IMIDs) linked to cardiovascular (CV) disease.
- High-sensitivity C-reactive protein (hsCRP) and neutrophil-lymphocyte ratio (NLR) are key inflammatory biomarkers for predicting CV disease and mortality.
Purpose of the Study:
- To evaluate the effect of interleukin (IL)-17A inhibitor secukinumab on CV risk parameters in patients with psoriasis, PsA, and axSpA over one year.
- To assess changes in traditional CV risk factors and inflammatory biomarkers (hsCRP, NLR) during secukinumab treatment.
Main Methods:
- Post hoc analysis of pooled data from 19 phase 3/4 secukinumab studies.
- Assessed traditional CV risk factors (BMI, glucose, blood pressure, lipids) and inflammatory markers (hsCRP, NLR).
- Subgroup analyses included patients defined as high-risk based on baseline hsCRP levels.
Main Results:
- Secukinumab treatment led to rapid and sustained reductions in hsCRP and NLR compared to placebo.
- These reductions were observed in the overall population and high-risk subgroups across all indications (psoriasis, PsA, axSpA).
- Traditional CV risk factors remained stable throughout the one-year treatment period.
Conclusions:
- Secukinumab effectively reduces systemic inflammation, indicated by decreased hsCRP and NLR, in patients with IMIDs.
- The treatment demonstrates a favorable effect on systemic inflammation without negatively impacting traditional CV risk factors.
- Secukinumab offers a potential therapeutic option for managing inflammation in patients with psoriasis, PsA, and axSpA, with stable CV risk profiles.
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.
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