urmjУральский медицинский журналUral Medical Journal2949-4389Ural State Medical University10.52420/umj.24.2.95WYHSSYurmj-1781Research ArticleОригинальные статьи | Original articlesOriginal articlesРезультаты сравнительной эффективности патогенетической терапии CFTR-модуляторами у детей с муковисцидозомResults of Comparative Effectiveness of Pathogenetic Therapy with CFTR Modulators in Children with Cystic Fibrosishttps://orcid.org/0009-0002-8869-108XВасенёваЮ. О.VasenyovaYu. O.

Юлия Олеговна Васенёва — ассистент кафедры госпитальной педиатрии, институт педиатрии и репродуктивной медицины, Уральский ГМУ; врач‑педиатр, пульмонолог детского консультативно‑диагностического центра, Областная ДКБ.

Екатеринбург

Yulia O. Vasenyova — Assistant of the Department of Hospital Pediatrics, Institute of Pediatrics and Reproductive Medicine, Ural State Medical University, Ekaterinburg, Russia; Pediatrician‑Pulmonologist of the Children’s Consultative and Diagnostic Center.

Ekaterinburg

yulya.vasenyova@yandex.ruhttps://orcid.org/0000-0002-5274-4699ВахловаИ. В.VakhlovaI. V.

Ирина Вениаминовна Вахлова — доктор медицинских наук, профессор, заведующий кафедрой госпитальной педиатрии, директор института педиатрии и репродуктивной медицины.

Екатеринбург

Irina V. Vakhlova — Doctor of Sciences (Medicine), Professor, Head of the Department of Hospital Pediatrics, Director of the Institute of Pediatrics and Reproductive Medicine.

Ekaterinburg

pediatria@usma.ruАверьяновО. Ю.AveryanovO. Yu.

Олег Юрьевич Аверьянов — главный врач.

Екатеринбург

Oleg Yu. Averyanov — Chief Physician.

Ekaterinburg

averianovoy@mis66.ruУральский государственный медицинский университет; Областная детская клиническая больницаРоссияUral State Medical University; Regional Children’s Clinical HospitalRussian FederationУральский государственный медицинский университетРоссияUral State Medical UniversityRussian FederationОбластная детская клиническая больницаРоссияRegional Children’s Clinical HospitalRussian Federation20250505202524295–108Copyright © Васенёва Ю.О., Вахлова И.В., Аверьянов О.Ю., 20252025Васенёва Ю.О., Вахлова И.В., Аверьянов О.Ю.Vasenyova Y.O., Vakhlova I.V., Averyanov O.Y.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.umjusmu.ru/jour/article/view/1781Обоснование

Обоснование. Значимым результатом развития фармакотерапии муковисцидоза является стратегия, направленная на восстановление структуры и нормальной функции белка CFTR. Вопрос сравнительной эффективности CFTR-модуляторов требует изучения для обеспечения дифференцированного подхода при назначении терапии.

Цель — провести оценку эффективности терапии CFTR-модуляторами у детей с муковисцидозом.

Материалы и методы

Материалы и методы. Проведено открытое проспективное сравнительное нерандомизированное исследование в период с декабря 2022 г. по ноябрь 2023 г. В исследовании принял участие 81 пациент с установленным муковисцидозом в возрасте 2–17 лет: 35 пациентов получали CFTR-модулятор элексакафтор/тезакафтор/ивакафтор (тройная терапия); 23 — CFTR-модулятор ивакафтор/лумакафтор (двойная терапия); 23 ребенка составили контрольную группу, не получавшую CFTR-модуляторы. Обследование проводилось на старте и через 12 мес. наблюдения. Оценка эффективности терапии проводилась через 12 мес. на основании сравнительного анализа полученных результатов между двумя группами, получавшими CFTR-модуляторы, и контрольной группой.

Результаты

Результаты. На фоне тройной терапии CFTR-модуляторами выявлено статистически значимое улучшение нутритивного статуса, показателей ОФВ1, ФЖЕЛ, СОС 25–75, хлоридов пота, уровней панкреатической эластазы, щелочной фосфатазы (ЩФ), гамма-глутамилтранспептидазы (ГГТП); двойной — показателей холестаза (общего билирубина, ЩФ, ГГТП). В группе, не получавшей терапию CFTR-модуляторами, отмечены тенденция к снижению ОФВ1, ФЖЕЛ, прогрессирование внешнесекреторной недостаточности поджелудочной железы, стабильно высокий уровень ЩФ. Использование таргетной терапии статистически значимо снижало потребность в госпитализации при обострении бронхолегочного процесса.

Заключение

Заключение. Применение терапии CFTR-модуляторами снизило риск обострений бронхолегочного процесса, потребовавших госпитализации (ОР = 2,09–11,00). Применение тройной терапии, в сравнении с двойной, показало больший клинический эффект в улучшении нутритивного статуса, функционирования органов дыхания, снижении у всех пациентов и достижении нормальных значений у трети пациентов (35,5 %) хлоридов пота. Применение двойной терапии показало бÓльшую эффективность в снижении показателей холестаза.

Background

Background. Cystic fibrosis (CF) pharmacotherapy aims to restore CFTR protein function. Comparing CFTR modulators’ effectiveness can inform personalized treatment approaches.

The aim of the study is to evaluate the effectiveness of CFTR modulator therapy in children with cystic fibrosis.

Materials and methods

Materials and methods. An open prospective comparative non-randomized study (December 2022 — November 2023) included 81 CF patients aged 2–17 years: 35 received triple therapy (elecsacaftor/tezacaftor/ivacaftor), 23 received double therapy (ivacaftor/lumacaftor), and 23 were controls without CFTR modulators. Evaluations occurred at baseline and after 12 months.

Results

Results. Triple therapy improved nutritional status, lung function (FEV1, FVC, MEF25–75), sweat chloride levels, pancreatic elastase, and liver enzymes (alkaline phosphatase, GGTP); double therapy improved cholestasis markers (OB, alkaline phosphatase, GGTP). Controls showed declining lung function, worsening pancreatic insufficiency, and persistently elevated alkaline phosphatase. Targeted therapy reduced hospitalizations due to bronchopulmonary exacerbations.

Conclusion

Conclusion. CFTR modulator therapy decreased hospitalization risks (HR = 2.09–11.00). Triple therapy had greater benefits than double therapy in improving nutrition, respiratory function, and lowering sweat chlorides (normalizing in 35.5 % of patients). Double therapy effectively reduced cholestasis.

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