rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2018-722-726rsp-2648Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHНовые возможности в лечении псориаза и псориатического артритаNew opportunities in the treatment of psoriasis and psoriatic arthritisКубановА. А.KubanovA. A.

107076, Москва, ул. Короленко, 3, строение 6.

3, Korolenko St., Build. 6, Moscow 107076.

КарамоваА. Э.KaramovaA. E.

107076, Москва, ул. Короленко, 3, строение 6.

3, Korolenko St., Build. 6, Moscow 107076.

karamova@cnikvi.ruАртамоноваО. Г.ArtamonovaO. G.

107076, Москва, ул. Короленко, 3, строение 6.

3, Korolenko St., Build. 6, Moscow 107076.

ФГБУ «Государственный научный центр дерматовенерологии и косметологии» Минздрава России.РоссияState Research Center for Dermatovenereology and Cosmetology, Ministry of Health of Russia.Russian Federation201821012019566722726Copyright © Кубанов А.А., Карамова А.Э., Артамонова О.Г., 20192019Кубанов А.А., Карамова А.Э., Артамонова О.Г.Kubanov A.A., Karamova A.E., Artamonova O.G.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/2648

Цель исследования – оценить эффективность и безопасность селективного ингибитора фосфодиэстеразы 4-го типа у больных псориазом и псориатическим артритом (ПсА).Материал и методы. Проведено открытое неконтролируемое исследование. Включены 20 больных (12 мужчин, 8 женщин), средний возраст – 39,2±14,3 года, средняя длительность псориаза – 20,2±12,2 года, средняя длительность ПсА – 10,4±10,2 года. Все пациенты, включенные в исследование, ранее уже получали фототерапию, системные препараты (метотрексат, ароматические ретиноиды) – с недостаточным эффектом. Апремиласт назначался по стандартной схеме: титрование дозы в течение первых 5 дней, далее таблетки по 30 мг 2 раза в день в течение 26 нед. Оценку эффективности терапии проводили на 14-й и 26-й неделях по динамике индексов PASI, BSA, sPGA и по критериям Американской коллегии ревматологов (ACR), на 26-й неделе – по динамике индекса DAS28.Результаты и обсуждение. К 14-й неделе терапии было отмечено снижение PASI на 50% у 12 (60%) и на 75% у 5 (25%) пациентов, к 26-й неделе – соответственно у 14 (70%) и у 7 (35%) пациентов. На 14-й неделе 20% улучшение по критериям ACR было достигнуто у 14 (81,2%) больных. Индекс DAS28 на 26-й неделе уменьшился в среднем на 1,8. Неблагоприятные реакции (сильные головные боли, тахикардия) отмечались у двух больных, которые были исключены из исследования.Заключение. Апремиласт является эффективным и безопасным средством для лечения псориаза и ПсА у пациентов, которые ранее без эффекта получали другую системную терапию или плохо ее переносили.

Objective: to evaluate the efficacy and safety of a selective phosphodiesterase type 4 inhibitor in patients with psoriasis and psoriatic arthritis (PsA).Subjects and methods. An open uncontrolled study was conducted, which enrolled 20 patients (12 men, 8 women); their mean age was 39.2±14.3 years, the mean duration of psoriasis and PsA was 20.2±12.2 and 10.4±10.2 years, respectively. All the patients included in the study had previously received phototherapy, systemic drugs (methotrexate, aromatic retinoids) with an insufficient effect. Apremilast was administered according to the standard regimen: dose titration during the first 5 days, then 30-mg tablets twice daily for 26 weeks. The efficiency of the therapy was evaluated from changes in PASI, BSA, and sPGA and according to the American College of Rheumatology (ACR) criteria at 14 and 26 weeks and from those in DAS28 at 26 week.Results and discussion. There were 50 and 75% decreases in PASI respectively in 12 (60%) and 5 (25%) patients, at week 14 of therapy and in 14 (70%) and 7 (35%) patients at week 26. Fourteen (81.2%) patients achieved 20% ACR improvement at week 14. DAS28 decreased on an average by 1.8 at week 26. Adverse events (severe headache, tachycardia) were observed in two patients who were excluded from the study.Conclusion. Apremilast is an effective and safe agent for the treatment of psoriasis and PsA in patients who have received another systemic therapy proven to be ineffective or they tolerated the latter poorly.

псориазпсориатический артритсистемная терапияапремиластингибитор фосфодиэстеразы 4psoriasispsoriatic arthritissystemic therapyapremilastphosphodiesterase type 4 inhibitorReferencesКубанова АА и др., редакторы. Федеральные клинические рекомендации. Дерматовенерология 2015: Болезни кожи. Инфекции, передаваемые половым путем. Москва: Деловой экспресс; 2016. 768 с. [Kubanova AA et al., editors. Federal'nye klinicheskie rekomendatsii. Dermatovenerologiya 2015: Bolezni kozhi. Infektsii, peredavaemye polovym putem [Federal clinical guidelines. Dermatovenereology 2015: Diseases of the skin. Sexually Transmitted Infections]. Moscow: Delovoi ekspress; 2016. 768 p. (In Russ.)].Кубанова АА и др., редакторы. Федеральные клинические рекомендации. Дерматовенерология 2015: Болезни кожи. Инфекции, передаваемые половым путем. Москва: Деловой экспресс; 2016. 768 с. [Kubanova AA et al., editors. Federal'nye klinicheskie rekomendatsii. Dermatovenerologiya 2015: Bolezni kozhi. Infektsii, peredavaemye polovym putem [Federal clinical guidelines. Dermatovenereology 2015: Diseases of the skin. Sexually Transmitted Infections]. Moscow: Delovoi ekspress; 2016. 768 p. (In Russ.)].Gladman DD, Antoni C, Mease P, et al. Psoriatic arthritis epidemiology, clinical features, course, and outcome. Ann Rheum Dis. 2005;64 Suppl 2:ii14-7. doi: 10.1136/ard.2004.032482Gladman DD, Antoni C, Mease P, et al. Psoriatic arthritis epidemiology, clinical features, course, and outcome. Ann Rheum Dis. 2005;64 Suppl 2:ii14-7. doi: 10.1136/ard.2004.032482Taylor W, Gladman D, Helliwell P, et al. Classification criteria for psoriatic arthritis; development of new criteria from a large international study. Arthritis Rheum. 2006;54:2665-73. doi: 10.1002/art.21972Taylor W, Gladman D, Helliwell P, et al. Classification criteria for psoriatic arthritis; development of new criteria from a large international study. Arthritis Rheum. 2006;54:2665-73. doi: 10.1002/art.21972Федеральные клинические рекомендации по ведению больных псориатическим артритом. Доступно по ссылке: http://www.ismos.ru/guidelines/doc/psoriaticheskij_artrit.pdf [Federal'nye klinicheskie rekomendatsii po vedeniyu bol'nykh psoriaticheskim artritom [Federal clinical guidelines for the management of patients with psoriatic arthritis]. Available from: http://www.ismos.ru/guidelines/doc/psoriaticheskij_artrit.pdf (In Russ.)].Федеральные клинические рекомендации по ведению больных псориатическим артритом. Доступно по ссылке: http://www.ismos.ru/guidelines/doc/psoriaticheskij_artrit.pdf [Federal'nye klinicheskie rekomendatsii po vedeniyu bol'nykh psoriaticheskim artritom [Federal clinical guidelines for the management of patients with psoriatic arthritis]. Available from: http://www.ismos.ru/guidelines/doc/psoriaticheskij_artrit.pdf (In Russ.)].Wcislo-Dziadecka D, Zbiciak-Nylec M, Brzezinska-Wcislo L, et al. Newer treatments of psoriasis regarding IL23 inhibitors, phosphodiesterase 4 inhibitors, and Janus kinase inhibitors. Dermatol Ther. 2017;30(6):12555. doi: 10.1111/dth.12555Wcislo-Dziadecka D, Zbiciak-Nylec M, Brzezinska-Wcislo L, et al. Newer treatments of psoriasis regarding IL23 inhibitors, phosphodiesterase 4 inhibitors, and Janus kinase inhibitors. Dermatol Ther. 2017;30(6):12555. doi: 10.1111/dth.12555Schafer PH, Truzzi F, Parton A, et al. Phosphodiesterase 4 in inflammatory diseases: effects of apremilast in psoriatic blood and in dermal myofibroblasts through the PDE4/CD271 complex. Cell Signal. 2016;28(7):753-63. doi: 10.1016/j.cellsig.2016.01.007Schafer PH, Truzzi F, Parton A, et al. Phosphodiesterase 4 in inflammatory diseases: effects of apremilast in psoriatic blood and in dermal myofibroblasts through the PDE4/CD271 complex. Cell Signal. 2016;28(7):753-63. doi: 10.1016/j.cellsig.2016.01.007Papp K, Reich K, Leonardi CL, et al. Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (ESTEEM1). J Am Acad Dermatol. 2015;73:37-49. doi: 10.1016/j.jaad.2015.03.049Papp K, Reich K, Leonardi CL, et al. Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (ESTEEM1). J Am Acad Dermatol. 2015;73:37-49. doi: 10.1016/j.jaad.2015.03.049Edwards СJ, Blanco FJ, Crowley J, et al. Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: a phase III, randomised, controlled trial (PALACE 3). Ann Rheum Dis. 2016;75:1065-73. doi: 10.1136/annrheumdis-2015-207963Edwards СJ, Blanco FJ, Crowley J, et al. Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: a phase III, randomised, controlled trial (PALACE 3). Ann Rheum Dis. 2016;75:1065-73. doi: 10.1136/annrheumdis-2015-207963Edwards CJ, Blanco FJ, Crowley J, et al. Long-term (52-week) results of a phase 3, randomized, controlled trial of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement (PALACE 3). Arthritis Rheum. 2013;65(10 Suppl):S132.Edwards CJ, Blanco FJ, Crowley J, et al. Long-term (52-week) results of a phase 3, randomized, controlled trial of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement (PALACE 3). Arthritis Rheum. 2013;65(10 Suppl):S132.Pincelli C, Schafer PH, French LE, et al. Mechanisms underlying the clinical effects of apremilast for psoriasis. J Drugs Dermatol. 2018;17(8):835-40.Pincelli C, Schafer PH, French LE, et al. Mechanisms underlying the clinical effects of apremilast for psoriasis. J Drugs Dermatol. 2018;17(8):835-40.Galluzzo M, D’Adamio S, Campione E, et al. Treating a Multidrug-Resistant Psoriatic HLA-C*18:01 Allele Carrier with Combination Ustekinumab Apremilast Therapy. Mol Diagn Ther. 2018 (Pub Online: 03 Aug 2018). doi: 10.1007/s40291-018-0354-8Galluzzo M, D’Adamio S, Campione E, et al. Treating a Multidrug-Resistant Psoriatic HLA-C*18:01 Allele Carrier with Combination Ustekinumab Apremilast Therapy. Mol Diagn Ther. 2018 (Pub Online: 03 Aug 2018). doi: 10.1007/s40291-018-0354-8Kishimoto M, Komine M, Hioki T, et al. Real-world use of apremilast for patients with psoriasis in Japan. J Dermatol. 2018 (Pub Online: 31 Aug 2018). doi: 10.1111/1346-8138.14617Kishimoto M, Komine M, Hioki T, et al. Real-world use of apremilast for patients with psoriasis in Japan. J Dermatol. 2018 (Pub Online: 31 Aug 2018). doi: 10.1111/1346-8138.14617Ceccarelli F, Lucchetti R, Spinelli FR, et al. Early response to apremilast treatment in psoriatic arthritis: a real-life ultrasonographic follow-up study. Rheumatology. 2018;57(8):1490-1. doi: 10.1093/rheumatology/key145Ceccarelli F, Lucchetti R, Spinelli FR, et al. Early response to apremilast treatment in psoriatic arthritis: a real-life ultrasonographic follow-up study. Rheumatology. 2018;57(8):1490-1. doi: 10.1093/rheumatology/key145Wells AF, Edwards CJ, Kivitz AJ, et al. Apremilast monotherapy in DMARD-naive psoriatic arthritis patients: results of the randomized, placebo-controlled PALACE 4 trial. J Rheumatol. 2018;57:1253-63. doi: 10.1093/rheumatology/key032Wells AF, Edwards CJ, Kivitz AJ, et al. Apremilast monotherapy in DMARD-naive psoriatic arthritis patients: results of the randomized, placebo-controlled PALACE 4 trial. J Rheumatol. 2018;57:1253-63. doi: 10.1093/rheumatology/key032Lee EB, Amin M, Egeberg A, et al. Adverse events associated with apremilast use and withdrawal for psoriasis in a real-world setting. J Eur Acad Dermatol Venereol. 2016 Oct;32(10):e393-e394. doi: 10.1111/jdv.15061Lee EB, Amin M, Egeberg A, et al. Adverse events associated with apremilast use and withdrawal for psoriasis in a real-world setting. J Eur Acad Dermatol Venereol. 2016 Oct;32(10):e393-e394. doi: 10.1111/jdv.15061

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