Budesonide/formoterol Turbuhaler® as needed in mild asthma: results of SYGMA-1 and SYGMA-2 trials (SYmbicort® Given as needed in Mild Asthma)

According to the modern concepts, asthma is a heterogeneous disease characterized by chronic airway inflammation and respiratory symptoms, which vary in time and intensity and manifest together with variable obstruction of the airways. Asthma is responsible for the deterioration of health status and quality of life in approximately 339 million of adult patients and children worldwide. Despite the fact that asthma is a chronic inflammatory disease, patients with asthma generally inadequately receive anti-inflammatory therapy in real clinical practice and rely on short-acting beta2-agonists (SABA) too much; this can “mimic” worsening of asthma symptoms. SABA monotherapy “on demand” does not affect chronic airway inflammation, underlying asthma occurrence and progression. As a result, such patients still have the risk of asthma exacerbation and disease progression. Therefore, the need of a new therapeutic strategy for patients with milder asthma (steps 1 and 2), which would provide anti-inflammatory treatment considering the low adherence to the regular maintenance therapy and high dependency on SABA, is obvious. Such approach has become available after the SYGMA (SYmbicort® Given as needed in Mild Asthma) trial was completed. According to the results of this trial, budesonide/formoterol 160/4.5 µg/dose as needed was superior to as needed SABA in better asthma control and decrease in severe asthma exacerbation rate by 64% (p < 0.001). Results of SYGMA 1 and 2 trials also demonstrated that budesonide/formoterol 160/4.5 µg/dose as needed was noninferior compared to regular treatment with budesonide in preventing severe asthma exacerbations while the cumulative dose of budesonide was reduced by ≥75%.

1. Russian Respiratory Society. Federal guidelines on diagnosis and treatment of bronchial asthma. 2018. Available at: http://spulmo.ru/obrazovatelnye-resursy/federalnye-klinicheskie-rekomendatsii/ [Accessed: May 15, 2019] (in Russian).

2. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. Updated 2019. Available at: ttps://ginasthma.org/wp-content/uploads/2019/06/GINA-2019-main-report-June-2019-wms.pdf [Accessed: May 20, 2015].

3. O’Byrne P.M., FitzGerald J.M., Bateman E.D. et al. Inhaled combined budesonide-formoterol as needed in mild asthma [article and supplementary appendix]. N. Engl. J. Med. 2018; 378: 1865–1876. DOI: 10.1056/NEJMoa1715274.

4. Bateman E.D., Reddel H.K., O’Byrne P.M. et al. As-needed budesonide-formoterol versus maintenance budesonide in mild asthma [article and supplementary appendix]. N. Engl. J. Med. 2018; 378: 1877–1887. DOI: 10.1056/NEJMoa1715275.

5. Emel'yanov A.V., Leshenkova E.V., Partavi M.S. [Pharmacological therapy of bronchial asthma: state-of-art and future perspectives]. Farmateka 2018; (8): 58–64. DOI: 10.18565/pharmateca.2018.8.58-64 (in Russian).

6. Boulay M.E., Boulet L.P. Discordance between asthma control clinical, physiological and inflammatory parameters in mild asthma. Respir. Med. 2013; 107 (4): 511–518. DOI: 10.1016/j.rmed.2012.12.015.

7. Avdeev S.N., Aisanov Z.R., Belevskiy A.S. et al. [Mild bronchial asthma: the present and the future]. Pul'monologiya. 2018; 28 (1): 84–95. DOI: 10.18093/0869-0189-2018-28-1-84-95 (in Russian).

8. Olaguibel J.M., Quirce S., Juliá B. et al. Measurement of asthma control according to global initiative for Asthma guidelines: a comparison with the Asthma Control Questionnaire. Respir. Res. 2012; 13: 50. DOI: 10.1186/1465-9921-13-50.

9. Price D., Fletcher M., van der Molen T. Asthma control and management in 8,000 European patients: the REcognise Asthma and LInk to Symptoms and Experience (REALISE) survey. NPJ Prim. Care Respir. Med. 2014; 24: 14009. DOI: 10.1038/npjpcrm.2014.9.

10. Bo D., Small M. Disease Burden of mild asthma: Findings from a Cross-Sectional Real-World Survey. Adv. Ther. 2017; 34 (5): 1109–1127. DOI: 10.1007/s12325-017-0520-0.

11. Arkhipov V.V., Grigoryeva E.V., Gavrishina E.V. [Control of bronchial asthma in Russia: results of NIKA multi-center observational study]. Pul'monologiya. 2011; (6): 87–93. DOI: 10.18093/0869-0189-2011-0-6-87-93 (in Russian).

12. Levy M.L., Andrews R., Buckingham R. et al. Why asthma still kills: the National Review of Asthma Deaths (NRAD). Confidential Enquiry report, May 2014. London: Royal College of Physicians, 2014. Available at: https://www.rcplondon.ac.uk/projects/outputs/why-asthma-still-kills

13. O’Byrne P.M., Jenkins C., Bateman E.D. The paradoxes of asthma management: time for a new approach? Eur. Respir. J. 2017; 50 (3): pii: 1701103. DOI: 10.1183/13993003.01103-2017.

14. Reddel H.K., Busse W.W., Pedersen S. et al. Should recommendations about starting inhaled corticosteroid treatment for mild asthma be based on symptom frequency: a post-hoc efficacy analysis of the START study. Lancet. 2017; 389 (10065): 157–166. DOI: 10.1016/S0140-6736(16)31399-X.

15. Bårnes C.B., Ulrik C.S. Asthma and adherence to inhaled corticosteroids: current status and future perspectives. Respir. Care. 2015; 60 (3): 455–468. DOI: 10.4187/respcare.03200.

16. O'Byrne P.M., FitzGerald J.M., Zhong N. et al. The SYGMA programme of phase 3 trials to evaluate the efficacy and safety of budesonide/formoterol given 'as needed' in mild asthma: study protocols for two randomised controlled trials. Trials. 2017; 18 (1): 12. DOI: 10.1186/s13063-016-1731-4.

17. Partridge M.R., van der Molen T., Myrseth S.E., Busse W.W. Attitudes and actions of asthma patients on regular maintenance therapy: the INSPIRE study. BMC Pulm. Med. 2006; 6: 13. DOI: 10.1186/1471-2466-6-13.

18. Tattersfield A.E., Postma D.S., Barnes P.J. et al. Exacerbations of asthma: a descriptive study of 425 severe exacerbations. The FACET International Study Group. Am. J. Respir. Crit. Care Med. 1999; 160 (2): 594–599. DOI: 10.1164/ajrccm.160.2.9811100.

19. Rabe K.F., Vermeire P.A., Soriano J.B., Maier W.C. Clinical management of asthma in 1999: the Asthma Insights and Reality in Europe (AIRE) study. Eur. Respir. J. 2000; 16 (5): 802–807. DOI: 11510801.

20. Schatz M., Zeiger R.S., Vollmer W.M. et al. Validation of β-agonist long-term asthma control scale derived from computerized pharmacy data. J. Allergy Clin. Immunol. 2006; 117 (5): 995–1000. DOI: 10.1016/j.jaci.2006.01.053.

21. Papi A., Canonica G.W., Maestrelli P. et al. Rescue use of beclomethasone and albuterol in a single inhaler for mild asthma. N. Engl. J. Med. 2007; 356 (20): 2040–2052. DOI: 10.1056/NEJMoa063861.