Preview

Meditsinskiy sovet = Medical Council

Advanced search

Clinical efficacy of mepolizumab in the treatment of severe eosinophilic asthma in children

https://doi.org/10.21518/2079-701X-2020-18-115-121

Abstract

Severe bronchial asthma in children remains a serious problem, which is caused by high mortality, side effects from therapy with high doses of glucocorticosteroids and a significant consumption of health resources. According to statistics from the Monitoring, Analysis and Strategic Health Development Department of the Ministry of Health of the Russian Federation, 1028.6 BA cases per 100,000 children under 14 years of age were registered in Russia in 2017. The article presents modern data on the pathogenesis of bronchial asthma, causes of therapy-resistant asthma, participation of interleukin-5 (IL-5) in the development of eosinophilic inflammation. Research data demonstrate the safety and effectiveness of anti-IL-5 therapy as a supplement to standard treatment for severe eosinophilic bronchial asthma and its poor control. Mepolizumab is the most widely researched anti-IL-5-monoclonal drug. It statistically significantly reduces the level of eosinophils in sputum, reduces the frequency of  exacerbations and hospitalizations helps reduce maintenance therapy with glucocorticosteroids. As a result of randomized, placebo-controlled trials mepolizumab has been shown effective and safe in children 6 years of age and older, experts of leading world organizations approved its use for the treatment of severe eosinophilic asthma in children, what makes this drug the only one currently approved for use in patients in this age profile. However, further studies are needed to determine the optimal duration and long-term therapeutic efficacy in children.

About the Authors

V. N. Drozdov
Federal State Autonomous Educational Institution of Higher Education “Sechenov First Moscow State Medical University” of the Ministry of Health of the Russian Federation (Sechenov University)
Russian Federation

Dr. of Sci. (Med.), Professor of the Department of Clinical Pharmacology and Propaedeutics of Internal Diseases

8, Bldg. 2, Trubetskaya St., Moscow, 119991, Russia



A. A. Astapovskiy
Federal State Autonomous Educational Institution of Higher Education “Sechenov First Moscow State Medical University” of the Ministry of Health of the Russian Federation (Sechenov University)
Russian Federation

Clinical resident of the Department of Clinical Pharmacology and Propaedeutics of Internal Diseases

8, Bldg. 2, Trubetskaya St., Moscow, 119991, Russia



S. Yu. Serebrova
Federal State Budgetary Institution “Scientific Centre for Expert Evaluation of Medicinal Products”; Federal State Autonomous Educational Institution of Higher Education “Sechenov First Moscow State Medical University” of the Ministry of Health of the Russian Federation (Sechenov University)
Russian Federation

Dr. of Sci. (Med.), Chief Researcher of Clinical Pharmacology Centre; Professor of the Department of Clinical Pharmacology and Propaedeutics of Internal Diseases

8, Bldg. 2, Petrovsky Boulevard, Moscow, 127051, Russia

8, Bldg. 2, Trubetskaya St., Moscow, 119991, Russia



E. V. Shikh
Federal State Autonomous Educational Institution of Higher Education “Sechenov First Moscow State Medical University” of the Ministry of Health of the Russian Federation (Sechenov University)
Russian Federation

Dr. of Sci. (Med.), Chair of the Department of Clinical Pharmacology and Propaedeutics of Internal Diseases

8, Bldg. 2, Trubetskaya St., Moscow, 119991, Russia



I. A. Komissarenko
Federal State Budgetary Educational Institution of the Higher Education “Yevdokimov Moscow State University of Medicine and Dentistry” of the Ministry of Healthcare of the Russian Federation
Russian Federation

Dr. of Sci. (Med.), Professor of the Department of Polyclinic Therapy

20, Bldg. 1, Delegateskaya St., Moscow, 127473, Russia



References

1. Vos T., Flaxman A.D., Naghavi M., Lozano R., Michaud C., Ezzati M. et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2163–2196. doi: 10.1016/S0140-6736(12)61729-2.

2. Chuchalin A., Khaltaev N., Antonov N., Galkin D., Manakov L., Antonini P. et al. Chronic respiratory diseases and risk factors in 12 regions of the Russian Federation. Int J Chron Obstruct Pulmon Dis. 2014;9(1):963–974. doi: 10.2147/copd.s67283.

3. Avdeev S.N., Nenasheva N.M., Zhudenkov K.V., Petrakovskaya V.A., Izyumova G.V. Prevalence, morbidity, phenotypes and other characteristics of severe bronchial asthma in Russian Federation. Pulmonologiya = Russian Pulmonology Journal. 2018;28(3):341–358. (In Russ.) doi: 10.18093/0869-0189-2018-28-3-341-358.

4. https://minzdrav.gov.ru/ministry/61/22/stranitsa-979/statisticheskie-i-informatsionnye-materialy/statisticheskiy-sbornik-2017-god.

5. Moore W.С., Meyers D.A., Wenzel S.E., Teague W.G., Li H., Li X. et al. Identification of Asthma Phenotypes Using Cluster Analysis in the Severe Asthma Research Program. Am J Respir Critic Care Med. 2010;181(4):315–323. doi: 10.1164/rccm.200906-0896oc.

6. Chung K.F. Asthma phenotyping: a necessity for improved therapeutic precision and new targeted therapies. J Int Med. 2015;279(2):192–204. doi: 10.1111/joim.12382.

7. Fitzpatrick A.M., Jackson D.J., Mauger D.T., Boehmer S.J., Phipatanakul W., Sheehan W.J. et al. Individualized therapy for persistent asthma in young children. J Allergy Clin Immunol. 2016;138(6):1608–1618.e12. doi: 10.1016/j.jaci.2016.09.028.

8. Guilbert T.W., Bacharier L.B., Fitzpatrick A.M. Severe Asthma in Children. J Allergy Clin Immunol Pract. 2014;2(5):489–500. doi: 10.1016/j.jaip.2014.06.022.

9. Chung K.F., Wenzel S.E., Brozek J.L., Bush A., Castro M., Sterk P.J. et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2013;43(2):343–373. doi: 10.1183/09031936.00202013.

10. Vottero A., Kino T., Combe H., Lecomte P., Chrousos G.P. A Novel, C-Terminal Dominant Negative Mutation of the GR Causes Familial Glucocorticoid Resistance through Abnormal Interactions with p160 Steroid Receptor Coactivators. J Clin Endocrinol Metab. 2002;87(6):2658–2667. doi: 10.1210/jcem.87.6.8520.

11. Israel E., Drazen J.M., Liggett S.B., Boushey H.A., Cherniack R.M., Chinchilli V.M. et al. Effect of Polymorphism of the β(2)-Adrenergic Receptor on Response to Regular Use of Albuterol in Asthma. Int Arch Allergy Immunol. 2001;124(1–3):183–186. doi: 10.1159/000053705.

12. Barnes P.J. Corticosteroid resistance in patients with asthma and chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2013;131(3):636–645. doi: 10.1016/j.jaci.2012.12.1564.

13. Gagliardo R., Chanez P., Vignola A.M., Bousquet J., Vachier I., Godard P. et al. Glucocorticoid Receptor α and β in Glucocorticoid Dependent Asthma. Am J Respir Crit Care Med. 2000;162(1):7–13. doi: 10.1164/ajrccm.162.1.9911032.

14. Gupta A., Sjoukes A., Richards D., Banya W., Hawrylowicz C., Bush A., Saglani S. Relationship between Serum Vitamin D, Disease Severity, and Airway Remodeling in Children with Asthma. Am J Respir Crit Care Med. 2011;184(12):1342–1349. doi: 10.1164/rccm.201107-1239oc.

15. Saglani S., Lloyd C.M. Novel concepts in airway inflammation and remodelling in asthma. Eur Respir J. 2015;46(6):1796–1804. doi: 10.1183/13993003.01196-2014.

16. Bossley C.J., Fleming L., Ullmann N., Gupta A., Adams A., Nagakumar P. et al. Assessment of corticosteroid response in pediatric patients with severe asthma by using a multidomain approach. J Allergy Clin Immunol. 2016;138(2):413–420.e6. doi: 10.1016/j.jaci.2015.12.1347.

17. Hossny E., Rosario N., Lee B.W., Singh M., El-Ghoneimy D., Soh J., Le Souef P. The use of inhaled corticosteroids in pediatric asthma: update. World Allergy Organ J. 2016;9:26. doi: 10.1186/s40413-016-0117-0.

18. Milburn M., Hassell A.M., Lambert M.H., Jordan S.R., Proudfoot A.E., Graber P., Wells T.N. A novel dimer configuration revealed by the crystal structure at 2.4 A resolution of human interleukin-5. Nature. 1993;363(6425):172–176. doi: 10.1038/363172a0.

19. Kouro T., Takatsu K. IL-5- and eosinophil-mediated inflammation: from discovery to therapy. Int Immunol. 2009;21(12):1303–1309. doi: 10.1093/intimm/dxp102.

20. Dent L.A., Strath M., Mellor A.L., Sanderson C.J. Eosinophilia in transgenic mice expressing interleukin 5. J Exp Med. 1990;172(5):1425–1431. doi: 10.1084/jem.172.5.1425.

21. Azzawi M., Bradley B., Jeffery P.K., Frew A.J., Wardlaw A.J., Knowles G. et al. Identification of Activated T Lymphocytes and Eosinophils in Bronchial Biopsies in Stable Atopic Asthma. Am Rev Respir Dis. 1990;142(6 Pt 1): 1407–1413. doi: 10.1164/ajrccm/142.6_pt_1.1407.

22. Foster P.S., Hogan S.P., Ramsay A.J., Matthaei K.I., Young I.G. Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model. J Exp Med. 1996;183(1):195–201. doi: 10.1084/jem.183.1.195.

23. Leckie M.J., ten Brinke A., Khan J., Diamant Z., O’Connor B.J., Walls C.M. et al. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet. 2000;356(9248):2144–2148. doi: 10.1016/s0140-6736(00)03496-6.

24. Flood-Page P., Swenson C., Faiferman I., Matthews J., Williams M., Brannick L. et al. A Study to Evaluate Safety and Efficacy of Mepolizumab in Patients with Moderate Persistent Asthma. Am J Respir Crit Care Med. 2007;176(11):1062–1071. doi: 10.1164/rccm.200701-085oc.

25. Powell C., Milan S.J., Dwan K., Bax L., Walters N. Mepolizumab versus placebo for asthma. Cochrane Database Syst Rev. 2015; (7):CD010834. doi: 10.1002/14651858.cd010834.pub2.

26. Haldar P., Brightling C.E., Hargadon B., Gupta S., Monteiro W., Sousa A. et al. Mepolizumab and Exacerbations of Refractory Eosinophilic Asthma. N Engl J Med. 2009;360(10):973–984. doi: 10.1056/nejmoa0808991.

27. Nair P., Pizzichini M.M., Kjarsgaard M., Inman M.D., Efthimiadis A., Pizzichini E. et al. Mepolizumab for Prednisone-Dependent Asthma with Sputum Eosinophilia. N Engl J Med. 2009;360(10):985–993. doi: 10.1056/nejmoa0805435.

28. Pavord I., Korn S., Howarth P., Bleecker E.R., Buhl R., Keene O.N. et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet. 2012;380(9842):651–659. doi: 10.1016/s0140-6736(12)60988-x.

29. Bel E.H., Wenzel S.E., Thompson P.J., Prazma C.M., Keene O.N., Yancey S.W. et al. Oral Glucocorticoid-Sparing Effect of Mepolizumab in Eosinophilic Asthma. N Engl J Med. 2014;371(13):1189–1197. doi: 10.1056/nejmoa1403291.

30. Ortega H.G., Liu M.C., Pavord I.D., Brusselle G.G., FitzGerald J.M., Chetta A. et al. Mepolizumab Treatment in Patients with Severe Eosinophilic Asthma. N Engl J Med. 2014;371(13):1198–1207. doi: 10.1056/nejmoa1403290.

31. Ferguson G., FitzGerald J.M., Bleecker E.R., Laviolette M., Bernstein D., LaForce C. et al. Benralizumab for patients with mild to moderate, persistent asthma (BISE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med. 2017;5(7):568–576. doi: 10.1016/s2213-2600(17)30190-x.

32. Varricchi G., Bagnasco D., Ferrando M., Puggioni F., Passalacqua G., Canonica G.W. Mepolizumab in the management of severe eosinophilic asthma in adults: current evidence and practical experience. Ther Adv Respir Dis. 2017;11(1):40–45. doi: 10.1177/1753465816673303.

33. Tsukamoto N., Takahashi N., Itoh H., Pouliquen I. Pharmacokinetics and pharmacodynamics of mepolizumab, an anti-interleukin 5 monoclonal antibody, in healthy Japanese male subjects. Clin Pharmacol Drug Dev. 2016;5(2):102–108. doi: 10.1002/cpdd.205.

34. Pouliquen I.J., Kornmann O., Barton S.V., Price J.A., Ortega H.G. Characterization of the relationship between dose and blood eosinophil response following subcutaneous administration of mepolizumab. Int J Clin Pharmacol Ther. 2015;53(12):1015–1027. doi: 10.5414/cp202446.

35. Licari A., Manti S., Castagnoli R., Parisi G.F., Salpietro C., Leonardi S., Marseglia G.L. Targeted Therapy for Severe Asthma in Children and Adolescents: Current and Future Perspectives. Pediatric Drugs. 2019;21(4):215–237. doi: 10.1007/s40272-019-00345-7.

36. Logan J.K., Harinstein L., Muñoz M. Pediatric Postmarketing Pharmacovigilance Review: Cinqair (Reslizumab). Available at: https://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/PediatricAdvisoryCommittee/UCM610723.pdf.

37. Corren J., Weinstein S., Janka L., Zangrilli J., Garin M. Phase 3 Study of Reslizumab in Patients With Poorly Controlled Asthma: Effects Across a Broad Range of Eosinophil Counts. Chest. 2016;150(4):799–810. doi: 10.1016/j.chest.2016.03.018.

38. Bleecker E.R., FitzGerald J.M., Chanez P., Papi A., Weinstein S.F., Barker P. et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016;388(10056):2115–2127. doi: 10.1016/s0140-6736(16)31324-1.

39. Gupta A., Pouliquen I., Austin D., Price R.G., Kempsford R., Steinfeld J. et al. Subcutaneous mepolizumab in children aged 6 to 11 years with severe eosinophilic asthma. Pediatr Pulmonol. 2019;54(12):1957–1967. doi: 10.1002/ppul.24508.


Review

For citations:


Drozdov VN, Astapovskiy AA, Serebrova SY, Shikh EV, Komissarenko IA. Clinical efficacy of mepolizumab in the treatment of severe eosinophilic asthma in children. Meditsinskiy sovet = Medical Council. 2020;(18):115-121. (In Russ.) https://doi.org/10.21518/2079-701X-2020-18-115-121

Views: 597


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2079-701X (Print)
ISSN 2658-5790 (Online)