pulmoПульмонологияPULMONOLOGIYA0869-01892541-9617Scientific and Practical Journal “PULMONOLOGIYA” LLC10.18093/0869-0189-2017-27-4-502-514pulmo-900Research ArticleОБЗОРЫREVIEWНовые возможности терапии идиопатического легочного фиброзаNew abilities in therapy of idiopathic pulmonary fibrosisАвдеевС. Н.AvdeevS. N.

д. м. н., член-корр. Российской академии наук, профессор, главный внештатный специалист-пульмонолог Министерства здравоохранения Российской Федерации, руководитель клинического отдела,

105077, Россия, Москва, ул. 11-я Парковая, 32, корп. 4

Doctor of Medicine, Professor, Corresponding Member of Russian Academy of Sciences, Chief Pulmonologist of Healthcare Ministry of Russian Federation, Head of Clinical Division,

ul. Odinnadtsataya Parkovaya 32, build. 4, Moscow, 105077

serg_avdeev@list.ruФедеральное государственное бюджетное учреждение «Научно-исследовательский институт пульмонологии Федерального медико-биологического агентства России»РоссияFederal Pulmonology Research Institute, Federal Medical and Biological Agency of RussiaRussian Federation201716102017274502514Copyright © Авдеев С.Н., 20172017Авдеев С.Н.Avdeev S.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.pulmonology.ru/pulm/article/view/900

Идиопатический легочный фиброз (ИЛФ) является прогрессирующим фиброзирующим заболеванием легких со средней выживаемостью пациентов около 2–3 лет от момента постановки диагноза. Нинтеданиб – ингибитор тирозинкиназы, мишенью которого являются рецепторы факторов роста PDGF, FGF и VEGF. Использование нинтеданиба одобрено для терапии ИЛФ во многих странах на основе результатов исследования II фазы TOMORROW и 2 репликативных исследований III фазы INPULSIS. В исследованиях INPULSIS на фоне терапии нинтеданибом продемонстрировано значительное уменьшение ежегодной скорости снижения форсированной жизненной емкости легких (ФЖЕЛ), а время до 1-го обострения ИЛФ и стабилизация показателей качества жизни по шкале SGRQ положительно изменились в исследовании INPULSIS-2. В совокупном анализе исследований TOMORROW и INPULSIS показано, что при терапии нинтеданибом по сравнению с плацебо снижается летальность пациентов с ИЛФ. В исследовании INPULSIS не выявлено различий по способности нинтеданиба замедлять падение показателя ФЖЕЛ между пациентами с классическим ИЛФ и возможным ИЛФ (т. е. у больных с возможным паттерном ОИП с тракционными бронхоэктазами по данным КТВР без хирургической биопсии легких). В субгрупповых анализах исследования INPULSIS эффективность терапии нинтеданибом подтверждена у всех пациентов с ИЛФ, независимо от возраста, пола, расы, исходных значений ФЖЕЛ, диффузионной способности легких по окиси углерода, наличия эмфиземы, использования антирефлюксной терапии или системных глюкокортикостероидов. В исследовании INPULSIS частота тяжелых нежелательных явлений (НЯ) между группами нинтеданиба и плацебо значительно не различалась. Диарея была наиболее частым НЯ при терапии нинтеданибом, частота ее развития составила около 60 %, но в большинстве случаев – легкой или средней тяжести, отмены препарата не требовалось. Необходимо проведение дальнейших исследований по изучению эффективности нинтеданиба у больных ИЛФ с более широкими критериями включения, другими фибротическими интерстициальными заболеваниями легких, а также изучение эффективности и безопасности комбинации нинтеданиба и пирфенидона. Стратегия терапия больных ИЛФ в идеале должна быть основана на индивидуальных характеристиках каждого больного.

Idiopathic pulmonary fibrosis (IPF) is progressive fibrosing lung disease with average survival of 2 to 3 years after the diagnosis. Nintedanib is tyro sine kinase inhibitor targeted to receptors of PDGF, FGF and VEGF growth factors. Use of nintedanib in IPF was approved in many countries on the basis of results of TOMORROW phase 2 clinical trial and two phase 3 INPULSIS replicate studies. Significant reduction in the annual FVC decline was shown under the therapy with nintedanib in the INPULSIS studies. Improvement in time to the first exacerbation and stabilization of quality of life measured by SGRQ scale were obtained in the INPULSIS1 study. In pooled analysis of TOMORROW and INPULSIS study results, nintedanib decreased mortality in IPF patients compared to placebo. FVC decline was not differed between patients with typical and possible IPF (i.e., patients with traction bronchiectasis in HRCT, but without surgical lung biopsy) in the INPULSIS trials. In subgroup analysis in INPULSIS trials, the efficacy of nintedanib was confirmed in all IPF patients independently on age, gender, race, baseline FVC and DLCO, presence of emphy sema, use of antireflux therapy or systemic steroids. Frequency of severe adverse events (AE) did not differed between groups of nintedanib and placebo in the INPULSIS trials. The most frequent AE was diarrhea (60%), mostly mild or moderate, which did not require withdrawal the treat ment. Further investigations are needed to study efficacy of nintedanib in IPF patients with more extended inclusion criteria and other fibrosing interstitial lung diseases, as well as efficacy and safety of combinations of nintedanib and pirfenidone. Ideally, the therapeutic strategy in IPF patients should be individualized according to characteristics of the patient.

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