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. Supplementary Information The online version contains supplementary material available at 10.1007/s40744-022-00434-z.

Clinical Efficacy and Safety of Psoriasis Treatments in Patients with Concomitant Metabolic Syndrome: A Narrative Review

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Sequential administration of paricalcitol followed by IL-17 blockade for progressive refractory IgA nephropathy patients

“…The role of adaptive immunity (Th1 and Th17 cells) and IL-17 in the pathogenesis of hypertension has been confirmed by its actions on the proximal and distal tubules, in the thick ascending limb, and the epithelial sodium channel in the collecting duct 39 . Notably, the sole use of SCK did not show benefits in blood pressure in patients with psoriasis, psoriatic arthritis, and axial spondyloarthritis 40 . Further investigation is needed to determine whether the decrease in hypotensive drugs in our patients results from the effect of IL-17A blockade on the arteries, renal environment, or both.…”

Cross-sectional analysis of cardiovascular disease and risk factors in patients with spondyloarthritis: a real-life evidence from biostar nationwide registry

“…TNF inhibitors were associated with a reduced risk of CVD according to the retrospective follow-up analysis of 5046 SpA patients [ 5 ]. Secukinumab and ixekizumab were the selective IL-17A inhibitors that improved the degree of systemic inflammation without negatively impacting traditional CV risk factors [ 5 , 46 , 47 ]. There were questionable relationships between the targeted synthetic DMARDs and MACE risk in SpA patients [ 45 , 48 – 50 ].…”