Ulyanovsk Medico-biological Journal

Клиническая медицина

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DOI: 10.23648/UMBJ.2017.28.8738

УДК 615.032

 

ВЗГЛЯД КЛИНИЧЕСКОГО ФАРМАКОЛОГА НА ВЫБОР ФИКСИРОВАННОЙ КОМБИНАЦИИ БУДЕСОНИДА И ФОРМОТЕРОЛА ДЛЯ ЛЕЧЕНИЯ БОЛЬНЫХ БРОНХИАЛЬНОЙ АСТМОЙ И ХРОНИЧЕСКОЙ ОБСТРУКТИВНОЙ БОЛЕЗНЬЮ ЛЕГКИХ

 

В.А. Серов, М.Ю. Кузовенкова, Д.В. Серова

ФГБОУ ВО «Ульяновский государственный университет», г. Ульяновск, Россия

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В последние годы стремительно растет распространенность бронхиальной астмы (БА) и хронической обструктивной болезни легких (ХОБЛ). В обзоре с позиции клинического фармаколога представлен сравнительный анализ клинического применения и фармакоэкономической эффективности различных представителей фиксированной комбинации ингаляционного глюкокортикостероида будесонида и селективного β2-агониста длительного действия формотерола. Современные международные рекомендации по диагностике и лечению БА (GINA, 2016) и ХОБЛ (GOLD, 2016) предусматривают расширение показаний к использованию данной комбинации лекарственных средств.

Большое количество дженериков затрудняет выбор практическими врачами конкретного лекарственного средства. Критериями предпочтений при назначении лекарственных средств являются, наряду с клинической, клинико-экономическая эффективность и удобство применения
в реальной клинической практике. В обзоре представлены сравнительные клинико-экономические характеристики, особенности применения, а также доказательная база для применения фиксированной комбинации будесонида и формотерола.

Малое количество небольших по объему имеющихся исследований, сравнивающих клиническую эффективность различных дженериков, не позволяет сделать окончательных выводов по их применению. Авторами работы показано, что лекарственные средства, наиболее эффективные
с экономической точки зрения, как правило, имеют небольшую доказательную базу, часто обладают определенными недостатками в применении (сложность использования, особенно для пожилых людей и детей, ограничения в температурном режиме при хранении медикаментов). Поиск информации о проведении клинических испытаний и стоимости терапии различными дженериками осуществлен по базам данных ClinicalTrials.gov, PubMed и grls.rosminzdrav.ru. Представленная информация позволяет понять основные отличия зарегистрированных в России фиксированных комбинаций будесонида и формотерола, что является необходимым для принятия рационального решения по лечению больных БА и ХОБЛ, выбора наиболее приемлемых дженериков для определенных категорий больных.

Ключевые слова: лечение бронхиальной астмы, лечение хронической обструктивной болезни легких, фиксированная комбинация будесонида и формотерола, фармакоэкономическая эффективность.

 

Литература

  1. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention Online Appendix 2015 update. Available at: http://www.ginasthma.сom (дата обращения: 18.01.2017).
  2. Федеральная целевая программа «Бронхиальная астма» (2011–2015 гг.). Available at: www.pulmonology.ru/publications/files/FCP-bronhialqnaq_astma.doc (дата обращения: 18.01.2017).
  3. Chuchalin A.G., Khaltaev N., Antonov N.S., Galkin D.V., Manakov L.G., Antonini P., Murphy M., Solodovnikov A.G., Bousquet J., Pereira M.H., Demko I.V. Chronic respiratory diseases and risk factors in 12 regions of the Russian Federation.Int. J. Chron. Obstruct. Pulmon. Dis. 2014; 9: 963–974.
  4. Global Initiative for Chronic Obstructive Lung Disease (GOLD) Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. (дата обращения: 18.01.2017).
  5. Aalbers R., Vogelmeier C., Kuna P.Achieving asthma control with ICS/LABA: A review of strategies for asthma management and Respir. Med. 2016; 111: 1–7.
  6. Kardos P. Budesonide/formoterol maintenance and reliever therapy versus free-combination therapy for asthma: a real-life study. Pneumologie. 2013; 67 (8): 463–470.
  7. Buhl R., Kuna P., Peters M.J., Andersson T.L., Naya I.P., Peterson S., Rabe K.F. The effect of budesonide/formoterol maintenance and reliever therapy on the risk of severe asthma exacerbations following episodes of high reliever use: an exploratory analysis of two randomised, controlled studies with comparisons to standard therapy. Respir. Res. 2012; 13: 59.
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  9. Lee S.D., Xie C.M., Yunus F., Itoh Y., Ling X., Yu W.C., Kiatboonsri S. Efficacy and tolerability of budesonide/formoterol added to tiotropium compared with tiotropium alone in patients with severe or very severe COPD: A randomized, multicentre study in East Asia. Respirology. 2016; 21 (1): 119–127.
  10. Bayiz H., Ozkaya S., Dirican A., Ece F. The rapid effects of budesonide plus formoterol in patients with obstructive airway diseases. Drug Des. Devel. Ther. 2015; 9: 5287–5590.
  11. Takeyama K., Kondo M., Tagaya E., Kirishi S., Ishii M., Ochiai K., Isono K., Tamaoki J.Budesonide/formoterol maintenance and reliever therapy in moderate-to-severe asthma: effects on eosinophilic airway inflammation. Allergy Asthma Proc. 2014; 35 (2): 141–147.
  12. Lin C.H., Hsu J.Y., Hsiao Y.H., Tseng C.M., Su V.Y., Chen Y.H., Yang S.N., Lee Y.C., Su K.C., Perng D.W. Budesonide/formoterol maintenance and reliever therapy in asthma control: Acute, dose-related effects and real-life effectiveness. Respirology. 2015; 20 (2): 264–272.
  13. Авдеев С.Н., Айсанов З.Р., Архипов В.В., Белевский А.С., Игнатова Г.Л., Ильина Н.И., Емельянов А.В., Княжеская Н.П., Курбачева О.М., Лещенко И.В., Ненашева Н.М., Фассахов Р.С. Согласованные рекомендации по применению режима единого ингалятора фиксированной комбинации будесонид/формотерол (SMART) в терапии пациентов с бронхиальной астмой. Практическая пульмонология. 2016; 1: 2–15.
  14. Scicchitano R., Aalbers R., Ukena D., Manjra A., Fouquert L., Centanni S., Boulet L.P., Naya I.P., Hultquist C. Efficacy and safety of Budesonide/Formoterol a single inhaler therapy versus a higher dose of budesonide in moderate to severe asthma. Curr. Med. Res. Opin. 2004; 20 (9): 1403–1418.
  15. O'Byrne P.M., Bisgaard H., Godard P.P., Pistolesi M., Palmqvist M., Zhu Y., Ekström T., Bateman E.D.Budesonide/formoterol combination therapy as both maintenance and reliever medication in asthma. Am. J. Respir. Crit. Care Med. 2005; 171 (2): 129–136.
  16. Rabe K.F., Pizzichini E., Ställberg B., Romero S., Balanzat A.M., Atienza T., Lier P.A., Jorup C.Budesonide/formoterol in a single inhaler for maintance and reliever therapy in mild-moderate asthma. Chest. 2006; 129: 246–256.
  17. Rabe K.F., Atienza T., Magyar P., Larsson P., Jorup C., Lalloo U.G. Effect of budesonide in combinatio with formoterol for reliever therapy in asthma exacerbations: a randomised controlled, double-blind study. Lancet. 2006; 368: 744–753.
  18. Bousquet J., Boulet L.P., Peters M.J., Magnussen H., Quiralte J., Martinez-Aquilar N.E., Carlsheimer A. Budesonide/formoterol for maintenance and relief in uncontrolled asthma vs. high-dose salmeterol/fluticasone. Respir. Med. 2007; 101 (12): 2437–2446.
  19. Pichler J., Patel M., Reddel H. Effect of smoking status on the efficacy of the SMART regimen in high risk asthma. Respirology. 2016; 21 (5): 858–866.
  20. Ställberg B., Naya I., Ekelund J., Eckerwall G. Real-life use of budesonide/formoterol in clinical practice: a 12-month follow-up assessment in a multi-national study of asthma patients established on single-inhaler maintenance and reliever therapy. Int. J. Clin. Pharmacol Ther. 2015; 53 (6): 447–455.
  21. Peters S.P., Bleecker E.R., Canonica G.W., Park Y.B., Ramirez R., Hollis S., Fjallbrant H., Jorup C., Martin U.J. Serious Asthma Events with Budesonide plus Formoterol vs. Budesonide Alone. N. Engl. J. Med. 2016; 375 (9): 850–860.
  22. Lin J., Tang Y., Xiu Q., Kang J., Cai S., Huang K., Itoh Y., Ling X., Zhong N. Real-life effectiveness of budesonide/formoterol therapy in asthma: A subanalysis of the SMARTASIA study. Allergy Asthma Proc. 2016; 37 (1): 27–34.
  23. Vogelmeier C., Naya I., Ekelund J.Budesonide/formoterol maintenance and reliever therapy in Asian patients (aged ≥16 years) with asthma: a sub-analysis of the COSMOS study. Clin. Drug Investig. 2012; 32 (7): 439–449.
  24. Saito T., Hasunuma T. Safety and Tolerability of High-Dose Budesonide/Formoterol via Turbuhaler® in Japanese Patients with Asthma: A Randomized, Double-Blind, Crossover, Active Comparator-Controlled, Phase III Study. Clin. Drug Investig. 2012; 32 (1): 51–61.
  25. Imad H., Yasir G. Epidemiological and clinical characteristics, spirometric parameters and response to budesonide/formoterol in patients attending an asthma clinic: an experience in a developing country. Pan. Afr. Med. J. 2015; 21: 154.
  26. Boonsawat W., Thinkhamrop B. Role of budesonide/formoterol maintenance and reliever therapy: a pragmatic study. Asian Pac. J. Allergy Immunol. 2014; 32 (2): 160–165.
  27. Kagohashi K., Satoh H., Ohara G., Miyazaki K., Kawaguchi M., Kurishima K., Hizawa N. Long-term safety of budesonide/formoterol for the treatment of elderly patients with bronchial asthma. Exp. Ther. Med. 2014; 7 (4): 1005–1009.
  28. Цой А.Н., Архипов В.В., Чапурин С.А., Чурилин Ю.Ю. Фармакоэкономическое исследование новой концепции применения Симбикорта у больных бронхиальной астмой. Пульмонология. 2007; 3: 34–40.
  29. Воробьев П.А., Белевский А.С., Авксентьева М.В., Смирнова М.С., Максимова Л.В., Сура М.В. Клинико-экономическое исследование целесообразности применения препарата Симбикорт Турбухалер для лечения бронхиальной астмы. Пульмонология. 2007; 1: 54–59.
  30. Virchow J.C., Rodriguez-Roisin R., Papi A., Shah T.P., Gopalan G. A randomized, double-blinded, double-dummy efficacy and safety study of budesonide-formoterol Spiromax® compared to budesonide-formoterol Turbuhaler® in adults and adolescents with persistent asthma. BMC Pulm. Med. 2016; 16: 42.
  31. Thorsson L., Edsbacker S. Less variability in lung deposition of budesonide via Turbuhaler® than of fluticasone via Discus®/Accuhaler® and pMDI in adults. AJRCCM. 2003; 167 (7): A896.
  32. Zervas E., Samitas K., Gaga M. Assessment of satisfaction with different dry powder inhalation devices in Greek patients with COPD and asthma: the ANASA study. Int. J. Chron. Obstruct. Pulmon. Dis. 2016; 11: 1845–1855.

 

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DOI: 10.23648/UMBJ.2017.28.8738

CLINICAL PHARMACOLOGIST ON BUDESONIDE/FORMOTEROL FIXED DOSE COMBINATION FOR TREATING PATIENTS WITH BRONCHIAL ASTHMA AND CHRONIC OBSTRUCTIVE LUNG DISEASE

 

V.A. Serov, M.Yu. Kuzovenkova, D.V. Serova

Ulyanovsk State University, Ulyanovsk, Russia

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In recent years, the incidence rate of bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) is increasing. This review presents a comparative analysis of clinical administration and cost-effectiveness of a fixed combination of inhaled glucocorticosteroid, budesonide, and selective long-acting beta2-agonist, formoterol. Clinical pharmacologists try to express their point of view on the abovementioned problem. Global Initiative for Asthma (GINA, 2016) and Global Initiative for Chronic Obstruction Lung Disease (GOLD, 2016) provide for a wider indication of this combination of drugs.

It is difficult for practitioners to choose a particular drug because of a large number of generics. Criteria of preferences in prescribing such drugs are clinical efficacy, cost-effectiveness, and ease of usability in real clinical practice. The review presents comparative clinical and cost performance, administration details, as well as the evidence base for using budesonide/formoterol fixed combination.

The number of available small-scale studies, comparing the clinical performance of various generics, does not allow us to draw definitive conclusions on their use. The authors of the paper prove that the most cost-effective pharmacologic agents, as a rule, have a small evidence base, often have certain disadvantages in administration (complexity of use, especially for the elderly patients and children, and storing temperature restrictions). The search for information on existing clinical trials and the cost-effectiveness of various generics was carried out using ClinicalTrials.gov, PubMed and grls.rosminzdrav.ru databases. The given data make it possible to understand the main differences between budesonide/formoterol combinations registered in Russia. This information can help to make rational decisions while treating patients with BA and COPD, and choosing the most suitable generics for certain groups of patients.

Keywords: asthma management, COPD management, budesonide/formoterol fixed combination, cost-effectiveness.

 

References

1.    Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention Online Appendix 2015 update. Available at: http://www.ginasthma.som (accessed: 18.01.2017).

2.    Federal'naya tselevaya programma «Bronkhial'naya astma» (2011–2015 gody) [Federal Target Programme “Bronchial asthma” (2011–2015)]. Moscow; 2009. Available at: http://www.pulmonology.ru/ publications/files/FCP-bronhialqnaq_astma.doc (accessed:18.01.2017) (in Russian).

3.    Chuchalin A.G., Khaltaev N., Antonov N.S., Galkin D.V., Manakov L.G., Antonini P., Murphy M., Solodovnikov A.G., Bousquet J., Pereira M.H., Demko I.V. Chronic respiratory diseases and risk factors in 12 regions of the Russian Federation. Int. J. Chron. Obstruct. Pulmon. Dis. 2014; 9: 963–974.

4.    Global Initiative for Chronic Obstructive Lung Disease (GOLD) Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. 2017. Available at: http://www.goldcopd.org (accessed: 18.01.2017).

5.    Aalbers R., Vogelmeier C., Kuna P. Achieving asthma control with ICS/LABA: A review of strategies for asthma management and prevention. Respir. Med. 2016; 111: 1–7.

6.    Kardos P. Budesonide/formoterol maintenance and reliever therapy versus free-combination therapy for asthma: a real-life study. Pneumologie. 2013; 67 (8): 463–470.

7.    Buhl R., Kuna P., Peters M.J., Andersson T.L., Naya I.P., Peterson S., Rabe K.F. The effect of budesonide/formoterol maintenance and reliever therapy on the risk of severe asthma exacerbations following episodes of high reliever use: an exploratory analysis of two randomised, controlled studies with comparisons to standard therapy. Respir. Res. 2012; 13: 59.

8.    Shmelev E.I., Zhestkov A.V., Vizel' A.A., Zagidullin Sh.Z., Karoli N.A., Mishlanov V.Yu., Fassakhov R.S., Khamitov R.F., Vavashkina E.A., Vizel' I.Yu., Vorob'eva N.B., Kulbaisov A.M., Kostina E.M., Kunyaeva T.A., Pavlov P.I., Peskov A.B., Postnikova L.B., Starodubtseva O.I., Sushentsov V.G., Farkhutdinov U.R. Optimizatsiya lecheniya khronicheskoy obstruktivnoy bolezni legkikh: put' k dvoynoy bronkhodilatatsii (zaklyuchenie soveta ekspertov Privolzhskogo federal'nogo okruga Rossii) [Optimization of chronic obstructive pulmonary disease treatment: the way to double bronchodilation (Report of the Expert Council of the Volga Federal District of Russia)]. Vestnik sovremennoy klinicheskoy meditsiny. 2016; 9 (3): 82–89 (in Russian).

9.    Lee S.D., Xie C.M., Yunus F., Itoh Y., Ling X., Yu W.C., Kiatboonsri S. Efficacy and tolerability of budesonide/formoterol added to tiotropium compared with tiotropium alone in patients with severe or very severe COPD: A randomized, multicentre study in East Asia. Respirology. 2016; 21 (1): 119–127.

10. Bayiz H., Ozkaya S., Dirican A., Ece F. The rapid effects of budesonide plus formoterol in patients with obstructive airway diseases. Drug Des. Devel. Ther. 2015; 9: 5287–5290.

11. Takeyama K., Kondo M., Tagaya E., Kirishi S., Ishii M., Ochiai K., Isono K., Tamaoki J. Budesonide/formoterol maintenance and reliever therapy in moderate-to-severe asthma: effects on eosinophilic airway inflammation. Allergy Asthma Proc. 2014; 35 (2): 141–147.

12. Lin C.H., Hsu J.Y., Hsiao Y.H., Tseng C.M., Su V.Y., Chen Y.H., Yang S.N., Lee Y.C., Su K.C., Perng D.W. Budesonide/formoterol maintenance and reliever therapy in asthma control: Acute, dose-related effects and real-life effectiveness. Respirology. 2015; 20 (2): 264–272.

13. Avdeev S.N., Aysanov Z.R., Arkhipov V.V., Belevskiy A.S., Ignatova G.L., Il'ina N.I., Emel'yanov A.V., Knyazheskaya N.P., Kurbacheva O.M., Leshchenko I.V., Nenasheva N.M., Fassakhov R.S. Soglasovannye rekomendatsii po primeneniyu rezhima edinogo ingalyatora fiksirovannoy kombinatsii budesonid/formoterol (SMART) v terapii patsientov s bronkhial'noy astmoy [Concerted recommendations for the use of common inhalers for budesonide/formoterol fixed combination inhaler (SMART) while treating patients with bronchial asthma]. Prakticheskaya pul'monologiya. 2016; 1: 2–15
(in Russian).

14. Scicchitano R., Aalbers R., Ukena D., Manjra A., Fouquert L., Centanni S., Boulet L.P., Naya I.P., Hultquist C. Efficacy and safety of Budesonide/Formoterol a single inhaler therapy versus a higher dose of budesonide in moderate to severe asthma. Curr. Med. Res. Opin. 2004; 20 (9): 1403–1418.

15. O'Byrne P.M., Bisgaard H., Godard P.P., Pistolesi M., Palmqvist M., Zhu Y., Ekström T., Bateman E.D. Budesonide/formoterol combination therapy as both maintenance and reliever medication in asthma. Am. J. Respir. Crit. Care Med. 2005; 171 (2): 129–136.

16. Rabe K.F., Pizzichini E., Ställberg B., Romero S., Balanzat A.M., Atienza T., Lier P.A., Jorup C. Budesonide/formoterol in a single inhaler for maintance and reliever therapy in mild-moderate asthma. Chest. 2006; 129: 246–256.

17. Rabe K.F., Atienza T., Magyar P., Larsson P., Jorup C., Lalloo U.G. Effect of budesonide in combinatio with formoterol for reliever therapy in asthma exacerbations: a randomised controlled, double-blind study. Lancet. 2006; 368: 744–753.

18. Bousquet J., Boulet L.P., Peters M.J., Magnussen H., Quiralte J., Martinez-Aquilar N.E., Carlsheimer A. Budesonide/formoterol for maintenance and relief in uncontrolled asthma vs. high-dose salmeterol/fluticasone. Respir. Med. 2007; 101 (12): 2437–2446.

19. Pichler J., Patel M., Reddel H. Effect of smoking status on the efficacy of the SMART regimen in high risk asthma. Respirology. 2016; 21 (5): 858–866.

20. Ställberg B., Naya I., Ekelund J., Eckerwall G. Real-life use of budesonide/formoterol in clinical practice: a 12-month follow-up assessment in a multi-national study of asthma patients established on single-inhaler maintenance and reliever therapy. Int. J. Clin. Pharmacol. Ther. 2015; 53 (6): 447–455.

21. Peters S.P., Bleecker E.R., Canonica G.W., Park Y.B., Ramirez R., Hollis S., Fjallbrant H., Jorup C., Martin U.J. Serious Asthma Events with Budesonide plus Formoterol vs. Budesonide Alone. N. Engl. J. Med. 2016; 375 (9): 850–860.

22. Lin J., Tang Y., Xiu Q., Kang J., Cai S., Huang K., Itoh Y., Ling X., Zhong N. Real-life effectiveness of budesonide/formoterol therapy in asthma: A subanalysis of the SMARTASIA study. Allergy Asthma Proc. 2016; 37 (1): 27–34.

23. Vogelmeier C., Naya I., Ekelund J. Budesonide/formoterol maintenance and reliever therapy in Asian patients (aged ≥16 years) with asthma: a sub-analysis of the COSMOS study. Clin. Drug Investig. 2012; 32 (7): 439–449.

24. Saito T., Hasunuma T. Safety and Tolerability of High-Dose Budesonide/Formoterol via Turbuhaler® in Japanese Patients with Asthma : A Randomized, Double-Blind, Crossover, Active Comparator-Controlled, Phase III Study. Clin. Drug Investig. 2012; 32 (1): 51–61.

25. Imad H., Yasir G. Epidemiological and clinical characteristics, spirometric parameters and response to budesonide/formoterol in patients attending an asthma clinic: an experience in a developing country. Pan. Afr. Med. J. 2015; 21: 154.

26. Boonsawat W., Thinkhamrop B. Role of budesonide/formoterol maintenance and reliever therapy: a pragmatic study. Asian Pac. J. Allergy Immunol. 2014; 32 (2): 160–165.

27. Kagohashi K., Satoh H., Ohara G., Miyazaki K., Kawaguchi M., Kurishima K., Hizawa N. Long-term safety of budesonide/formoterol for the treatment of elderly patients with bronchial asthma. Exp. Ther. Med. 2014; 7 (4): 1005–1009.

28. Tsoy A.N., Arkhipov V.V., Chapurin S.A., Churilin Yu.Yu. Farmakoekonomicheskoe issledovanie novoy kontseptsii primeneniya Simbikorta u bol'nykh bronkhial'noy astmoy [Pharmacoeconomic trial on novelty of Symbicort administration in patients with bronchial asthma]. Pul'monologiya. 2007; 3: 34–40 (in Russian).

29. Vorob'ev P.A., Belevskiy A.S., Avksent'eva M.V., Smirnova M.S., Maksimova L.V., Sura M.V. Kliniko-ekonomicheskoe issledovanie tselesoobraznosti primeneniya preparata Simbikort Turbukhaler dlya lecheniya bronkhial'noy astmy [Clinical and cost-effective performance of Symbicort Turbuhaler administration while treating patients with bronchial asthma]. Pul'monologiya. 2007; 1: 54–59 (in Russian).

30. Virchow J.C., Rodriguez-Roisin R., Papi A., Shah T.P., Gopalan G. A randomized, double-blinded, double-dummy efficacy and safety study of budesonide-formoterol Spiromax® compared to budesonide-formoterol Turbuhaler® in adults and adolescents with persistent asthma. BMC Pulm. Med. 2016; 16: 42.

31. Thorsson L., Edsbacker S. Less variability in lung deposition of budesonide via Turbuhaler® than of fluticasone via Discus®/Accuhaler® and pMDI in adults. AJRCCM. 2003; 167 (7 Suppl): A 896.

32. Zervas E., Samitas K., Gaga M. Assessment of satisfaction with different dry powder inhalation devices in Greek patients with COPD and asthma: the ANASA study. Int. J. Chron. Obstruct. Pulmon. Dis. 2016; 11: 1845–1855.