Impact of Interleukin-17 Inhibitor Therapy on Arterial Intima-media Thickness among Severe Psoriatic Patients

Piros, Éva Anna; Szabó, Ákos; Rencz, Fanni; Brodszky, Valentin; Szalai, Klára; Galajda, Noémi; Szilveszter, Bálint; Dósa, Edit; Merkely, Béla; Holló, Péter

doi:10.3390/life11090919

Cited by 13 publications

(9 citation statements)

References 36 publications

(66 reference statements)

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“…Furthermore, in a randomized study in patients with psoriasis, impaired endothelial function at baseline, as measured by flow-mediated dilation, was modestly restored after 52 weeks of secukinumab treatment [ 44 ]. In another study, anti-IL-17 therapy showed ameliorations in arterial intima-media thickness after 6 months of treatment in patients with severe psoriasis, suggesting a potential beneficial effect of anti-IL-17 therapy on cardiovascular complications of systemic inflammation [ 45 ]. Secukinumab decreased hsCRP levels over 52 weeks in patients with psoriasis [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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“… Marovt et al [ 38 ] 2020 Ultrasonography and PWA PsO 15 None (change from baseline) Biologics [(anti-IL-12/23 and IL-17) secukinumab, ustekinumab and ixekizumab] PWV, augmentation index and IMT Biologics targeting the IL-23/IL-17 axis had no effect on vascular structure (IMT) and PWV after 6 months of treatment. Piros et al [ 39 ] 2021 Ultrasound PsO 31 None (change from baseline) Anti-IL-17 [secukinumab, ( N = 20), ixekizumab ( N = 11)] The carotid, brachial and femoral IMT Anti-IL-17 treatment was associated with reduced carotid, brachial and femoral atherosclerosis (IMT) after 6 months of treatment. Gelfand et al [ 40 ] 2022 FDG-PET/CT PsO 70 None (change from baseline) Apremilast Vascular inflammation (TBR) in entire aorta Apremilast had no effect on aortic vascular inflammation after 16 and 52 weeks of treatment.…”

Section: Methodsmentioning

confidence: 99%

Does Systemic Anti-Psoriatic Treatment Impact the Risk of Cardiovascular Disease? A Review Over Cardiovascular Imaging Studies

Kaiser,

Näslund-Koch,

Kvist-Hansen

et al. 2024

Dermatol Ther (Heidelb)

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Psoriasis is an immune-mediated inflammatory disease associated with an increased risk of cardiovascular disease (CVD). The risk of CVD increases with the severity of psoriasis, and exposure to systemic inflammation may partly explain the increased risk of CVD in these patients. This raises the question of whether anti-psoriatic treatment, in addition to treating the skin lesions, also lowers the risk of developing CVD. Different types of studies have examined the impact of systemic anti-psoriatic treatments on the risk of CVD in patients with psoriasis and epidemiological observational studies with, e.g., myocardial infarction and stroke as outcomes, and clinical studies investigating circulating inflammatory biomarkers in the blood indicate that anti-psoriatic therapy has a protective effect; however, no randomized controlled trial (RCT) has examined the impact of systemic anti-psoriatic treatment on future hard cardiovascular endpoints. This narrative review provides an overview of the clinical cardiovascular imaging studies examining the effect of systemic anti-psoriatic treatment on the risk of subclinical CVD in patients with psoriasis. We found a total of 24 clinical imaging studies, where 16 of these were observational cohort studies and eight were RCTs. The observational studies suggest an improvement in the risk of subclinical CVD based on different cardiovascular imaging biomarkers; however, the RCTs showed inconsistent results and mainly included vascular inflammation as the outcome. Future RCTs including other imaging biomarkers as surrogates for subclinical CVD, with longer follow-up and with hard cardiovascular endpoints are warranted to address whether systemic anti-psoriatic treatments reduce the risk of CVD.

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“…RCTs with longer follow-up periods or further well-designed longitudinal studies using data from national and international registers are necessary. For the novel IL-23/Th-17 axis inhibitors, although some studies have shown beneficial effects on the surrogate markers of CV diseases, 107,108 recently published observational studies suggest that IL-12/23, IL-17 and IL-23 inhibitors might be associated with the risk of certain severe CV events. [109][110][111][112] Further comparative studies using real-world data on the effect of different biological therapies of IMIDs on CV risk are needed.…”

Section: Implications For Researchmentioning

confidence: 99%

Reducing cardiovascular risk in immune‐mediated inflammatory diseases: Tumour necrosis factor inhibitors compared to conventional therapies—A systematic review and meta‐analysis

Galajda,

Meznerics,

Mátrai

et al. 2024

Acad Dermatol Venereol

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Immune‐mediated inflammatory disease (IMID) patients including psoriasis, inflammatory arthritides and bowel diseases have a higher risk of developing cardiovascular (CV) diseases compared to the general population. The increased CV risk may be promoted by tumour necrosis factor (TNF)‐α‐mediated immunological processes, which are present both in the pathomechanism of IMIDs and atherosclerosis. Our objective was to comprehensively investigate the effect of TNF inhibitors (TNFi) on CV risk compared with conventional therapies in IMIDs. The systematic literature search was conducted in three databases (MEDLINE, EMBASE, Cochrane Library) on 14 November 2022. Randomized controlled trials, cohort and case–control studies were eligible for inclusion. Outcomes consisted of the incidence of CV events, with major adverse cardiovascular events (MACE) as a main endpoint. A random‐effects meta‐analysis was performed by pooling fully adjusted multivariate hazard ratios (HR) and incidence rate ratios (IRR) with a 95% confidence interval (CI) comparing TNFis with conventional systemic non‐biologicals (CSNBs). Of a total of 8724 search results, 56 studies were included overall, of which 29 articles were eligible for the meta‐analysis, and 27 were involved in the systematic review. Including all IMIDs, the TNFi group showed a significantly reduced risk of MACE compared with the CSNB group (HR = 0.74, 95% confidence interval (CI) 0.58–0.95, p = 0.025; IRR = 0.77, 95% CI 0.67–0.88, p < 0.001). Subgroup analysis of Pso, PsA patients by pooling IRRs also confirmed the significantly decreased risk of MACE in TNFi‐treated patients compared with CSNB groups (IRR = 0.79, 95% CI 0.64–0.98). The observational nature of most included studies leading to high heterogeneity represents a limitation. Based on the results, TNFis may reduce the risk of CV events compared to CSNBs. Therefore, earlier use of TNFis compared to conventional systemic agents in the therapeutic sequence may benefit CV risk in IMID patients.

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Impact of Interleukin-17 Inhibitor Therapy on Arterial Intima-media Thickness among Severe Psoriatic Patients

Cited by 13 publications

References 36 publications

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

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

Does Systemic Anti-Psoriatic Treatment Impact the Risk of Cardiovascular Disease? A Review Over Cardiovascular Imaging Studies

Reducing cardiovascular risk in immune‐mediated inflammatory diseases: Tumour necrosis factor inhibitors compared to conventional therapies—A systematic review and meta‐analysis

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