Comparative assessment of the dynamics of laboratory markers of endothelial dysfunction in patients with psoriasis under the influence of methotrexate and the IL-17A inhibitor netakimab

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Abstract

BACKGROUND: Endothelial dysfunction, a key factor in atherosclerotic vascular damage, increases cardiovascular risk in patients with psoriasis. However, studies on clinically measurable indicators of endothelial dysfunction and their changes during systemic therapy in psoriasis are limited and inconsistent.

AIM: Сomparative assessment of the clinical effect of the IL-17 inhibitor Netakimab and Methotrexate on the values of laboratory markers of endothelial dysfunction in patients with psoriasis in comparison with the dynamics of clinical efficacy indicators over 6 months of therapy.

MATERIALS AND METHODS: The study observed 66 PsA patients initially prescribed Methotrexate (Group 1: 30 patients) or Netakimab (Group 2: 36 patients). Group 1 received Methotrexate 15 mg weekly with Folic acid, while Group 2 received Netakimab 120 mg subcutaneously at weeks 0, 1, 2, then every 4 weeks. Clinical data were analyzed before, 3 months, and 6 months after treatment. Plasma levels of VEGF, endothelin-1 (En-1), and nitric oxide (NO) were measured before treatment and after 3 months.

RESULTS: In psoriasis patients, plasma levels of endothelial dysfunction markers were higher than in the control group: VEGF (19.8 [4.5; 49.4] pg/ml vs. 5.2 [0.5; 9.8] pg/ml, p=0.004), En-1 (286.4 [154; 439] pg/ml vs. 96.5 [32; 188] pg/ml, p=0.002), and NO (4.3 [2.1; 12.5] pg/ml vs. 2.2 [0.2; 5.0] pg/ml, p=0.02). By the third month of therapy, VEGF, En-1, and NO levels decreased, with more significant reductions in Group 2: VEGF decreased by 10.2 [8.4; 13.7] vs. 7.0 [5.6; 11.7] (p=0.043) and En-1 by 184.6 [167; 202] vs. 112.7 [97; 136] (p=0.008) in Group 1. Group 2 also showed a more pronounced decrease in PASI and NAPSI scores at 3 and 6 months.

CONCLUSION: The work demonstrated the ability of the IL-17 inhibitor netakimab to reduce initially elevated values of laboratory markers of endothelial dysfunction.

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About the authors

Olga A. Pritulo

V.I. Vernadsky Crimean Federal University

Email: 55550256@mail.ru
ORCID iD: 0000-0001-6515-1924
SPIN-code: 2988-8463

MD, Dr. Sci. (Medicine), Professor

Russian Federation, 4 Academy Vernadsky ave, Simferopol, Crimean Republic, 295007

Alexey A. Petrov

V.I. Vernadsky Crimean Federal University

Author for correspondence.
Email: ya.alexey2312@yandex.ru
ORCID iD: 0000-0003-4533-2415
SPIN-code: 6070-2810

MD, Cand. Sci. (Medicine)

Russian Federation, 4 Academy Vernadsky ave, Simferopol, Crimean Republic, 295007

Andriy V Petrov

V.I. Vernadsky Crimean Federal University

Email: petroff14@yandex.ru
ORCID iD: 0000-0002-6398-2545
SPIN-code: 3558-8218

MD, Dr. Sci. (Medicine), Professor

Russian Federation, 4 Academy Vernadsky ave, Simferopol, Crimean Republic, 295007

Marwan Y.N. Maraqa

V.I. Vernadsky Crimean Federal University

Email: marakakh73@mail.ru
ORCID iD: 0000-0002-5579-4413
SPIN-code: 5558-4308

MD, Cand. Sci. (Medicine), Assistant Professor

Russian Federation, 4 Academy Vernadsky ave, Simferopol, Crimean Republic, 295007

References

  1. Lockshin B, Balagula Y, Merola JF. Interleukin 17, inflammation, and cardiovascular risk in patients with psoriasis. J Am Acad Dermatol. 2018;79:345–352. doi: 10.1016/j.jaad.2018.02.040
  2. Kuzmina OA, Mironova OY, Lepekhova AA, et al. Effect of psoriasis on cardiovascular risk. Russ J Skin Venereal Dis. 2023;26(5):465–475. doi: 10.17816/dv492288 EDN: GKJYVY
  3. Mehta NN, Yu Y, Pinnelas R, et al. Attributable risk estimate of severe psoriasis on major cardiovascular events. Am J Med. 2011;124:775. doi: 10.1016/j.amjmed.2011.03.028
  4. Kaiser H, Abdulla J, Henningsen KM, et al. Coronary artery disease assessed by computed tomography in patients with psoriasis: A systematic review and meta-analysis. Dermatology. 2019;235(6):478–487. doi: 10.1159/000502138
  5. Raaby L, Ahlehoff O, de Thurah A. Psoriasis and cardiovascular events: Updating the evidence. Arch Dermatol Res. 2017;309(3):225–228. doi: 10.1007/s00403-016-1712-1 EDN: VULKNO
  6. Eder L, Chandran V, Gladman DD. The Framingham risk score underestimates the extent of subclinical atherosclerosis in patients with psoriatic disease. Ann Rheum Dis. 2014;73:1990–1996. doi: 10.1136/annrheumdis-2013-203433
  7. Korsakova YL, Korotayeva TV, Loginova EY, et al. The prevalence of comorbid and concomitant diseases in psoriatic arthritis patients, data from Russian register. Rheumatol Sci Pract. 2021;59(3):275–281. doi: 10.47360/1995-4484-2021-275-281 EDN: QDGWHR
  8. Anyfanti P, Margouta A, Goulas K, et al. Endothelial dysfunction in psoriasis: An updated review. Front Med (Lausanne). 2022;9:864185. doi: 10.3389/fmed.2022.864185 EDN: BQVYZL
  9. Korsakova YL, Korotayeva TV, Loginova EY, et al. The relationship between obesity, cardiometabolic disorders and disease activity in psoriatic arthritis patients: Data from the Russian register. Ther Arch. 2021;93(5):573–580. doi: 10.26442/00403660.2021.05.200789 EDN: UAVISV
  10. Kochergin NG, Brezhneva AA, Yatskova OS, et al. Angiogenesis in psoriasis as a therapeutic target (literature review). Russ J Skin Venereal Dis. 2024;27(3):348–359. doi: 10.17816/dv627134 EDN: LMZSKQ
  11. Fang N, Jiang M, Fan Y. Association between psoriasis and subclinical atherosclerosis. Medicine. 2016;5(20):e3576. doi: 10.1097/MD.0000000000003576
  12. Nakahara T, Kido-Nakahara M, Ulzii D, et al. The pruritogenic mediator endothelin-1 shifts the dendritic cell-T-cell response toward Th17/Th1 polarization. Allergy. 2018;73(2):511–515. doi: 10.1111/all.13322 EDN: YDCSZF
  13. Alba BK, Greaney JL, Ferguson SB, et al. Endothelial function is impaired in the cutaneous microcirculation of adults with psoriasis through reductions in nitric oxide-dependent vasodilation. Am J Physiol Heart Circ Physiol. 2018;314(2):343–349. doi: 10.1152/ajpheart.00446.2017
  14. Lacarrubba F, Pellacani G, Gurgone S, et al. Advances in non-invasive techniques as aids to the diagnosis and monitoring of therapeutic response in plaque psoriasis: A review. Int J Dermatol. 2015;54(6):626–634. doi: 10.1111/ijd.12870
  15. Sankar L, Arumugam D, Boj S, et al. Expression of angiogenic factors in psoriasis vulgaris. J Clin Diagnostic Res. 2017;11(3):23–27. doi: 10.7860/JCDR/2017/23039.9525
  16. Simonetti O, Lucarini G, Goteri G, et al. VEGF is likely a key factor in the link between inflammation and angiogenesis in psoriasis: results of an immunohistochemical study. Int J Immunopathol Pharmacol. 2006;19(4):751–760. doi: 10.1177/039463200601900405
  17. Rashed H, El-Bary EA. Immunohistochemical evaluation of VEGF, surviving, bcl-2 protein and iNOS in the pathogenesis of psoriasis. Egypt J Pathology. 2012;32(1):91–98. doi: 10.1097/01.xej.0000417556.36570.93
  18. Ray A, Maharana KC, Meenakshi S, et al. Endothelial dysfunction and its relation in different disorders: Recent update. Health Sci Rev. 2023;7:100084 doi: 10.1016/j.hsr.2023.100084 EDN: ZPTRTL
  19. Knowles L, Nadeem N, Chowienczyk PJ. Do anti-tumour necrosis factor-α biologics affect subclinical measures of atherosclerosis and arteriosclerosis? A systematic review. Br J Clin Pharmacol. 2020;86(5):837–851. doi: 10.1111/bcp.14215 EDN: JNAFHA
  20. Eder L, Joshi AA, Dey AK, et al. Association of tumor necrosis factor inhibitor treatment with reduced indices of subclinical atherosclerosis in patients with psoriatic disease. Arthritis Rheumatol. 2018;70(3):408–416. doi: 10.1002/art.40366
  21. Von Stebut E, Reich K, Thaçi D, et al. Impact of secukinumab on endothelial dysfunction and other cardiovascular disease parameters in psoriasis patients over 52 weeks. J Invest Dermatol. 2019;139(5):1054–1062. doi: 10.1016/j.jid.2018.10.042 EDN: XHABFF
  22. González-Cantero A, Ortega-Quijano D, Álvarez-Díaz N, et al. Impact of biological agents on imaging and biomarkers of cardiovascular disease in patients with psoriasis: A systematic review and meta-analysis of randomized placebo-controlled trials. J Invest Dermatol. 2021;141(10):2402–2411. doi: 10.1016/j.jid.2021.03.024 EDN: LCJHFH
  23. Hayek SS, Neuman R, Kavtaradze N, et al. Tumor necrosis factor-alpha antagonism with etanercept improves endothelial progenitor cell counts in patients with psoriasis: Etanercept, vascular function and endothelial progenitor cells in psoriasis. Int J Cardiol. 2015;182(1):387–389. doi: 10.1016/j.ijcard.2014.12.093
  24. Ho JC, Lee CH, Lin SH. No significant reduction of circulating endothelial-derived and platelet-derived microparticles in patients with psoriasis successfully treated with anti-IL12/23. Biomed Res Int. 2016;2016:3242143. doi: 10.1155/2016/3242143
  25. Lebwohl MG, Leonardi CL, Mehta NN, et al. Tildrakizumab efficacy, drug survival, and safety are comparable in patients with psoriasis with and without metabolic syndrome: long-term results from 2 phase 3 randomized controlled studies (RESURFACE 1 and RESURFACE 2). J Am Acad Dermatol. 2021;84(2):398–407. doi: 10.1016/j.jaad.2020.09.047
  26. Elnabawi YA, Dey AK, Goyal A, et al. Coronary artery plaque characteristics and treatment with biologic therapy in severe psoriasis: Results from a prospective observational study. Cardiovasc Res. 2019;15;115(4):721–728. doi: 10.1093/cvr/cvz009 EDN: MVYDAH

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