rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2015-553-557rsp-2132Research ArticleОБЗОРREVIEWЭффективность цертолизумаба пэгола в лечении псориатического артритаEFFICACY OF CERTOLIZUMAB PEGOL IN THE TREATMENT OF PSORIATIC ARTHRITISКоротаеваТ. В.KorotaevaT. V.tatianakorotaeva@gmail.comЛогиноваЕ. Ю.LoginovaE. Yu.ФГБНУ Научно-исследовательский институт ревматологии им. В.А. Насоновой, Москва, Россия 115522 Москва, Каширское шоссе, 34АРоссияV.A. Nasonova Research Institute of Rheumatology, Moscow, Russia 34A, Kashirskoe Shosse, Moscow 115522Russian Federation201514102015535553557Copyright © Коротаева Т.В., Логинова Е.Ю., 20152015Коротаева Т.В., Логинова Е.Ю.Korotaeva T.V., Loginova E.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/2132

Выполнен анализ данных литературы о механизмах действия цертолизумаба пэгола (ЦЗП) – нового ингибитора фактора некроза опухоли α (ФНОα) для лечения активного псориатического артрита (ПсА). Описаны уникальная молекулярная структура препарата, механизм действия, показано, что ЦЗП эффективно ингибирует ФНОα, не вызывая клеточный апоптоз, а также обладает низкой иммуногенностью. Рассмотрены результаты клинического исследования ЦЗП – RAPID-PsA. Отмечена быстрая клиническая эффективность лечения ЦЗП в разных дозах в отношении проявлений как артрита, так и псориаза. Приведены данные о том, что терапия ЦЗП препятствует образованию эрозий в суставах, особенно у пациентов с активным заболеванием. Сделан вывод, что ЦЗП – перспективный препарат для лечения активного ПсА, однако необходимо проведение дальнейших фундаментальных и клинических исследований этого класса лекарственных средств, направленных против определенных цитокинов.

The paper analyzes the data available in the literature on the mechanisms of action of certolizumab pegol (CZP), a new tumor necrosis factor-α (TNF-α) inhibitor for the treatment of active psoriatic arthritis (PsA). It describes the unique molecular structure of the drug and its mechanism of action and shows that CZP effectively inhibits TNF-α, without inducing cell apoptosis, and has also low immunogenicity. The results of the RAPID-PsA clinical trial of CZP are discussed. Treatment with CZP at different doses promptly suppresses the manifestations of both arthritis and psoriasis. There is evidence that CZP therapy prevents joint erosion formation in patients with active disease in particular. It is concluded that CZP is a promising drug to treat active PsA; however, it is necessary to conduct further fundamental and clinical studies of this class of drugs against certain cytokines.

псориатический артритгенно-инженерные биологические препаратыцертолизумаба пэгол.psoriatic arthritisbiological agentscertolizumab pegolReferencesKane D, Stafford L, Bresnihan B, FitzGerald O. A prospective, clinical and radiological study of early psoriatic arthritis: an early synovitis clinic experience. Rheumatology (Oxford). 2003;42(12):1460–8. doi: 10.1093/rheumatology/keg384Kane D, Stafford L, Bresnihan B, FitzGerald O. A prospective, clinical and radiological study of early psoriatic arthritis: an early synovitis clinic experience. Rheumatology (Oxford). 2003;42(12):1460–8. doi: 10.1093/rheumatology/keg384Mease PJ. Tumor necrosis factor (TNF) in psoriatic arthritis: pathophysiology and treatment with TNF inhibitors. Ann Rheum Dis. 2002;61:298–304. doi: 10.1136/ard.61.4.298Mease PJ. Tumor necrosis factor (TNF) in psoriatic arthritis: pathophysiology and treatment with TNF inhibitors. Ann Rheum Dis. 2002;61:298–304. doi: 10.1136/ard.61.4.298Laloux L, Voisin MC, Allain J, et al. Immunohistological study of entheses in spondyloarthropathies: comparison in rheumatoid arthritis and osteoarthritis. Ann Rheum Dis. 2001;60(4):316–21. doi: 10.1136/ard.60.4.316Laloux L, Voisin MC, Allain J, et al. Immunohistological study of entheses in spondyloarthropathies: comparison in rheumatoid arthritis and osteoarthritis. Ann Rheum Dis. 2001;60(4):316–21. doi: 10.1136/ard.60.4.316Saad AA, Ashcroft DM, Watson KD, et al, BSRBR. Efficacy and safety of anti-TNF therapies in psoriatic arthritis: an observational study from the British Society for Rheumatology Biologics Register. Rheumatology (Oxford). 2010;49(4):697–705. doi: 10.1093/rheumatology/kep423Saad AA, Ashcroft DM, Watson KD, et al, BSRBR. Efficacy and safety of anti-TNF therapies in psoriatic arthritis: an observational study from the British Society for Rheumatology Biologics Register. Rheumatology (Oxford). 2010;49(4):697–705. doi: 10.1093/rheumatology/kep423Ritchlin CT, Kavanaugh A, Gladman DD, et al. Treatment recommendations for psoriatic arthritis. Ann Rhem Dis. 2009;68(9):1387–94. doi: 10.1136/ard.2008.094946Ritchlin CT, Kavanaugh A, Gladman DD, et al. Treatment recommendations for psoriatic arthritis. Ann Rhem Dis. 2009;68(9):1387–94. doi: 10.1136/ard.2008.094946Ritchlin CT, Haas-Smith SA, Li P, et al. Mechanisms of TNF-α and RANKL-mediated osteoclastogenesis and bone resorption in psoriatic arthritis. J Clin Invest. 2003;111(6):821–31. doi: 10.1172/JCI200316069Ritchlin CT, Haas-Smith SA, Li P, et al. Mechanisms of TNF-α and RANKL-mediated osteoclastogenesis and bone resorption in psoriatic arthritis. J Clin Invest. 2003;111(6):821–31. doi: 10.1172/JCI200316069Palframan R, Airey M, Moore A, et al. Use of biofluorescence imaging to compare the distribution of certolizumab pegol, adalimumab, and infliximab in the inflamed paws of mice with collagen-induced arthritis. J Immun Method. 2009;348(1–2):36–41. doi: 10.1016/j.jim.2009.06.009Palframan R, Airey M, Moore A, et al. Use of biofluorescence imaging to compare the distribution of certolizumab pegol, adalimumab, and infliximab in the inflamed paws of mice with collagen-induced arthritis. J Immun Method. 2009;348(1–2):36–41. doi: 10.1016/j.jim.2009.06.009Dinesen L, Trevis S. Targeting nanomedicines in the treatment of Crohn's disease: focus on certolizumab pegol (CDP870). Inter J Nanomed. 2007;2(1):39–47. doi: 10.2147/nano.2007.2.1.39Dinesen L, Trevis S. Targeting nanomedicines in the treatment of Crohn's disease: focus on certolizumab pegol (CDP870). Inter J Nanomed. 2007;2(1):39–47. doi: 10.2147/nano.2007.2.1.39Choy C, Hazleman B, Smith M, et al. Efficacy of a novel PEGylated humanized anti-TNF fragment (CDP870) in patients with rheumatoid arthritis: a phase II double-blinded, randomized, dose-escalating trial. Rheumatology. 2002;41(10):1133–7. doi: 10.1093/rheumatology/41.10.1133Choy C, Hazleman B, Smith M, et al. Efficacy of a novel PEGylated humanized anti-TNF fragment (CDP870) in patients with rheumatoid arthritis: a phase II double-blinded, randomized, dose-escalating trial. Rheumatology. 2002;41(10):1133–7. doi: 10.1093/rheumatology/41.10.1133Harris JM, Martin NE, Modi M. Pegylation: a novel process for modifying pharmacokinetics. Clin Pharmacokinet. 2001;40(7):539–51. doi: 10.2165/00003088-200140070-00005Harris JM, Martin NE, Modi M. Pegylation: a novel process for modifying pharmacokinetics. Clin Pharmacokinet. 2001;40(7):539–51. doi: 10.2165/00003088-200140070-00005Nesbitt A, Fossati G, Bergin M, et al. Mechanism of action of certolizumab pegol (CDP870): in vitro comparison with other antitumor necrosis factor agents. Inflamm Bowel Dis. 2007;13(11):1323. doi: 10.1002/ibd.20225Nesbitt A, Fossati G, Bergin M, et al. Mechanism of action of certolizumab pegol (CDP870): in vitro comparison with other antitumor necrosis factor agents. Inflamm Bowel Dis. 2007;13(11):1323. doi: 10.1002/ibd.20225Ueda N, Tsukamoto H, Mitoma H, et al. The cytotoxic effects of certolizumab pegol and golimumab mediated by transmembrane tumor necrosis factor α. Ann Rheum Dis. 2012;71 Suppl 3:665. doi: 10.1136/annrheumdis-2012-eular.482Ueda N, Tsukamoto H, Mitoma H, et al. The cytotoxic effects of certolizumab pegol and golimumab mediated by transmembrane tumor necrosis factor α. Ann Rheum Dis. 2012;71 Suppl 3:665. doi: 10.1136/annrheumdis-2012-eular.482Ohshima S, Saeki Y, Mima T, et al. Long-term follow-up of the changes in circulating cytokines, soluble cytokine receptors, and white blood cell subset counts in patients with rheumatoid arthritis (RA) after monoclonal anti-TNF alpha antibody therapy. J Clin Immunol. 1999;19(5):305–13. doi: 10.1023/A:1020543625282Ohshima S, Saeki Y, Mima T, et al. Long-term follow-up of the changes in circulating cytokines, soluble cytokine receptors, and white blood cell subset counts in patients with rheumatoid arthritis (RA) after monoclonal anti-TNF alpha antibody therapy. J Clin Immunol. 1999;19(5):305–13. doi: 10.1023/A:1020543625282Taylor PC. Pharmacology of TNF blockade in rheumatoid arthritis and other chronic inflammatory diseases. Curr Opin Pharmacol. 2010;10(3):308–15. doi: 10.1016/j.coph.2010.01.005Taylor PC. Pharmacology of TNF blockade in rheumatoid arthritis and other chronic inflammatory diseases. Curr Opin Pharmacol. 2010;10(3):308–15. doi: 10.1016/j.coph.2010.01.005Kirchner S, Holler E, Haffner S, et al. Effect of different tumor necrosis factor (TNF) reactive agents on reverse signalling of membrane integrated TNF in monocytes. Cytokine. 2004;28(2):67–74. doi: 10.1016/j.cyto.2004.06.008Kirchner S, Holler E, Haffner S, et al. Effect of different tumor necrosis factor (TNF) reactive agents on reverse signalling of membrane integrated TNF in monocytes. Cytokine. 2004;28(2):67–74. doi: 10.1016/j.cyto.2004.06.008Watts AD, Hunt NH, Wanigasekara Y, et al. A casein kinase I motif present in the cytoplasmic domain of members of the tumour necrosis factor ligand family is implicated in 'reverse signalling'. EMBO J. 1999;18(8):2119–26. doi: 10.1093/emboj/18.8.2119Watts AD, Hunt NH, Wanigasekara Y, et al. A casein kinase I motif present in the cytoplasmic domain of members of the tumour necrosis factor ligand family is implicated in 'reverse signalling'. EMBO J. 1999;18(8):2119–26. doi: 10.1093/emboj/18.8.2119Horiuchi T, Mitoma H, Harashima S, et al. Transmembrane TNF- α: structure, function and interaction with anti-TNF agents. Rheumatology (Oxford). 2010;49(7):1215–28. doi: 10.1093/rheumatology/keq031Horiuchi T, Mitoma H, Harashima S, et al. Transmembrane TNF- α: structure, function and interaction with anti-TNF agents. Rheumatology (Oxford). 2010;49(7):1215–28. doi: 10.1093/rheumatology/keq031Eissner G, Kolch W, Scheurich P. Ligands working as receptors: reverse signaling by members of the TNF superfamily enhance the plasticity of the immune system. Cytokine Growth Factor Rev. 2004;15(5):353–66. doi: 10.1016/j.cytogfr.2004.03.011Eissner G, Kolch W, Scheurich P. Ligands working as receptors: reverse signaling by members of the TNF superfamily enhance the plasticity of the immune system. Cytokine Growth Factor Rev. 2004;15(5):353–66. doi: 10.1016/j.cytogfr.2004.03.011Van Lent PL, Blom AB, Grevers L, et al. Toll-like receptor 4 induced FcgR expression potentiates early onset of joint inflammation and cartilage destruction during immune complex arthritis: Toll-like receptor 4 largely regulates FcgR expression by IL-10. Ann Rheum Dis. 2007;66(3):334–40. doi: 10.1136/ard.2006.057471Van Lent PL, Blom AB, Grevers L, et al. Toll-like receptor 4 induced FcgR expression potentiates early onset of joint inflammation and cartilage destruction during immune complex arthritis: Toll-like receptor 4 largely regulates FcgR expression by IL-10. Ann Rheum Dis. 2007;66(3):334–40. doi: 10.1136/ard.2006.057471Sandborn WJ, Lee SD, Randall C, et al. Long-term safety and efficacy of certolizumab pegol in the treatment of Crohn's disease: 7-ear results from PRECiSE 3 study. Aliment Pharmacol Ther. 2014;40(8):903–16. doi: 10.1111/apt.12930Sandborn WJ, Lee SD, Randall C, et al. Long-term safety and efficacy of certolizumab pegol in the treatment of Crohn's disease: 7-ear results from PRECiSE 3 study. Aliment Pharmacol Ther. 2014;40(8):903–16. doi: 10.1111/apt.12930Shen C, Assche GV, Colpaert S, et al. Adalimumab induces apoptosis of human monocytes: a comparative study with infliximab and etanercept. Aliment Pharmacol Ther. 2005;21(3):251–8. doi: 10.1111/j.1365-2036.2005.02309.xShen C, Assche GV, Colpaert S, et al. Adalimumab induces apoptosis of human monocytes: a comparative study with infliximab and etanercept. Aliment Pharmacol Ther. 2005;21(3):251–8. doi: 10.1111/j.1365-2036.2005.02309.xKeystone E, Landewe R, van Volenhoven R, et al. Long-term safety and efficacy of certolizumab pegol in the treatment of rheumatoid arthritis: 5 year results from the RAPID 1 trial and open-label extansion. Ann Rheum Dis. 2014;73(12):2094–100. doi: 10.1136/annrheumdis-2013-203695Keystone E, Landewe R, van Volenhoven R, et al. Long-term safety and efficacy of certolizumab pegol in the treatment of rheumatoid arthritis: 5 year results from the RAPID 1 trial and open-label extansion. Ann Rheum Dis. 2014;73(12):2094–100. doi: 10.1136/annrheumdis-2013-203695Sieper J, Landewe R, Rudwaleit M, et al. Effect of certolizumab pegol over ninty-six weeks in patients with axial spondyloarthritis: results from a Phase 3 randomized trial. Arthritis Rheum. 2015;67(3):668–77. doi: 10.1002/art.38973Sieper J, Landewe R, Rudwaleit M, et al. Effect of certolizumab pegol over ninty-six weeks in patients with axial spondyloarthritis: results from a Phase 3 randomized trial. Arthritis Rheum. 2015;67(3):668–77. doi: 10.1002/art.38973Landewe R, Braun J, Deodhar A, et al. Efficacy of Certolizumab Pegol on signs and symptoms of axial spondyloarthritis, including ankylosing spondyltitis: 24-week results of a double-blind randomized placebo-controlled Phase 3 study. Ann Rheum Dis. 2014;73(1):39–47. doi: 10/1136/annrheumdis- 2013-2024231Landewe R, Braun J, Deodhar A, et al. Efficacy of Certolizumab Pegol on signs and symptoms of axial spondyloarthritis, including ankylosing spondyltitis: 24-week results of a double-blind randomized placebo-controlled Phase 3 study. Ann Rheum Dis. 2014;73(1):39–47. doi: 10/1136/annrheumdis- 2013-2024231Reich K, Ortonne JP, Gottlieb AB, et al. Successful treatment of moderate to severe plaque psoriasis with the pegylated fab' certolizumab pegol: results of a phase II randomized, placebo-controlled trial with a re-treatment extension. Br J Dermatol. 2012;167(1):180–90. doi: 10.1111/j.1365-2133.2012.10941.x 26. Mease PJ, Fleischmann RM, Deodhar A, et al. Effect of certolizumab pegol on signs and symptoms in patients with psoriatic arthritis with and without prior anti-TNF exposure: 24 week results of a phase 3 double-blind randomized placebo-controlled study (RAPID-PsA). Ann Rheum Dis. 2014;73(1):48–55. doi: 10/1136/annrheumdis-2013-203696Reich K, Ortonne JP, Gottlieb AB, et al. Successful treatment of moderate to severe plaque psoriasis with the pegylated fab' certolizumab pegol: results of a phase II randomized, placebo-controlled trial with a re-treatment extension. Br J Dermatol. 2012;167(1):180–90. doi: 10.1111/j.1365-2133.2012.10941.x 26. Mease PJ, Fleischmann RM, Deodhar A, et al. Effect of certolizumab pegol on signs and symptoms in patients with psoriatic arthritis with and without prior anti-TNF exposure: 24 week results of a phase 3 double-blind randomized placebo-controlled study (RAPID-PsA). Ann Rheum Dis. 2014;73(1):48–55. doi: 10/1136/annrheumdis-2013-203696Mease PJ, Fleischmann R, Wollenhaupt J, et al. Long-term safety and efficacy of certolizumab pegol in patients with psoriatic arthritis with and without prior anti-tumor necrosis factor exposure: 96-week outcomes from the RAPID-PSA trial. Ann Rheum Dis. 2014;73(Suppl 2):90. doi: 10.1136/annrheumdis-2014-eular.1652Mease PJ, Fleischmann R, Wollenhaupt J, et al. Long-term safety and efficacy of certolizumab pegol in patients with psoriatic arthritis with and without prior anti-tumor necrosis factor exposure: 96-week outcomes from the RAPID-PSA trial. Ann Rheum Dis. 2014;73(Suppl 2):90. doi: 10.1136/annrheumdis-2014-eular.1652Gladman D, Fleishmann R, Coteur G, et al. Effect of Certolizumab Pegol on multiple facets of psoriatic arthritis as reported by patients: 24-week patient-reported outcome results of a phase III, multicenter study. Arthritis Care Res. 2014;66(7):1085–92. doi: 10.1002/acr. 22256Gladman D, Fleishmann R, Coteur G, et al. Effect of Certolizumab Pegol on multiple facets of psoriatic arthritis as reported by patients: 24-week patient-reported outcome results of a phase III, multicenter study. Arthritis Care Res. 2014;66(7):1085–92. doi: 10.1002/acr. 22256Kavanaugh A, Gladman D, van der Heijde D, et al. Improvements on productivity at paid work and within the household and increased participation in daily activities after 24 weeks of certolizumab pegol treatment of patients with psoriatic arthritis: results of a phase 3 double-blind randomized placebo-controlled study. Ann Rheum Dis. 2015;74:44–51. doi: 10/1136/annrheumdis- 2014-205198Kavanaugh A, Gladman D, van der Heijde D, et al. Improvements on productivity at paid work and within the household and increased participation in daily activities after 24 weeks of certolizumab pegol treatment of patients with psoriatic arthritis: results of a phase 3 double-blind randomized placebo-controlled study. Ann Rheum Dis. 2015;74:44–51. doi: 10/1136/annrheumdis- 2014-205198Van der Heijde D, Fleischmann R, Wollenhaupt J, et al. Effect of different imputation approaches on the evaluation of radiographic progression in patients with psoriatic arthritis: results of the RAPID-PsA 24-week phase III double-blind randomized placebocontrolled study of certolizumab pegol. Ann Rheum Dis. 2014;73:233–7. doi: 10.1136/annrheumdis-2013-203697Van der Heijde D, Fleischmann R, Wollenhaupt J, et al. Effect of different imputation approaches on the evaluation of radiographic progression in patients with psoriatic arthritis: results of the RAPID-PsA 24-week phase III double-blind randomized placebocontrolled study of certolizumab pegol. Ann Rheum Dis. 2014;73:233–7. doi: 10.1136/annrheumdis-2013-203697

The authors declare that there are no conflicts of interest present.