Преимущества ингибитора ИЛ-17 иксекизумаба в терапии тяжелых форм псориаза

Псориаз – распространенное иммуноопосредованное заболевание, зачастую сопровождающееся воспалительными и метаболическими нарушениями. Около 20–30% пациентов страдают псориазом средней и тяжелой степени тяжести и нуждаются в применении системных методов лечения, которые включают традиционные, таргетные и генно-инженерные биологические препараты (ГИБП). При подборе биологического агента необходимо учитывать ряд факторов, связанных с заболеванием, пациентом и терапией. Важна оценка тяжести и активности, площади пораженных участков кожи, частоты рецидивов, зуда и других симптомов, а также наличие сопутствующих заболеваний, особенно псориатического артрита (ПсА). Наличие сопутствующей патологии, которая может способствовать или препятствовать применению ГИБП, является основным фактором, определяющим индивидуальную терапию. Персонализированное лечение подразумевает максимальную эффективность и минимальный риск побочных эффектов. Кроме того, существует возможность модифицировать течение болезни, вызывая длительную ремиссию и предотвращая развитие ПсА, что возможно в случае своевременного назначения ГИБТ. На сегодняшний день в арсенале дерматовенерологов представлены несколько классов ГИБП, среди которых наиболее высокой эффективностью и безопасностью обладают ингибиторы интерлейкинов (ИЛ). Препарат иксекизумаб является представителем группы ингибиторов ИЛ-17, моноклональным антителом класса IgG4, которое с высокой аффинностью и специфичностью связывается с ИЛ-17A. В рамках многочисленных клинических исследований и исследований реальной клинической практики препарат показал высокую эффективность и надежный профиль безопасности при лечении псориаза и ПсА, в т. ч. у пациентов с отягощенным коморбидным фоном, вовлечением тяжело поддающихся терапии локализаций. В представленной статье приведены ключевые данные исследований безопасности и эффективности терапии препаратом иксекизумаб, описан клинический случай успешного лечения пациента с псориазом и псориатической ониходистрофией. Своевременная инициация терапии способствовала остановке прогрессирования заболевания и существенно повысила качество жизни больного. Таким образом, представленные данные подтверждают преимущества применения препарата иксекизумаб в терапии псориаза.

1. Потекаев НН, Жукова ОВ, Артемьева СИ. Псориаз: персонифицированный подход к терапии. Предпочтительный выбор системных агентов с учетом коморбидных патологий. Медицинский совет. 2020;(12):28–34. https://doi.org/10.21518/2079-701X-2020-12-28-34.

2. Kim WB, Jerome D, Yeung J.. Can Fam Physician. 2017;63(4):278–285. Available at: https://pubmed.ncbi.nlm.nih.gov/28404701.

3. Lima XT, Minnillo R, Spencer JM, Kimball AB. Psoriasis prevalence among the 2009 AAD National Melanoma/Skin Cancer Screening Program participants. J Eur Acad Dermatol Venereol. 2013;27(6):680–685. https://doi.org/10.1111/j.1468-3083.2012.04531.x.

4. Parisi R, Symmons DP, Griffiths CE, Ashcroft DM; Identification and Management of Psoriasis and Associated ComorbidiTy (IMPACT) project team. Global epidemiology of psoriasis: a systematic review of incidence and prevalence. J Invest Dermatol. 2013;133(2):377–385. https://doi.org/10.1038/jid.2012.339.

5. Lebwohl MG, Kavanaugh A, Armstrong AW, Van Voorhees AS. US Perspectives in the Management of Psoriasis and Psoriatic Arthritis: Patient and Physician Results from the Population-Based Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) Survey. Am J Clin Dermatol. 2016;17(1):87–97. https://doi.org/10.1007/s40257-015-0169-x.

6. Ocampo DV, Gladman D. Psoriatic arthritis. F1000Res. 2019;8:F1000 Faculty Rev-1665. https://doi.org/10.12688/f1000research.19144.1.

7. Menter A. Psoriasis and psoriatic arthritis overview. Am J Manag Care. 2016;22(8 Suppl):s216–s224. Available at: https://pubmed.ncbi.nlm.nih.gov/27356193.

8. Alinaghi F, Calov M, Kristensen LE, Gladman DD, Coates LC, Jullien D et al. Prevalence of psoriatic arthritis in patients with psoriasis: A systematic review and meta-analysis of observational and clinical studies. J Am Acad Dermatol. 2019;80(1):251–265.e19. https://doi.org/10.1016/j.jaad.2018.06.027.

9. Kwan Z, Bong YB, Tan LL, Lim SX, Yong ASW, Ch’ng CC, Tan MP, Ismail R. Determinants of quality of life and psychological status in adults with psoriasis. Arch Dermatol Res. 2018;310(5):443–451. https://doi.org/10.1007/s00403-018-1832-x.

10. Puig L, Thom H, Mollon P, Tian H, Ramakrishna GS. Clear or almost clear skin improves the quality of life in patients with moderate-to-severe psoriasis: a systematic review and meta-analysis. J Eur Acad Dermatol Venereol. 2017;31(2):213–220. https://doi.org/10.1111/jdv.14007.

11. Bulat V, Šitum M, Delaš Aždajić M, Lovrić I, Dediol I. Study on the Impact of Psoriasis on Quality of Life: Psychological, Social and Financial Implications. Psychiatr Danub. 2020;32(Suppl. 4):553–561. Available at: https://pubmed.ncbi.nlm.nih.gov/33212463.

12. Husni ME. Comorbidities in Psoriatic Arthritis. Rheum Dis Clin North Am. 2015;41(4):677–698. https://doi.org/10.1016/j.rdc.2015.07.008.

13. Liu L, Lu J, Allan BW, Tang Y, Tetreault J, Chow CK et al. Generation and characterization of ixekizumab, a humanized monoclonal antibody that neutralizes interleukin-17A. J Inflamm Res. 2016;9:39–50. https://doi.org/10.2147/JIR.S100940.

14. Krueger JG, Fretzin S, Suarez-Farinas M, Haslett PA, Phipps KM, Cameron GS, et al. IL-17A is essential for cell activation and inflammatory gene circuits in subjects with psoriasis. J Allergy Clin Immunol. 2012;130(1):145–154e9. https://doi.org/10.1016/J.JACI.2012.04.024.

15. Griffiths CE, Reich K, Lebwohl M, van de Kerkhof P, Paul C, Menter A et al.; UNCOVER-2 and UNCOVER-3 investigators. Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials. Lancet. 2015;386(9993):541–551. https://doi.org/10.1016/S0140-6736(15)60125-8.

16. Gordon KB, Blauvelt A, Papp KA, Langley RG, Luger T, Ohtsuki M et al.; UNCOVER-1 Study Group; UNCOVER-2 Study Group; UNCOVER-3 Study Group. Phase 3 Trials of Ixekizumab in Moderate-to-Severe Plaque Psoriasis. N Engl J Med. 2016;375(4):345–356. https://doi.org/10.1056/NEJMoa1512711.

17. Papp KA, Leonardi CL, Blauvelt A, Reich K, Korman NJ, Ohtsuki M et al. Ixekizumab treatment for psoriasis: integrated efficacy analysis of three double-blinded, controlled studies (UNCOVER-1, UNCOVER-2, UNCOVER-3). Br J Dermatol. 2018;178(3):674–681. https://doi.org/10.1111/bjd.16050.

18. Blauvelt A, Papp K, Gottlieb A, Jarell A, Reich K, Maari C et al.; IXORA-R Study Group. A head-to-head comparison of ixekizumab vs. guselkumab in patients with moderate-to-severe plaque psoriasis: 12-week efficacy, safety and speed of response from a randomized, double-blinded trial. Br J Dermatol. 2020;182(6):1348–1358. https://doi.org/10.1111/bjd.18851.

19. Blauvelt A, Leonardi C, Elewski B, Crowley JJ, Guenther LC, Gooderham M et al.; IXORA-R Study Group. A head-to-head comparison of ixekizumab vs. guselkumab in patients with moderate-to-severe plaque psoriasis: 24-week efficacy and safety results from a randomized, double-blinded trial. Br J Dermatol. 2021;184(6):1047–1058. https://doi.org/10.1111/bjd.19509.

20. Paul C, Griffiths CEM, van de Kerkhof PCM, Puig L, Dutronc Y, Henneges C et al. Ixekizumab provides superior efficacy compared with ustekinumab over 52 weeks of treatment: Results from IXORA-S, a phase 3 study. J Am Acad Dermatol. 2019;80(1):70–79.e3. https://doi.org/10.1016/J.JAAD.2018.06.039.

21. Reich K, Pinter A, Lacour JP, Ferrandiz C, Micali G, French LE et al.; IXORA-S investigators. Comparison of ixekizumab with ustekinumab in moderate-to-severe psoriasis: 24-week results from IXORA-S, a phase III study. Br J Dermatol. 2017;177(4):1014–1023. https://doi.org/10.1111/bjd.15666.

22. Mease PJ, van der Heijde D, Ritchlin CT, Okada M, Cuchacovich RS, Shuler C et al.; SPIRIT-P1 Study Group. Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1. Ann Rheum Dis. 2017;76(1):79–87. https://doi.org/10.1136/annrheumdis-2016-209709.

23. Nash P, Kirkham B, Okada M, Rahman P, Combe B, Burmester GR et al.; SPIRIT-P2 Study Group. Ixekizumab for the treatment of patients with active psoriatic arthritis and an inadequate response to tumour necrosis factor inhibitors: results from the 24-week randomised, double-blind, placebo-controlled period of the SPIRIT-P2 phase 3 trial. Lancet. 2017;389(10086):2317–2327. https://doi.org/10.1016/S0140-6736(17)31429-0.

24. Smolen JS, Mease P, Tahir H, Schulze-Koops H, de la Torre I, Li L et al. Multicentre, randomised, open-label, parallel-group study evaluating the efficacy and safety of ixekizumab versus adalimumab in patients with psoriatic arthritis naïve to biological disease-modifying antirheumatic drug: final results by week 52. Ann Rheum Dis. 2020;79(10):1310–1319. https://doi.org/10.1136/annrheumdis-2020-217372.

25. Mease PJ, Smolen JS, Behrens F, Nash P, Liu Leage S, Li L et al.; SPIRIT H2H study group. A head-to-head comparison of the efficacy and safety of ixekizumab and adalimumab in biological-naïve patients with active psoriatic arthritis: 24-week results of a randomised, open-label, blinded-assessor trial. Ann Rheum Dis. 2020;79(1):123–131. https://doi.org/10.1136/annrheumdis-2019-215386.

26. Reich K, Kristensen LE, Smith SD, Rich P, Sapin C, Leage S et al. Efficacy and Safety of Ixekizumab Versus Adalimumab in Biologic-naïve Patients With Active Psoriatic Arthritis and Moderate-to-severe Psoriasis: 52-week Results From the Randomized SPIRIT-H2H Trial. Dermatol Pract Concept. 2022;12(2):e2022104. https://doi.org/10.5826/dpc.1202a104.

27. Cinelli E, Fabbrocini G, Megna M. Real-world experience versus clinical trials: pros and cons in psoriasis therapy evaluation. Int J Dermatol. 2022; 61(3):e107-e108. https://doi.org/10.1111/ijd.15644.

28. Lockshin B, Cronin A, Harrison RW, McLean RR, Anatale-Tardiff L, Burge R et al. Drug survival of ixekizumab, TNF inhibitors, and other IL-17 inhibitors in real-world patients with psoriasis: The Corrona Psoriasis Registry. Dermatol Ther. 2021;34(2):e14808. https://doi.org/10.1111/dth.14808.

29. Grace E, Zhu B, Malley W, O’Brien J, Mangner R, Agada N et al. Safety events occurring among patients exposed to ixekizumab in the Corrona Psoriasis Registry. In: 6th Congress of the Skin Inflammation and Psoriasis International Network; 25–27 April 2019; Paris, France. J Eur Acad Dermatol Venereol. 2019;33(Suppl 3):P001. https://doi.org/10.1111/jdv.15512.

30. Blauvelt A, Shi N, Burge R, Malatestinic WN, Lin CY, Lew CR et al. Comparison of real-world treatment patterns among patients with psoriasis prescribed ixekizumab or secukinumab. J Am Acad Dermatol. 2020;82(4):927–935. https://doi.org/10.1016/j.jaad.2019.11.015.

31. Caldarola G, Mariani M, Pirro F, Nicolotti N, Burlando M, Calabrese L et al. Comparison of short- and long-term effectiveness of ixekizumab and secukinumab in real-world practice. Expert Opin Biol Ther. 2021;21(2):279–286. https://doi.org/10.1080/14712598.2021.1849133.

32. Graier T, Salmhofer W, Jonak C, Weger W, Kölli C, Gruber B et al. Biologic drug survival rates in the era of anti-interleukin-17 antibodies: a time-period-adjusted registry analysis. Br J Dermatol. 2021;184(6):1094–1105. https://doi.org/10.1111/bjd.19701.

33. Sherman S, Zloczower O, Noyman Y, Amitay-Laish I, Hodak E, Pavlovsky L. Ixekizumab Survival in Heavily Pretreated Patients with Psoriasis: A Two-year Single-centre Retrospective Study. Acta Derm Venereol. 2020;100(19):adv00349. https://doi.org/10.2340/00015555-3714.

34. Rivera R, Velasco M, Vidal D, Carrascosa JM, Daudén E, Vilarrasa E et al. The effectiveness and safety of ixekizumab in psoriasis patients under clinical practice conditions: A Spanish multicentre retrospective study. Dermatol Ther. 2020;33(6):e14066. https://doi.org/10.1111/dth.14066.

35. Gulliver W, Penney M, Power R, Gulliver S, Montmayeur S, Burge R. Moderate-to-severe plaque psoriasis patients treated with ixekizumab: early real-world outcomes and adverse events. J Dermatolog Treat. 2022;33(1):354–360. https://doi.org/10.1080/09546634.2020.1755009.

36. Deza G, Notario J, Lopez-Ferrer A, Vilarrasa E, Ferran M, Del Alcazar E et al. Initial results of ixekizumab efficacy and safety in real-world plaque psoriasis patients: a multicentre retrospective study. J Eur Acad Dermatol Venereol. 2019;33(3):553–559. https://doi.org/10.1111/jdv.15288.

37. Magdaleno-Tapial J, Carmena-Ramón R, Valenzuela-Oñate C, Ortiz-Salvador JM, Sabater-Abad J, Hernández-Bel P et al. Efficacy and Safety of Ixekizumab in a Real-Life Practice: A Retrospective Bicentric Study. Actas Dermosifiliogr (Engl Ed). 2019;110(7):585–589. (In English, Spanish) https://doi.org/10.1016/j.ad.2019.02.006.

38. Chiricozzi A, Burlando M, Caldarola G, Conti A, Damiani G, De Simone C et al. Ixekizumab Effectiveness and Safety in the Treatment of Moderate-to-Severe Plaque Psoriasis: A Multicenter, Retrospective Observational Study. Am J Clin Dermatol. 2020;21:441–447. https://doi.org/10.1007/s40257-019-00490-2.

39. Damiani G, Conic RRZ, Pigatto PDM, Bragazzi NL, Pacifico A, Malagoli P; Young Dermatologists Italian Network. From randomized clinical trials to real life data. An Italian clinical experience with ixekizumab and its management. Dermatol Ther. 2019;32(3):e12886. https://doi.org/10.1111/dth.12886.

40. Conti A, Peccerillo F, Amerio P, Balato A, Bardazzi F, Bianchi L et al. Efficacy and safety of switching to ixekizumab in secukinumab nonresponder patients with psoriasis: results from a multicentre experience. Br J Dermatol. 2019;180(6):1547–1548. https://doi.org/10.1111/bjd.17580.

41. Sherman S, Solomon Cohen E, Amitay-Laish I, Hodak E, Pavlovsky L. IL-17A Inhibitor Switching – Efficacy of Ixekizumab Following Secukinumab Failure. A Single-center Experience. Acta Derm Venereol. 2019;99(9):769–773. https://doi.org/10.2340/00015555-3200.

42. Shahriari M, Harrison RW, Burge R, Lin CY, Malatestinic WN, Goldblum OM et al. Disease response and patient-reported outcomes among initiators of ixekizumab. J Dermatolog Treat. 2022;33(3):1538–1546. https://doi.org/10.1080/09546634.2020.1853023.

43. Georgakopoulos JR, Lam K, Sandhu VK, Ighani A, Phung M, Piguet V, Yeung J. Comparative 12-week effectiveness and safety outcomes of biologic agents ustekinumab, secukinumab and ixekizumab for the treatment of plaque psoriasis: a real-world multicenter retrospective study. J Eur Acad Dermatol Venereol. 2020;34(8):e416-e418. https://doi.org/10.1111/jdv.16366.

44. Shahriari M, Crabtree M, Burge R, Lin C, Malatestinic W, Goldblum O et al. Patient-reported outcomes and response to treatment for patients initiating ixekizumab: Findings from the Corrona Registry. J Am Acad Dermatol. 2019;81(4 Suppl.):AB252. https://doi.org/10.1016/j.jaad.2019.06.1118.

45. Leonardi C, Gara A, Amato D, Setayeshgar S, Wang S, Murage M et al. Disease severity and quality of life among ixekizumab-treated psoriasis patients in the real-world setting: Results from a single US dermatology referral practice. J Am Acad Dermatol. 2019;81(4 Suppl. 1):AB47. https://doi.org/10.1016/j.jaad.2019.06.206.

46. Craig L, Tao R, Setayeshgar S, Wang S, McMullen S, Burge R et al. 14216 Long-term treatment effects of ixekizumab among psoriasis patients who achieved early high-level treatment outcomes in a real-world setting: Results from a single US dermatology referral practice. J Am Acad Dermatol. 2020;83(6 Suppl.):AB133. https://doi.org/10.1016/j.jaad.2020.06.621.

47. Andrew B, Zhu B, Murage M, Guo J, Ridenour T, Shan M et al. 26654 Ixekizumab demonstrates greater medication adherence, persistence, and longer monotherapy duration than secukinumab, adalimumab, ustekinumab, and etanercept up to 3 years in the treatment of psoriasis: Real-world results. J Am Acad Dermatol. 2021;85(3 Suppl.):AB111. https://doi.org/10.1016/j.jaad.2021.06.463.

48. Feldman SR, Zhang J, Martinez DJ, Lopez-Gonzalez L, Marchlewicz EH, Shrady G et al. Real-world biologic and apremilast treatment patterns and healthcare costs in moderate-to-severe plaque psoriasis. Dermatol Online J. 2021;27(1):2. https://doi.org/10.5070/D3271052018.

49. Wu JJ, Zhu B, Burge R, Goldblum O, Choong C, Edson-Heredia E, Amatoet D Real world use of ixekizumab is associated with reductions in concomitant medications among biologic-experienced or biologic-naive patients with psoriasis. J Am Acad Dermatol. 2019;81(4 Suppl. 1):AB114. https://doi.org/10.1016/j.jaad.2019.06.437.

50. Pinter A, Costanzo A, Khattri S, Smith SD, Carrascosa JM, Tada Y et al. Comparative Effectiveness and Durability of Biologics in Clinical Practice: Month 12 Outcomes from the International, Observational Psoriasis Study of Health Outcomes (PSoHO). Dermatol Ther (Heidelb). 2023. https://doi.org/10.1007/s13555-023-01086-9.