Pediatric Hematology/Oncology and ImmunopathologyPediatric Hematology/Oncology and ImmunopathologyВопросы гематологии/онкологии и иммунопатологии в педиатрии1726-17082414-9314Fund Doctors, Innovations, Science for Children76810.24287/1726-1708-2023-22-3-94-102ORIGINAL ARTICLESОРИГИНАЛЬНЫЕ СТАТЬИVelaglucerase alfa for treatment in children with Gaucher disease type 1: the Russian experienceОпыт применения велаглюцеразы альфа у детей с болезнью Гоше 1-го типа в Россииhttps://orcid.org/0000-0003-2881-4703MovsisyanG. B.МовсисянГ. Б.
Russian Federation

Goar B. Movsisyan - Cand. Med. Sci., a senior researcher at the Laboratory of Rare Hereditary Diseases in Children.

2, building 1, Lomonosovskiy Avenue, 119991, Moscow

Мовсисян Гоар Борисовна - кандидат медицинских наук, старший научный сотрудник лаборатории редких наследственных болезней у детей Медико-генетического центра.

119991, Москва, Ломоносовский просп., 2, стр. 1

movsisyan@nczd.ruhttps://orcid.org/0000-0003-4885-4171Savost`yanovK. V.СавостьяновК. В.
Russian Federation

Moscow

Москва

https://orcid.org/0000-0001-6648-2063PushkovA. A.ПушковА. А.
Russian Federation

Moscow

Москва

https://orcid.org/0000-0002-3473-2897MazanovaN. N.МазановаН. Н.
Russian Federation

Moscow

Москва

https://orcid.org/0009-0004-3134-9069KhazykovaJ. V.ХазыковаД. В.
Russian Federation

Moscow

Москва

https://orcid.org/0000-0002-5282-6504FirumyantsА. I.ФирумянцА. И.
Russian Federation

Moscow

Москва

https://orcid.org/0000-0003-4905-2373PotapovA. S.ПотаповА. С.
Russian Federation

Moscow

Москва

https://orcid.org/0000-0001-8586-7946FisenkoA. P.ФисенкоА. П.
Russian Federation

Moscow

Москва

National Medical Research Center for Children's Health of Ministry of Healthcare of the Russian FederationФГАУ «Национальный медицинский исследовательский центр здоровья детей» Минздрава РоссииThe I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of the Russian Federation (the Sechenov University)ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет)03102023223941020110202301102023Copyright ©; 2023, «D. Rogachev NMRCPHOI»Copyright ©; 2023, ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России2023«D. Rogachev NMRCPHOI»ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава Россииhttps://creativecommons.org/licenses/by/4.0https://hemoncim.com/jour/article/view/768

The current gold standard for the treatment of Gaucher disease type 1 in children is enzyme replacement therapy. The efficacy and safety of treatment with velaglucerase alfa have been assessed in only a few large studies involving pediatric patients as subjects of research. In the Russian literature, there are no data available on the use of velaglucerase alfa in drug-naïve patients with Gaucher disease type 1. The aim of our study was to assess the efficacy and safety of treatment with velaglucerase alfa in children with Gaucher disease type 1. The study was approved by the Independent Ethics Committee and the Scientific Council of the National Medical Research Center for Children's Health of Ministry of Healthcare of the Russian Federation. All patients and/or their legal representatives gave their informed consent to the study. The efficacy of treatment with velaglucerase alfa in children with Gaucher disease type 1 was assessed by analyzing monitoring data of 15 patients aged 2 to 15 years who had been registered in the Russian Pediatric Gaucher Registry established at National Medical Research Center for Children's Health of Ministry of Healthcare of Russia over the period from 2015 to 2023. None of the patients had ever undergone enzyme replacement therapy before they were included in this study. The median age at the start of treatment was 6.5 years. We analyzed the patients' anthropometric, laboratory and instrumental data at 0, 6, 12, 24 and 36 months. The initial dose of enzyme replacement therapy ranged from 30 to 60 units/kg (with the median of 43 units/kg per infusion) once every 2 weeks based on disease severity. In as little as 6 months after the initiation of therapy with velaglucerase alfa, patients with Gaucher disease type 1 showed a statistically significant improvement in all measured parameters (p < 0.001): normalization of the median hemoglobin concentration and platelet count (from 113 to 125 g/L and from 111 to 163 × 109/L, respectively); a reduction in degree of liver and spleen enlargement (in terms of volume, from 45.1 to 17.9% and from 39.4 to 15.5%, respectively); a reduction in degree of the right liver lobe enlargement (in terms of linear measurements, from 27.2 to 11.1%); a reduction in degree of spleen enlargement (in terms of its length and width, from 73.4 to 37.8% and from 60.3 to 17.5%, respectively). Our patients had a remarkable decrease in biomarker activity after 3 years of therapy: chitotriosidase activity decreased from 2699 to 227 nmol/mL/h and glucosylsphingosine level was reduced from 204.0 to 35.3 ng/mL (р < 0.001). There were no adverse events during the course of treatment. After 6 months and 1 year of regular enzyme replacement therapy with appropriate doses of velaglucerase alfa initiated in a timely manner, children with Gaucher disease type 1 achieve normal hemoglobin concentrations and platelet counts, a reduction in biomarker activity, and a decrease in liver and spleen volumes. After 3 years of enzyme replacement therapy, patients achieve their main therapeutic goals such as the resolution of anemia and thrombocytopenia, an almost complete regression of hepatosplenomegaly and the normalization of bone mineral density and height adjusted for age.

На современном этапе «золотым стандартом» лечения болезни Гоше 1-го типа у детей является ферментная заместительная терапия. Оценка эффективности и безопасности лечения велаглюцеразой альфа в педиатрической когорте больных ограничена лишь несколькими крупными исследованиями. В отечественной литературе не обнаружено публикаций по опыту применения велаглюцеразы альфа у «наивной» группы пациентов с болезнью Гоше 1-го типа. Цель исследования: оценить эффективность и безопасность применения велаглюцеразы альфа у детей с болезнью Гоше 1-го типа. Настоящее исследование одобрено независимым этическим комитетом и утверждено решением ученого совета ФГАУ «НМИЦ здоровья детей» Минздрава России. От пациентов и/или их законных представителей было получено информированное согласие на проведение исследования. Оценку эффективности терапии велаглюцеразой альфа у детей с болезнью Гоше 1-го типа проводили путем анализа данных мониторинга 15 пациентов в возрасте от 2 до 15 лет, занесенных в Российский педиатрический регистр болезни Гоше на базе ФГАУ «НМИЦ здоровья детей» Минздрава России в период 2015−2023 гг. Все пациенты на момент инициации лечения ранее не получали ферментную заместительную терапию. Медиана возраста начала лечения составила 6,5 года. Проводился учет антропометрических, лабораторных и инструментальных данных на точках 0, 6, 12, 24 и 36 мес. Доза ферментной заместительной терапии на момент инициации с учетом тяжести течения заболевания варьировала от 30 до 60 ЕД/кг с медианой 43 ЕД/кг на введение 1 раз в 2 нед. Уже через 6 мес от начала применения велаглюцеразы альфа у детей с болезнью Гоше 1-го типа отмечены статистически значимые улучшения всех показателей (p < 0,001): нормализация медианы концентрации гемоглобина (со 113 до 125 г/л) и количества тромбоцитов (со 111 до 163 × 109/л), сокращение степени увеличения объемов печени c 45,1 до 17,9% и селезенки с 39,4 до 15,5%, линейных размеров правой доли печени с 27,2 до 11,1%, длины и ширины селезенки с 73,4 до 37,8% и с 60,3 до 17,5% соответственно. При анализе активности биомаркеров гликозилсфингозина и хитотриозидазы уже через 1 год от начала терапии отмечено достоверное снижение значений, а к 3-му году лечения получено выраженное снижение медианы показателей с 204,0 (117,6; 359,2) до 35,3 (13,1; 133,6) нг/мл и с 2699 (1364; 8863,5) до 227 (287,5; 1367,5) нмоль/мл/ч соответственно (р < 0,001). Нежелательных явлений за период терапии не зарегистрировано. Таким образом, своевременно назначенная регулярная ферментная заместительная терапия велаглюцеразой альфа при адекватном режиме дозирования уже через 6 мес и 1 год от начала лечения позволяет достигнуть нормализации концентрации гемоглобина и количества тромбоцитов, снижения активности биомаркеров и сокращения увеличенных размеров печени и селезенки у детей с болезнью Гоше 1-го типа. К 3-му году лечения отмечается достижение ключевых целей терапии в виде купирования анемии и тромбоцитопении, практически полного регресса гепатоспленомегалии, нормализации денситометрических показателей минеральной плотности костей и длины тела по отношению к возрасту ребенка.

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Poster presented at the American Society of Human Genetics (ASHG) 62nd Annual meeting, November 6–10. San Francisco, CA, USA, 2012.