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Vliv dlouhodobé terapie adalimumabu na biomarkery systémového zánětu u psoriázy


The Influence of Long Term Therapy with Adalimumab on Biomarkers of Systemic Inflammation in Psoriasis

Patients with psoriasis are at increased risk of atherosclerosis, which is characterized by endothelial dysfunction associated with systemic inflammation. It appears that anti-tumor necrosis alpha treatment may reduce this risk. The purpose of this study was to measure serum marker levels associated with systemic inflammation in patients with psoriasis compared to healthy subjects and to further evaluate the change in their levels after 3 months and 2 years of treatment with adalimumab. We investigated four biomarkers: highly sensitive C-reactive protein (hsCRP), oxidized low density lipoproteins (OxLDL), E-selectin and Interleukin 22 (IL-22). These markers were determined in healthy volunteers and in 28 patients with moderate to severe psoriasis before and after 3 and 24 months of adalimumab treatment. Patients with psoriasis had elevated markers levels compared to controls. After 3 months of treatment, E-selectin decreased significantly (p < 0.001), same as IL-22 (p < 0.001). HsCRP also decreased, but statistically insignificantly, OxLDLs were slightly higher than originally. After 24 months, 17 patients were still treated with adalimumab. In these patients, HsCRP (p < 0.05), E-selectin (p < 0.001) and IL-22 (p < 0.001) were significantly reduced. The OxLDL value remained elevated. A steady decrease in E-selectin, hsCRP and IL-22 after 24 months confirms that adalimumab suppresses systemic inflammation. Key words: adalimumab – biomarkers – psoriasis

Keywords:

adalimumab – biomarkers – Psoriasis – systemic inflammation


Autoři: S. Gkalpakiotis 1;  P. Arenberger 1;  S. Tivadar 1;  P. Gkalpakioti 1;  J. Potočková 2;  P. Kraml 2
Působiště autorů: Dermatovenerologická klinika, 3. lékařská fakulta Univerzity Karlovy a Fakultní nemocnice Královské Vinohrady, přednosta prof. MUDr. Petr Arenberger, DrSc, MBA, FCMA 1;  Interní klinika, 3. lékařská fakulta Univerzity Karlovy a Fakultní nemocnice Královské Vinohrady, přednosta prof. MUDr. Ivan Rychlik, CSc., FASN, FERA 2
Vyšlo v časopise: Čes-slov Derm, 96, 2021, No. 4, p. 179-185
Kategorie: Terapie, farmakologie a klinické studie

Souhrn

Pacienti s psoriázou jsou vystaveni zvýšenému riziku aterosklerózy, která je charakterizovaná endotelovou dysfunkcí spojenou se systémovým zánětem. Zdá se, že léčba anti-tumor nekrotizujícím faktorem alfa (anti-TNF-a) může toto riziko snížit. Účelem studie bylo změřit hladiny sérových markerů asociovaných se systémovým zánětem u pacientů s psoriázou v porovnaní se zdravými jedinci a dále zhodnotit změnu jejich hladin po 3 měsících a 2 letech při léčbě anti-TNF alfa adalimumabem. Zkoumali jsme čtyři biomarkery: vysoce senzitivní C-reaktivní protein (hsCRP), oxidovaný lipoprotein s nízkou hustotou (OxLDL), E-selektin a Interleukin 22 (IL-22). Tyto markery byly stanoveny u zdravých dobrovolníků a u 28 pacientů se středně těžkou až těžkou psoriázou před léčbou a po 3 a 24 měsících léčby adalimumabem. Pacienti s psoriázou měli zvýšené hladiny markerů ve srovnání s kontrolní skupinou. Po 3 měsících léčby významně poklesl E-selektin (p < 0,001), stejně tak IL-22 (p < 0,001). HsCRP pokleslo také, ale statisticky nevýznamně, OxLDL byl lehce vyšší než původně. Po 24 měsících bylo 17 pacientů stále léčeno adalimumabem. U těchto pacientů hsCRP (p < 0,05), E-selektin (p < 0,001) a IL-22 (p < 0,001) byly signifikantně snížené. Hodnota OxLDL zůstala zvýšena. Stabilní pokles E-selektinu, hsCRP a IL-22 po 24 měsících potvrzuje, že adalimumab potlačuje systémový zánět.


Zdroje

1. AWAD, S. M., ATTALLAH, D. A., SALAMA, R. H., MAHRAN, A. M., ABU EL-HAMED, E. Serum levels of psoriasin (S100A7) and koebnerisin (S100A15) as potential markers of atherosclerosis in patients with psoriasis. Clin Exp Dermatol., 2018, 43, p. 262– 267.

2. BOEHNCKE, W. H., BOENHCKE, S., TOBIN, A. M., KIRBY, B. The ‚psoriatic march‘: a concept of how severe psoriasis may drive cardiovascular comorbidity. Exp Dermatol., 2011, 20, p. 303–307.

3. BOENHCKE, W.-H. Systemic inflammation and cardiovascular comorbidity in psoriasis patients: causes and consequences. Front Immunol., 2018, 9, p. 579.

4. DAVIDOVICI, B. B., SATTAR, N., PRINZ, J. et al. Psoriasis and systemic inflammatory diseases: potential mechanistic links between skin disease and comorbid conditions. J Invest Dermatol., 2010, 130, p. 1785–1796.

5. GELFAND, J. M., SHIN, D. B., DUFFIN, K. C. et al. A randomized placebo controlled trial of Secukinumab on aortic vascular inflammation in moderate to severe plaque psoriasis (VIP-S). J Invest Dermatol., 2020. [Epub ahead of print]. Dostupné na www: https://doi.org/10.1016/j.jid.2020.01.025.

6. GENRE, F., ARMESTO, S., CORRALES, A. et al. Significant sE-selectin levels reduction after 6 months of anti-TNF therapy in non-diabetic patients with moderate-to-severe psoriasis. J Dermatolog Treat., 2017, 28, p. 726–730.

7. GERDES, S., OSADTSCHY, S., BUHLES, N., BAUERCHT, H., MROWIETZ, U. Cardio- vascular biomarkers in patients with psoriasis. Exp Dermatol., 2014, 23, p. 322–325.

8. GISONDI, P., FOSTINI, A. C., FOSSÁ, I., GIROLOMONI, G., TARGHER, G. Psoriasis and the metabolic syndrome. Clin Dermatol., 2018, 36, p. 21–28.

9. GKALPAKIOTIS, S., ARENBERGEROVA, M., GKALPAKIOTI, P., POTOCKOVA, J., ARENBERGER, P., KRAML, P. Impact of adalimumab treatment on cardiovascular risk biomarkers in psoriasis: results of a pilot study. J Dermatol., 2017, 44, p. 363–369.

10. HOPE, S. A., MEREDITH, I. T. Cellular adhesion molecules and cardiovascular disease. Part II. Their association with conventional and emerging risk factors, acute coronary events and cardiovascular risk prediction. Intern Med J., 2003, 33, p. 450–462.

11. JÓKAI, H., SZAKONYI, J., KONTÁR, O. et al. Impact of effective tumor necrosis factor-alfa inhibitor treatment on arterial intimal-media thickness in psoriasis: results of a pilot study. J Am Acad Dermal., 2013, 69, p. 523–529.

12. JUNG, K. J., KIM, T. G., LEE, J. W. et al. Increased risk of atherosclerotic car-diovascular disease among patients with psoriasis in Korea: a 15-year nationwide population-based cohort study. J Dermatol., 2019, 46(10), p. 859–866.

13. KARADAG, A. S., YAVUZ, B., ERTUGRUL, D. T. et al. Is psoriasis a pre- atherosclerotic disease? Increased insulin resistance and impaired endothelial function in patients with psoriasis. Int J Dermatol., 2010, 49, p. 642–646.

14. KHAMBHATI, J., ENEGELS, M., ALLARD-RATICK, M., SANDESARA, P. B., QUYYUMI, A. A., SPERLING, L. Immunotherapy for the prevention of atherosclerotic cardiovascular disease: promise and possibilities. Atherosclerosis, 2018, 276, p. 1–9.

15. KIM, J. A., MONTAGNANI, M., KOH, K. K., QUON, M. J. Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms. Circulation, 2006, 113, p. 1888–1904.

16. LIU, H., YAO, Y., WANG, Y. et al. Association between high-sensitivity C- reactive protein, lipoprotein-associated phospholipase A2 and carotid atherosclerosis: a cross-sectional study. J Cell Mol Med., 2018, 22, p. 5145–5150.

17. MALIK, I., DANESH, J., WHINCUP, P. et al. Soluble adhesion molecules and prediction of coronary heart disease: a prospective study and meta-analysis. Lancet, 2001, 358, p. 971–976.

18. MARTIN, J. C., WOLK, K., BÉRIOU, G. et al. Limited presence of IL-22 binding protein, a natural IL-22 inhibitor, strengthens psoriatic skin inflammation. J Immunol., 2017, 198, p. 3671–3678.

19. MASZTALEWIC, M., NOWACKI, P., KOTLEGA, D., BAJER- CZAJKOWSKA, A., DRECHSLER, H. Anti-oxLDL antibodies are clinically insignificant for stroke patients. Neurol Res., 2014, 36, p. 86–91.

20. MÄKI-PETÄJÄ, K. M., ELKHAWAD, M., CHERIVAN, J. et al. Anti-tumor necrosis factor-α therapy reduces aortic inflammation and stiffness in patients with rheumatoid arthritis. Circulation, 2012,126, p. 2473– 2480.

21. MÄKI-PETÄJÄ, K. M., ELKHAWAD, M., CHERIVAN, J. et al. Effective continuous systemic therapy of severe plaque-type psoriasis is accompanied by amelioration of biomarkers of cardiovascular risk: results of a prospective longitudinal observational study. J Eur Acad Dermatol Venereol., 2011, 25, p. 1187–1193.

22. MEHTA, N. N., AZFAR, R. S., SHIN, D. B., NEIMANN, A. L., TROXEL, A. B., GELFAND, J. M. Patients with severe psoriasis are at increased risk of cardiovascular mortality: cohort study using the General Practice Research Database. Eur Heart J., 2010, 31, p. 1000– 1006.

23. PATEL, N., NADKARNI, A., CARDWELL, L. A. et al. Psoriasis, depression, and inflammatory overlap: a review. Am J Clin Dermatol., 2017,18, p. 613–662.

24. PINA, T., GENRE, F., LOPEZ-MEJIAS, R. et al. Asymmetric dimethylarginine but not osteoprotegerin correlates with disease severity in patients with moderate-to-severe psoriasis undergoing anti-tumor necrosis factor: a therapy. J Dermatol., 2016, 43, p. 389–394.

25. PIRILLO, A., NORATA, G. D., CATAPANO, A. L. LOX- 1, OxLDL, and atherosclerosis. Mediators Inflamm., 2013, p. 152786.

26. RAABY, L., AHLEHOFF, O., de THURAH, A. Psoriasis and cardiovascular events: updating the evidence. Arch Dermatol Res., 2017, 309, p. 225–228.

27. ROBATI, R. M., PARTOVI-KIA, M., SADAT-AMINI, H., HAGHIGHATKHAH, H. R., YOUNESPOUR, S., TOOSSI, P. Serum osteopontin level and common carotid artery intima-media wall thickness in psoriasis. Int J Dermatol., 2016, 55, e.262–e267.

28. SHI, L., Ji, Q., LIU, L. et al. IL-22 produced by Th22 cells aggravates ath- erosclerosis development in ApoE−/− mice by enhancing DC-induced Th17 cell proliferation. J Cell Mol Med., 2020, 24, p. 3064– 3078.

29. TAKAHASHI, H., TSUJI, H., HASHIMOTO, Y., ISHIDA- -YAMAMOTO, A., IIZUKA, H. Serum cytokines and growth factor levels in Japanese patients with psoriasis. Clin Exp Dermatol., 2010, 35, p. 645–649.

30. TEKIN, N. S., TEKIN, I. O., BARUT, F., SIPAHI, E. Y. Accumulation of oxidized low-density lipoprotein in psoriatic skin and changes of plasma lipid levels in psoriatic patients. Mediators Inflamm., 2007, p. 78454.

Štítky
Dermatológia Detská dermatológia
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