mrjСовременная ревматологияModern Rheumatology Journal1996-70122310-158XIMA-PRESS, LLC10.14412/1996-7012-2014-4-17-24mrj-570Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL INVESTIGATIONSИнгибитор интерлейкина 1 канакинумаб в лечении криопирин-ассоциированных периодических синдромов (CAPS). Клинический опытThe interleukin 1 inhibitor canakinumab in the treatment of cryopyrin-associated periodic syndromes (CAPS): clinical experienceСалугинаСветлана ОлеговнаSaluginaSvetlana Olegovna

Москва, Россия, 115522, Москва, Каширское шоссе, д. 34А

 

Moscow, Russia, 34A, Kashirskoe Shosse, Moscow 115522

pafon1@yandex.ruФедоровЕ. С.FedorovE. S.

Москва, Россия, 115522, Москва, Каширское шоссе, д. 34А

 

Moscow, Russia, 34A, Kashirskoe Shosse, Moscow 115522

pafon1@yandex.ruКузьминаН. Н.KuzminaN. N.

Москва, Россия, 115522, Москва, Каширское шоссе, д. 34А

 

Moscow, Russia, 34A, Kashirskoe Shosse, Moscow 115522

pafon1@yandex.ruЗахароваЕ. Ю.ZakharovaE. Yu.

Москва, Россия, 115478, Москва, ул. Москворечье, д. 1

Moscow, Russia, 1, Moskvorechye St., Moscow 115478

pafon1@yandex.ruФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»РоссияV.A. Nasonova Research Institute of RheumatologyRussian FederationФГБУ «Медико-генетический научный центр» РАМНРоссияResearch Center of Medical Genetics, Russian Academy of Medical GeneticsRussian Federation201403122014841724Copyright © Салугина С.О., Федоров Е.С., Кузьмина Н.Н., Захарова Е.Ю., 20142014Салугина С.О., Федоров Е.С., Кузьмина Н.Н., Захарова Е.Ю.Salugina S.O., Fedorov E.S., Kuzmina N.N., Zakharova 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://mrj.ima-press.net/mrj/article/view/570

Основным медиатором для криопирин-ассоциированных периодических синдромов (Сryopyrin Аssociated Рeriodic Syndrome – CAPS) является интерлейкин (ИЛ) 1β. В связи с этим в мире накапливается опыт применения ИЛ1-ингибиторов у пациентов с CAPS. Канакинумаб одобрен FDA и EMEA с 2009 г. для лечения CAPS, в Российской Федерации препарат зарегистрирован для применения при CAPS с 2011 г. Показана высокая эффективность и хорошая переносимость канакинумаба у пациентов с CAPS.

Цель исследования – представить российский опыт применения ИЛ1-ингибитора канакинумаба у детей с CAPS.

Материал и методы

Материал и методы. В исследование включено 6 пациентов с CAPS: 4 с Muckle – Wells Syndrome (MWS) и 2 с синдромом Chronic Infantile Onset Neurologic Cutneous Articular/Neonatal Onset Multisystem Inflammatory Disease (CINCA/NOMID), среди них было 5 больных женского пола в возрасте от 3,5 до 40 лет и 1 пациент мужского пола 17 лет. У 2 пациенток (дочери 17 лет и матери 40 лет) констатирован семейный случай MWS. Давность заболевания составила от 3,5 до 33 лет. У всех пациентов проведен молекулярно-генетический анализ на мутацию гена NLRP3(CIAS1). У 4 больных с MWS выявлены мутации Thr436Ile и Thr438Ile, у матери и дочери – Thr350Met, у 2 больных с CINCA/NOMID мутаций не обнаружено. На момент исследования 1 больная с MWS принимала глюкокортикоиды (ГК) в дозе 0,1 мг/кг, остальные получали симптоматическое лечение нестероидными противовоспалительными препаратами. Канакинумаб вводили каждые 8 нед подкожно в дозе 4 мг/кг при массе тела <15 кг, в дозе 2 мг/кг при массе тела >15 кг. К настоящему времени 2 больных с MWS получили 7 инъекций препарата (48 нед наблюдения), 2 больных с CINCA/NOMID – 6 инъекций (40 нед наблюдения) и 2 пациента с MWS – 2 иньекции (10 нед наблюдения).

Результаты исследования

Результаты исследования. У всех пациентов отмечено достоверное клиническое улучшение: нормализация самочувствия, купирование лихорадки, сыпи, глазных симптомов, снижение уровня острофазовых маркеров. Эффект сохранялся на протяжении всего периода наблюдения. У пациентки с MWS удалось полностью отменить ГК. Нежелательных явлений не выявлено ни в одном случае.

Выводы

Выводы. Опыт применения канакинумаба у пациентов с CAPS показал высокую эффективность и хорошую переносимость препарата. Более медленным оказалось снижение острофазовых маркеров у пациентов с синдромом CINCA/NOMID – наиболее тяжелой разновидностью CAPS.

Interleukin (IL) 1βis a major mediator of cryopyrin-associated periodic syndrome (CAPS). In this connection, the experience with IL-1 inhibitors used in patents with CAPS is being accumulated worldwide. Canakinumab was approved by FDA and EMEA in 2009 to treat CAPS and registered in the Russian Federation for this in 2011. The drug has been shown to be highly effective and well tolerated by patients with CAPS.

Objective

Objective: to present Russia's experience in using the IL-1 inhibitor canakinumab in children with CAPS.

Subjects and methods

Subjects and methods. The trial enrolled 6 CAPS patients, including 4 with Muckle-Wells Syndrome (MWS) and 4 with chronic infantile onset neurologic cutaneous articular/neonatal onset multisystem inflammatory disease (CINCA/NOMID), among whom there were 5 female patients aged 3.5 to 40 years and 1 male patient aged 17 years. Two patients (a 17-year-old daughter and her 40-year-old mother) were stated to have a familial MWS case. The duration of the disease was 3.5 to 33 years. All the patients underwent a molecular genetic analysis for mutations in the NLRP3 (CIAS1) gene. Four patients with MWS were found to have Thr436Ile and Thr438Ile mutations; the mother and her daughter had Thr350Met mutations; no mutations were detected in 2 patients with CINCA/NOMID. At the study, one female patient with MWS took gluco-corticoids (GC) in a dose of 0.1 mg/kg; the others received symptomatic therapy with nonsteroidal antiinflammatory drugs. Canakinumab was injected subcutaneously every 8 weeks in a dose of 4 mg/kg for patients with a body weight of <15 kg and in a dose of 2 mg/kg for those with a body weight of >15 kg. By now, 2 patients with MWS received 7 injections of the drug (a 48-week follow-up); 2 patients with CINCA/NOMID had its 6 injections (a 40-week follow-up) and 2 patients with MWS had 2 injections (a 10-week follow-up).

Results

Results. All the patients showed a significant clinical improvement: recovery; elimination of fever, rash, and eye symptoms; and a reduction in the levels of acute-phase markers. The effect retained throughout the follow-up. GC could be completely discontinued in the female patient with MWS. No adverse events were observed in any case.

Conclusion

Conclusion. The experience in using canakinumab in the patients with CAPS showed the high efficacy and good tolerability of the drug. The decrease in acute-phase markers was slower in the patients with CINCA/NOMID, the most severe form of CAPS.

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