Effect of Secukinumab on Traditional Cardiovascular Risk Factors and Inflammatory Biomarkers: Post Hoc Analyses of Pooled Data Across Three Indications.
Axial spondyloarthritis
C-reactive protein
Cardiovascular
Neutrophil–lymphocyte ratio
Psoriasis
Psoriatic arthritis
Secukinumab
Systemic inflammation
Journal
Rheumatology and therapy
ISSN: 2198-6576
Titre abrégé: Rheumatol Ther
Pays: England
ID NLM: 101674543
Informations de publication
Date de publication:
Jun 2022
Jun 2022
Historique:
received:
10
12
2021
accepted:
14
02
2022
pubmed:
20
3
2022
medline:
20
3
2022
entrez:
19
3
2022
Statut:
ppublish
Résumé
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. 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). 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. 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. ClinicalTrials.gov, NCT01365455, NCT01358578, NCT01406938, NCT01555125, NCT01636687, NCT02752776, NCT02074982, NCT02826603, NCT01752634, NCT01989468, NCT02294227, NCT02404350, NCT02745080, NCT01863732, NCT01649375, NCT02008916, NCT02159053, NCT02896127, NCT02696031.
Sections du résumé
BACKGROUND
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
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
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
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
BACKGROUND
ClinicalTrials.gov, NCT01365455, NCT01358578, NCT01406938, NCT01555125, NCT01636687, NCT02752776, NCT02074982, NCT02826603, NCT01752634, NCT01989468, NCT02294227, NCT02404350, NCT02745080, NCT01863732, NCT01649375, NCT02008916, NCT02159053, NCT02896127, NCT02696031.
Identifiants
pubmed: 35305260
doi: 10.1007/s40744-022-00434-z
pii: 10.1007/s40744-022-00434-z
pmc: PMC9127026
doi:
Banques de données
ClinicalTrials.gov
['NCT01555125', 'NCT02696031', 'NCT02074982', 'NCT02752776', 'NCT02896127', 'NCT02159053', 'NCT02008916', 'NCT01406938', 'NCT01365455', 'NCT01636687', 'NCT01358578']
Types de publication
Journal Article
Langues
eng
Pagination
935-955Informations de copyright
© 2022. The Author(s).
Références
Arch Dermatol. 2011 Sep;147(9):1031-9
pubmed: 21576552
Autoimmun Rev. 2020 Jan;19(1):102429
pubmed: 31734402
J Dermatol. 2016 Mar;43(3):305-10
pubmed: 26381893
Clin Exp Med. 2019 Feb;19(1):37-45
pubmed: 30478648
Curr Vasc Pharmacol. 2020;18(5):488-506
pubmed: 32056527
JAMA Cardiol. 2018 Jun 1;3(6):455-462
pubmed: 29801037
J Invest Dermatol. 2020 Sep;140(9):1784-1793.e2
pubmed: 32088207
J Invest Dermatol. 2019 May;139(5):1054-1062
pubmed: 30508547
Arthritis Rheum. 2008 Sep;58(9):2612-21
pubmed: 18759273
Ther Adv Musculoskelet Dis. 2021 Jun 30;13:1759720X211027712
pubmed: 34262622
Arthritis Rheum. 2006 Dec;54(12):3790-8
pubmed: 17136752
BMC Res Notes. 2017 Jan 3;10(1):12
pubmed: 28057051
Ann Rheum Dis. 2016 Apr;76(4):654-660
pubmed: 28073800
Biomed Res Int. 2018 Nov 11;2018:2703518
pubmed: 30534554
Curr Med Res Opin. 2008 Feb;24(2):469-80
pubmed: 18179735
J Drugs Dermatol. 2013 Aug;12(8):899-903
pubmed: 23986163
J Eur Acad Dermatol Venereol. 2020 Mar;34(3):533-541
pubmed: 31599476
Rheumatology (Oxford). 2007 Jul;46(7):1122-5
pubmed: 17470434
Front Immunol. 2020 Jan 15;10:3096
pubmed: 32010143
Cardiovasc Res. 2019 Mar 15;115(4):721-728
pubmed: 30721933
Eur Heart J. 2021 Mar 1;42(9):896-903
pubmed: 33417682
Arthritis Rheum. 2012 Jan;64(1):42-52
pubmed: 21898355
Ther Adv Musculoskelet Dis. 2020 Dec 30;12:1759720X20982837
pubmed: 33447266
JAMA Cardiol. 2019 Sep 1;4(9):885-891
pubmed: 31365032
Dermatol Ther. 2020 Jul;33(4):e13628
pubmed: 32431027
Int J Mol Sci. 2017 Dec 25;19(1):
pubmed: 29295598
Rheumatology (Oxford). 2020 Oct 1;59(Suppl4):iv47-iv57
pubmed: 33053193
Trends Cardiovasc Med. 2020 Nov;30(8):472-478
pubmed: 31837960
Front Immunol. 2018 Jun 01;9:1234
pubmed: 29910818
Joint Bone Spine. 2014 Jan;81(1):57-63
pubmed: 23731637
Int Immunopharmacol. 2018 Apr;57:43-46
pubmed: 29471252
Arthritis Rheum. 2007 Sep;56(9):2905-12
pubmed: 17763428
Arthritis Res Ther. 2008;10(2):R30
pubmed: 18325087
Circ Cardiovasc Imaging. 2020 Sep;13(9):e011199
pubmed: 32927971
Ann Rheum Dis. 2011 Apr;70(4):576-82
pubmed: 21109516
N Engl J Med. 2017 Sep 21;377(12):1119-1131
pubmed: 28845751
J Am Acad Dermatol. 2018 Aug;79(2):345-352
pubmed: 29477740
Autoimmun Rev. 2011 Oct;10(12):773-8
pubmed: 21684355
J Invest Dermatol. 2020 Jan;140(1):85-93.e2
pubmed: 31326395
Circulation. 2003 Jan 28;107(3):499-511
pubmed: 12551878
J Cardiovasc Comput Tomogr. 2021 Jul-Aug;15(4):372-379
pubmed: 33390348
Rheumatol Ther. 2015 Dec;2(2):173-182
pubmed: 27747533
J Eur Acad Dermatol Venereol. 2017 Nov;31(11):e491-e492
pubmed: 28502119
Life (Basel). 2021 Sep 05;11(9):
pubmed: 34575068
Int J Mol Sci. 2020 Mar 01;21(5):
pubmed: 32121574
Arthritis Res Ther. 2019 May 2;21(1):111
pubmed: 31046809
Curr Atheroscler Rep. 2017 Oct 30;19(12):53
pubmed: 29086088
J Am Acad Dermatol. 2017 Jan;76(1):81-90
pubmed: 27894789
J Eur Acad Dermatol Venereol. 2013 Aug;27 Suppl 3:12-29
pubmed: 23845149