Research Institute of Pediatrics and Children’s Health in Petrovsky National Research Centre of Surgery
https://doi.org/10.15690/vsp.v22i5.2641
Abstract
Background. Psoriasis is an independent risk factor for cardiovascular diseases (CVD). One of the markers associated with the CVD course is epicardial fatty tissue (EFT) that is thicker in psoriasis patients. EFT assessment can be used as a useful indicator of CVD in psoriasis patients. The data about the effect of genetically engineered biological therapy (GEBT), used for psoriasis management, on the EFT thickness is limited. Examination of GEBT effects on EFT may improve our understanding of CVD prevention in psoriasis patients.
Objective. The aim of the study is to study the changes in EFT thickness on GEBT.
Methods. A prospective cohort study included 56 children with severe and moderate psoriasis. Patients underwent transthoracic two-dimensional echocardiography (M-mode) with EFT thickness assessment and PASI (Psoriasis Area and Severity Index) scoring before the GEBT initiation. All the parameters were re-evaluated after 16 weeks. All patients were divided into three groups according to the initiated therapy: adalimumab, secukinumab and ustekinumab. When dividing the therapy received into groups, the age of the patients was taken into account: inclusion in the adalimumab group was carried out from 4 years, in the secukinumab and ustekinumab groups — from 6 years. Otherwise, the process of group assignment was random. The study results were processed using descriptive statistics methods: the changes in EFT thickness in individual groups were compared via the Wilcoxon test, and results were considered statistically significant at p 0.05.
Results. Before the start of therapy, in 56 patients the mean of EFT thickness was 2.11 mm, the mean PASI — 18.32. The adalimumab group had the following indicators: the mean EFT thickness before the therapy was 2.1 mm, and it has decreased to 1.77 mm after 16 weeks of therapy. The mean change in EFT thickness was 0.33 mm, and the median — 0.17 mm [CI 0.33 ± 0.25]. The ustekinumab group: the mean EFT thickness before the therapy was 2.13 mm, 16 weeks after — 1.69 mm. The mean change in EFT thickness was 0.44 mm, and the median — 0.38 [CI 0.44 ± 0.13]. The secukinumab group: the mean EFT thickness before the therapy was 2.08 mm, 16 weeks after — 1.82 mm. The mean change in EFT thickness was 0.27 mm, and the median — 0.27 [CI 0.27 ± 0.07]. Evaluation of indicators via Wilcoxon test has shown statistically significant decrease in the EFT after therapy in all groups (p 0.05). 73% of patients achieved PASI 50, and 6% — PASI 75 in the adalimumab group. 21% of patients did not achieve PASI 50. The mean PASI score before therapy was 16.73 points, and after 16 ± 4 weeks — 6.4 points, the mean dynamics was 10.33 points, the median dynamics was 7 points [CI 10.33 ± 4]. All patients achieved PASI 50, 75.3% — PASI 75, 8% — PASI 90, and 16.7% — PASI 100 in the ustekinumab group. The mean PASI score before therapy was 22.17 points, and after 16 weeks — 3.67 points, the mean dynamics was 19.28 points, the median dynamics was 17 points [CI 18.5 ± 3.03]. All patients achieved PASI 50, 47% — PASI 75, and 11% — PASI 90 in the secukinumab group. The median PASI before therapy was 14.29 points, and after 16 ± 4 weeks — 3.71 points, the mean PASI score before therapy was 14.29 points, and after 16 weeks — 3.7 points, the mean dynamics was 10.59 points, the median dynamics was 10 points [CI 10.59 ± 2.27]. Evaluation of indicators via Wilcoxon test has shown statistically significant decrease in the PASI after therapy in all groups (p 0.05). There were no adverse events leading to cessation of therapy during the follow-up period.
Conclusion. All groups have shown decrease in the in EFT thickness and in the PASI score. The most significant dynamics was observed in the ustekinumab group. Research limitations were the small patients sample and the absence of a control group (participants without psoriasis).
About the Authors
Leyla S. Namazova-BaranovaRussian Federation
Moscow
Disclosure of interest:
receiving research grants from pharmaceutical companies Pierre Fabre, Genzyme Europe B.V., Astra Zeneca PLC, Gilead / PRA “Pharmaceutical Research Associates CIS”, Teva Branded Pharmaceutical Products R&D, Inc / “PPD Development (Smolensk)” LLC, “Stallerzhen S.A.” / “Quintiles GMBH” (Austria)
Eduard T. Ambarchyan
Russian Federation
Moscow
Disclosure of interest:
receiving research grants from pharmaceutical companies Eli Lilly, Novartis, AbbVie, Pfizer, Amryt Pharma plc. Receiving fees for scientific counseling from Johnson & Johnson
Vladislav V. Ivanchikov
Russian Federation
Moscow
Disclosure of interest:
Other authors confirmed the absence of a reportable conflict of interests
Anastasia D. Kuzminova
Russian Federation
Moscow
Disclosure of interest:
Other authors confirmed the absence of a reportable conflict of interests
Anna G. Shandra
Russian Federation
Moscow
Disclosure of interest:
Other authors confirmed the absence of a reportable conflict of interests
Elena A. Vishneva
Russian Federation
Moscow
Disclosure of interest:
Other authors confirmed the absence of a reportable conflict of interests
Grigorii V. Revunenkov
Russian Federation
Moscow
Disclosure of interest:
Other authors confirmed the absence of a reportable conflict of interests
Kirill A. Valyalov
Russian Federation
Moscow
Disclosure of interest:
Other authors confirmed the absence of a reportable conflict of interests
References
1. Korman NJ. Management of psoriasis as a systemic disease: what is the evidence? Br J Dermatol. 2020;182(4):840–848. doi: https://doi.org/10.1111/bjd.18245
2. Augustin M, Glaeske G, Radtke MA, et al. Epidemiology and comorbidity of psoriasis in children. Br J Dermat. 2010;162(3): 633–636. doi: 10.1111/j.1365-2133.2009.09593.x
3. Parisi R, Symmons DP, Griffiths CE, Ashcroft DM. Global epidemiology of psoriasis: a systematic review of incidence and prevalence. J Invest Dermatol. 2013;133(2):377–385. doi: https://doi.org/10.1038/jid.2012.339
4. Eichenfield LF, Paller AS, Tom WL, et al. Pediatric psoriasis: Evolving perspectives. Pediatr Dermatol. 2018;35(2):170–181. doi: https://doi.org/10.1111/pde.13382
5. Kubanov АА, Bogdanova EV. Dermatovenereology of Russian Federation in 2020: Working Under a Pandemic. Vestnik Dermatologii i Venerologii. 2021;97(4):8–32. (In Russ). doi: https://doi.org/10.25208/vdv1261
6. Liang Y, Sarkar MK, Tsoi LC, Gudjonsson JE. Psoriasis: A mixed autoimmune and autoinflammatory disease. Curr Opin Immunol. 2017;49:1–8. doi: https://doi.org/10.1016/j.coi.2017.07.007
7. Kamata M, Tada Y. Dendritic Cells and Macrophages in the Pathogenesis of Psoriasis. Front Immunol. 2022;13:941071. doi: https://doi.org/10.3389/fimmu.2022.941071
8. Campanati A, Ganzetti G, Di Sario A, et al The effect of etanercept on hepatic fibrosis risk in patients with non‐alcoholic fatty liver disease, metabolic syndrome, and psoriasis. J Gastroenterol. 2013;48(7):839–846. doi: https://doi.org/10.1007/s00535012-0678-9
9. Nowowiejska J, Baran A, Flisiak I. Aberrations in Lipid Expression and Metabolism in Psoriasis. Int J Mol Sci. 2021;22(12):6561. doi: https://doi.org/10.3390/ijms2212656
10. Piaserico S, Orlando G, Messina F. Psoriasis and Cardiometabolic Diseases: Shared Genetic and Molecular Pathways. Int J Mol Sci. 2022;23(16):9063. doi: https://doi.org/10.3390/ijms2316906
11. Zhang L, Wang Y, Qiu L, Wu J. Psoriasis and cardiovascular disease risk in European and East Asian populations: evidence from meta-analysis and Mendelian randomization analysis. BMC Med. 2022;20(1):421. doi: https://doi.org/10.1186/s12916-022-02617-5
12. Barros G, Duran P, Vera I, Bermúdez V. Exploring the Links between Obesity and Psoriasis: A Comprehensive Review. Int J Mol Sci. 2022;23(14):7499. doi: https://doi.org/10.3390/ijms23147499
13. Pannu S, Rosmarin D. Psoriasis in Patients with Metabolic Syndrome or Type 2 Diabetes Mellitus: Treatment Challenges. Am J Clin Dermatol. 2021;22(3):293–300. doi: https://doi.org/10.1007/s40257-021-00590-y
14. Gerdes S, Mrowietz U, Boehncke WH. Comorbidity in psoriasis. Hautarzt. 2016;67(6):438–444. doi: https://doi.org/10.1007/s00105-016-3805-3
15. Ludwig RJ, Herzog C, Rostock A, et al. Psoriasis: A possible risk factor for development of coronary artery calcification. Br J Dermatol. 2007;156(2):271–276. doi: https://doi.org/10.1111/j.1365-2133.2006.07562.x
16. Rendon A, Schäkel K. Psoriasis Pathogenesis and Treatment. Int J Mol Sci. 2019;20(6):1475. doi: https://doi.org/10.3390/ijms2006147
17. Armstrong EJ, Harskamp CT, Armstrong AW. Psoriasis and major adverse cardiovascular events: A systematic review and meta-analysis of observational studies. J Am Heart Assoc. 2013; 2(2):e000062. doi: https://doi.org/10.1161/JAHA.113.000062
18. Puig L, Costanzo A, Muñoz-Elías EJ, et al. The biological basis of disease recurrence in psoriasis: a historical perspective and current models. Br J Dermatol. 2022;186(5):773–781. doi: https://doi.org/10.1111/bjd.20963
19. Mudigonda P, Mudigonda T, Feneran AN, et al. Interleukin-23 and interleukin-17: importance in pathogenesis and therapy of psoriasis. Dermatol Online J. 2012;18(10):1.
20. Jensen P, Skov L. Psoriasis and Obesity. Dermatology. 2016;232(6):633–639. doi: https://doi.org/10.1159/000455840
21. Ambarchyan T, Namazova-Baranova LS, Murashkin NN, et al. Leptin and Epicardial Fat: New Markers of Psoriasis in Children? Prospective Cross-Sectional Study. Pediatricheskaya farmakologiya — Pediatric pharmacology. 2022;19(3):242–249. (In Russ). doi: https://doi.org/10.15690/pf.v19i3.2481
22. Bryld LE, Sorensen TI, Andersen KK, et al. High body mass index in adolescent girls precedes psoriasis hospitalization. Acta Derm Venereol. 2010;90(5):488–493. doi: https://doi.org/10.2340/00015555-0931
23. Kittler NW, Cordoro KM. Pediatric Psoriasis Comorbidities. Skin Therapy Lett. 2020;25(5):1–6.
24. Ambarchian E, Ivanchikov V, Kuzminova A, et al. Comparison of epicardial adipose tissue thickness of paediatric patients with concomitant moderate to severe psoriasis and control group. Poster Presentations. Pediatr Dermatol. 2023;40(S2):10–89. doi: https://doi.org/10.1111/pde.15301
25. Wang X, Guo Z, Zhu Z, et al. Epicardial fat tissue in patients with psoriasis:a systematic review and meta-analysis. Lipids Health Dis. 2016;15:103. doi: https://doi.org/10.1186/s12944-016-0271-y
26. Iacobellis G. Epicardial and pericardial fat: Close, but very different. Obesity (Silver Spring). 2009;17(7):625. doi: https://doi.org/10.1038/oby.2008.575
27. Iacobellis G, Bianco AC. Epicardial adipose tissue: Emerging physiological, pathophysiological and clinical features. Trends Endocrinol Metab. 2011;22(11):450–457. doi: https://doi.org/10.1016/j.tem.2011.07.003
28. Gorter PM, de Vos AM, van der Graaf Y, et al. Relation of epicardial and pericoronary fat to coronary atherosclerosis and coronary artery calcium in patients undergoing coronary angiography. Am J Cardiol. 2008;102(4):380–385. doi: https://doi.org/10.1016/j.amjcard.2008.04.002
29. Djaberi R, Schuijf JD, van Werkhoven JM, et al. Relation of epicardial adipose tissue to coronary atherosclerosis. Am J Cardiol. 2008;102(12):1602–1607. doi: https://doi.org/10.1016/j.amjcard.2008.08.010
30. de Vos AM, Prokop M, Roos CJ, et al. Peri-coronary epicardial adipose tissue is related to cardiovascular risk factors and coronary artery calcification in post-menopausal women. Eur Heart J. 2008;29(6): 777–783. doi: https://doi.org/10.1093/eurheartj/ehm564
31. Iacobellis G. Epicardial adipose tissue in contemporary cardiology. Nat Rev Cardiol. 2022;19(9):593–606. doi: https://doi.org/10.1038/s41569-022-00679-9
32. Iacobellis G. Local and systemic effects of the multifaceted epicardial adipose tissue depot. Nat Rev Endocrinol. 2015;11(6): 363–371. doi: https://doi.org/10.1038/nrendo.2015.58
33. Iacobellis G, Mohseni M, Bianco SD, Banga PK. Liraglutide causes large and rapid epicardial fat reduction. Obesity (Silver Spring). 2017;25(2):311–316. doi: https://doi.org/10.1002/oby.21718
34. Bouchi R, Terashima M, Sasahara Y, et al. Luseogliflozin reduces epicardial fat accumulation in patients with type 2 diabetes: a pilot study. Cardiovasc Diabetol. 2017;16(1):32. doi: https://doi.org/10.1186/s12933-017-0516-8
35. Neeland IJ, Marso SP, Ayers CR, et al. Effects of liraglutide on visceral and ectopic fat in adults with overweight and obesity at high cardiovascular risk: a randomised, double-blind, placebo-controlled, clinical trial. Lancet Diabetes Endocrinol. 2021;9(9):595–605. doi: https://doi.org/10.1016/S2213-8587(21)00179-0
36. Renzo LD, Saraceno R, Schipani C, et al. Prospective assessment of body weight and body composition changes in patients with psoriasis receiving anti-TNF-α treatment. Dermatol Ther. 2011;24(4):446–451. doi: https://doi.org/10.1111/j.1529-8019.2011.01439.x
37. Gisondi P, Cotena C, Tessari G, Girolomoni G. Anti-tumour necrosis factor-alpha therapy increases body weight in patients with chronic plaque psoriasis: a retrospective cohort study. J Eur Acad Dermatol Venereol. 2008;22(3):341–344. doi: https://doi.org/10.1111/j.1468-3083.2007.02429.x
38. Phan C, Beauchet A, Burztejn AC, et al. Biological treatments for paediatric psoriasis : a retrospective observational study on biological drug survival in daily practice in childhood psoriasis. J Eur Acad Dermatol Venereol. 2019;33(10):1984–1992. doi: https://doi.org/10.1111/jdv.15579
39. Gisondi P, Conti A, Galdo G, et al. Ustekinumab does not increase body mass index in patients with chronic plaque psoriasis: a prospective cohort study. Br J Dermatol. 2013;168(5): 1124–1127. doi: https://doi.org/10.1111/bjd.12235
40. 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: https://doi.org/10.1016/j.jid.2021.03.024
41. Koschitzky M, Navrazhina K, Garshick MS, et al. Ustekinumab reduces serum protein levels associated with cardiovascular risk in psoriasis vulgaris. Exp Dermatol. 2022;31(9):1341–1351. doi: https://doi.org/10.1111/exd.14582
42. Lima-Martínez MM, Campo E, Salazar J, et al. Epicardial fat thickness as cardiovascular risk factor and therapeutic target in patients with rheumatoid arthritis treated with biological and nonbiological therapies. Arthritis. 2014;2014:782850. doi: https://doi.org/10.1155/2014/782850
43. Ivanov RA, Murashkin NN. Biological Therapy Survivability in Children with Psoriasis: Cohort Study. Voprosy sovremennoi pediatrii — Current Pediatrics. 2021;20(5):451–458. (In Russ). doi: https://doi.org/10.15690/vsp.v20i5.2323
44. Landells I, Marano C, Hsu MC, et al. Ustekinumab in adolescent patients age 12 to 17 years with moderate-to-severe plaque psoriasis: results of the randomized phase 3 CADMUS study. J Am Acad Dermatol. 2015;73(4):594–603. doi: https://doi.org/10.1016/j.jaad.2015.07.002
45. Philipp S, Menter A, Nikkels AF, et al. Ustekinumab for the treatment of moderate-to-severe plaque psoriasis in pediatric patients (6 to < 12 years of age): efficacy, safety, pharmacokinetic, and biomarker results from the open-label CADMUS Jr study. Br J Dermatol. 2020;183(4):664–672. doi: https://doi.org/10.1111/bjd.19018
Review
For citations:
Namazova-Baranova L.S., Ambarchyan E.T., Ivanchikov V.V., Kuzminova A.D., Shandra A.G., Vishneva E.A., Revunenkov G.V., Valyalov K.A. Research Institute of Pediatrics and Children’s Health in Petrovsky National Research Centre of Surgery. Current Pediatrics. 2023;22(5):406-414. https://doi.org/10.15690/vsp.v22i5.2641