vspВопросы современной педиатрииCurrent Pediatrics1682-55271682-5535Издательство «ПедиатрЪ»10.15690/vsp.v17i1.1858vsp-1868Research ArticleОРИГИНАЛЬНАЯ СТАТЬЯORIGINAL ARTICLESЭФФЕКТИВНОСТЬ И БЕЗОПАСНОСТЬ ФЕРМЕНТОЗАМЕСТИТЕЛЬНОЙ ТЕРАПИИ У ДЕТЕЙ С МУКОПОЛИСАХАРИДОЗАМИ I, II И VI ТИПОВ: ОДНОЦЕНТРОВОЕ КОГОРТНОЕ ИССЛЕДОВАНИЕEFFICACY AND SAFETY OF ENZYME REPLACEMENT THERAPY IN CHILDREN WITH MUCOPOLYSACCHARIDOSIS TYPE I, II, AND VI: A SINGLE-CENTER COHORT STUDYhttps://orcid.org/0000-0002-6545-4121ОсиповаЛ. А.OsipovaLiliia A.

Осипова Лилия Александровна - врач-невролог консультативного отделения КДЦ НМИЦ здоровья детей.

119991, Москва, Ломоносовский пр-т, д. 2, стр. 1,  тел.: +7 (495) 967-14-20

osipova_la@nczd.ruhttps://orcid.org/0000-0002-9562-3774КузенковаЛ. М.KuzenkovaLudmila M.https://orcid.org/0000-0002-2209-7531Намазова-БарановаЛ. С.Namazova-BaranovaLeyla S.

Москва

ГеворкянА. К.GevorkyanAnait K.

Москва

ПодклетноваТ. В.PodkletnovaTatiana V.

Москва

https://orcid.org/0000-0001-8077-5313МаянскийН. А.MayanskiyNikolay A.

Москва

РевуненковГ. В.RevunenkovGrigoriy V.

Москва

https://orcid.org/0000-0001-8320-2027ВашакмадзеН. Д.VashakmadzeNato D.

Москва

Национальный медицинский исследовательский центр здоровья детейРоссияNational Medical Research Center of Children’s HealthRussian FederationНациональный медицинский исследовательский центр здоровья детей; Первый Московский государственный медицинский университет им. И.М. Сеченова (Сеченовский Университет)РоссияNational Medical Research Center of Children’s Health; Sechenov First Moscow State Medical UniversityRussian FederationНациональный медицинский исследовательский центр здоровья детей; Российский национальный исследовательский медицинский университет им. Н.И. ПироговаРоссияNational Medical Research Center of Children’s HealthRussian FederationНациональный медицинский исследовательский центр здоровья детей; Российский национальный исследовательский медицинский университет им. Н.И. ПироговаРоссияNational Medical Research Center of Children’s Health; Pirogov Russian National Research Medical UniversityRussian Federation2018010420181717684Copyright © Осипова Л.А., Кузенкова Л.М., Намазова-Баранова Л.С., Геворкян А.К., Подклетнова Т.В., Маянский Н.А., Ревуненков Г.В., Вашакмадзе Н.Д., 20182018Осипова Л.А., Кузенкова Л.М., Намазова-Баранова Л.С., Геворкян А.К., Подклетнова Т.В., Маянский Н.А., Ревуненков Г.В., Вашакмадзе Н.Д.Osipova L.A., Kuzenkova L.M., Namazova-Baranova L.S., Gevorkyan A.K., Podkletnova T.V., Mayanskiy N.A., Revunenkov G.V., Vashakmadze N.D.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vsp.spr-journal.ru/jour/article/view/1868

Имеются ограниченные данные об эффективности длительной ферментозаместительной терапии (ФЗТ) у детей с мукополисахаридозами (МПС).

Цель исследования

Цель исследования: изучить эффективность и безопасность длительной ФЗТ у детей с МПС I, II и VI типов.

Методы

Методы. Проанализированы результаты ФЗТ препаратами ларонидаза, идурсульфаза и галсульфаза у детей с МПС I, II и VI типов, госпитализированных в федеральный научно-исследовательский центр с января 2007 по ноябрь 2016 г. Эффективность терапии оценивали по уровню нормализованной экскреции гликозаминогликанов (ГАГ) с мочой (отношение концентрации ГАГ к креатинину мочи), пересчитанному в процентах (%) превышения верхней границы нормы для соответствующего возраста. Данные о проводимой терапии и ее результатах, включая нежелательные явления, извлечены из медицинских карт стационарных больных.

Результаты

Результаты. Результаты лечения (внутривенные инфузии, интервалы между введениями от 4 до 10 сут) изучены у 33 детей (из них 5 девочек) с МПС I (n = 4; ларонидаза в дозе 0,58 мг/кг), II (n = 26; идурсульфаза в дозе 0,5 мг/кг) и VI (n = 3; галсульфаза в дозе 1 мг/кг) типов. На фоне ФЗТ продолжительностью (медиана) 27 (14; 41) мес отмечено снижение нормализованной экскреции ГАГ с мочой с 376% (172; 791) до 54% (0; 146) превышения верхней границы возрастной нормы (p < 0,001). Снижение нормализованной экскреции ГАГ ниже верхней границы возрастной нормы установлено у 12/33 (36%) пациентов. Связанные с ФЗТ нежелательные явления определены у 12 больных, в 1 случае потребовалось двукратное временное прекращение терапии. Впервые описано развитие на фоне ФЗТ нефротического синдрома у 2 пациентов с тяжелой формой МПС II.

Background

Background. There are limited data on the efficacy of long-term enzyme replacement therapy (ERT) in children with mucopolysaccharidosis (MPS).

Objective

Objective. Our aim was to study the efficacy and safety of long-term ERT in children with MPS type I, II, and VI.

Methods

Methods. We analyzed the results of ERT with laronidase, idursulfase, and galsulfase in children with MPS type I, II, and VI admitted to the federal research center from January 2007 to November 2016. The response rate was assessed by the level of normalized urinary excretion of glycosaminoglycans (GAGs) (the ratio of GAGs concentration to urine creatinine) recalculated in percent (%) exceedance of the upper limit of normal for the corresponding age. Data on the administered therapy and its results, including adverse events, is extracted from the medical records of in-patients.

Results

Results. The results of treatment (intravenous infusions, intervals between administrations from 4 to 10 days) were studied in 33 children (5 of them were girls) with MPS type I (n = 4; laronidase at a dose of 0.58 mg/kg), II (n = 26; idursulfase at a dose of 0.5 mg/kg), and VI (n = 3; galsulfase at a dose of 1 mg/kg). A decrease in the normalized urinary excretion of GAGs from 376% (172; 791) to 54% (0; 146) exceedance of the upper limit of normal for the age (p < 0.001) was noted in the course of ERT lasting (median) 27 (14; 41) months. A decrease in the normalized GAGs excretion below the upper limit of normal for the age was established in 12/33 (36%) patients. ERT-associated adverse events were identified in 12 patients; one case required a two-fold therapy interruption. The development of nephrotic syndrome in the course of ERT in patients with severe MPS II was first described.

Conclusion

Conclusion. Long-term ERT in children with MPS type I, II, and VI is characterized by acceptable efficacy and safety. Key words: children, mucopolysaccharidosis, enzyme replacement therapy, laronidase, idursulfase, galsulfase, glycosaminoglycans.

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