The Long-Term Omalizumab Therapy in Children with Severe Persistent Uncontrolled Asthma: Evaluation of the Outcomes According to the Data of the Hospital Patient Registry

Background: Patient registries help to obtain relevant information about the peculiarities of certain diseases, as well as the safety and effectiveness of different medical technologies. Moreover, it allows conducting a continuous monitoring in a studied group. Objective: to analyze the effectiveness and safety of a long-term target therapy with Omalizumab (more than 4 years) in children with severe persistent uncontrolled asthma based on the electronic clinical cases database (registry). Methods. The outcomes of the treatment were evaluated based on the data from the registry of patients with severe uncontrolled asthma. Time period: November 2007- March 2018. The main goal of the research was to identify the number of patients who achieved the disease control (20 points С-АСТ-test in children aged 6–11 years or 25 points АСТ-test in children aged 12–17 years) at least in one of the time points — in 4; 6; 12 or 48 months. Results. The results of the treatment of 26 children were analyzed (males — 73%), median age — 17 years. The posology of Omalizumab was 75 to 600 mg, median (Me) 300 mg [225; 375]. Asthma control test (ACT) before the start of the treatment was 14 points (Me 14 [12; 17,5], in 48 mo — 21 points (Me 22 [20; 24]; p=0,0017). The decrease of the amount of the daily therapy was demonstrated. The median dose of the ICS (fluticasone) was 575 mcg/day (Me 500 [437,5; 750]) before the start of the treatment, in 48 mo — 492 mcg/day (Me 500 [250; 562,5]; p=0,066). The decrease of the number of exacerbations and the use of SABA from 12 (Me 10,5 [9,75; 13,25]) to 0,8 times/month (Me [1; 0;1]) was observed after 4 years of treatment (р=0,000). No adverse events were observed. Conclusions. Long-term therapy with Omalizumab increases the disease control in children with severe persistent asthma. The registry as a continuous monitoring tool enables to conduct a complex evaluation of the effectiveness and safety of the treatment.

1. ginasthma.org [Internet]. Global Initiative for Asthma. Glo bal Strategy for Asthma Management and Prevention, revised 2017 [cited 2017 May 17]. Available from: www.ginasthma.org/.

2. Baranov AA, Namazova-Baranova LS, Khaitov RM, et al. Federal’nye klinicheskie rekomendatsii po okazaniyu meditsinskoi pomoshchi detyam s bronkhial’noi astmoi. Moscow; 2016. 33 p. (In Russ).

3. Ilina NI, Namazova-Baranova LS, Emelianov AV, et al. Algorhythm of immunobiologic agents usage in the treatment of severe atopic bronchial asthma in Russia (consensus document). Rossiiskii allergologicheskii zhurnal. 2014;(4):26–27. (In Russ).

4. Papadopoulos NG, Arakawa H, Carlsen KH, et al. International consensus on (ICON) pediatric asthma. Allergy. 2012;67(8):976– 997. doi: 10.1111/j.1398-9995.2012.02865.x.

5. Niven RM, Saralaya D, Chaudhuri R, et al. Impact of omalizumab on treatment of severe allergic asthma in UK clinical practice: a UK multicentre observational study (the APEX II study). BMJ Open. 2016;6(8):e011857. doi: 10.1136/bmjopen-2016-011857.

6. Braunstahl GJ, Chen CW, Maykut R, et al. The eXpeRience registry: the ‘real-world’ effectiveness of omalizumab in allergic asthma. Respir Med. 2013;107(8):1141–1151. doi: 10.1016/j. rmed.2013.04.017.

7. Schleich F, Brusselle G, Louis R, et al. Heterogeneity of phenotypes in severe asthmatics. The Belgian Severe Asthma Registry (BSAR). Respir Med. 2014;108(12):1723–1732. doi: 10.1016/j. rmed.2014.10.007.

8. Kupryś-Lipińska I, Majak P, Molinska J, Kuna P. Effectiveness of the Polish program for the treatment of severe allergic asthma with omalizumab: a single-center experience. BMC Pulm Med. 2016;16(1):61. doi: 10.1186/s12890-016-0224-2.

9. Ledford D, Busse W, Trzaskoma B, et al. A randomized multi-center study evaluating Xolair persistence of response after longterm therapy. J Allergy Clin Immunol. 2017;140(1):162–169.e2. doi: 10.1016/j.jaci.2016.08.054.

10. Greenhalgh T. How to read a paper. The basics of evidence-based medicine. Transl. from English. Ed by Denisov I.N., Saitulov K.I. 3rd ed. Moscow: GEOTAR-Media; 2008. 288 p. (In Russ).

11. Melikhov OG. Klinicheskie issledovaniya. 3rd ed, updated. Moscow: Atmosfera; 2013. 200 p. (In Russ).

12. Sousa AS, Pereira AM, Fonseca JA, et al. Severe Asthma Specialist Network (Rede de Especialistas de Asma Grave REAG). Asthma control and exacerbations in patients with severe asthma treated with omalizumab in Portugal. Rev Port Pneumol (2006). 2015;21(6):327–333. doi: 10.1016/j.rppnen.2015.03.002.

13. Gouder C, West LM, Montefort S. The real-life clinical effects of 52 weeks of omalizumab therapy for severe persistent allergic asthma. Int J Clin Pharm. 2015;37(1):36–43. doi: 10.1007/ s11096-014-0034-7.

14. J Asthma. 2011;48(4):387–392. doi: 10.3109/02770903. 2011.561512.

15. Chen HC, Huang CD, Chang E, Kuo HP. Efficacy of omalizumab (Xolair®) in patients with moderate to severe predominately-chronic oral steroid dependent asthma in Taiwan: a retrospective, population-based database cohort study. BMC Pulm Med. 2016;16:3. doi: 10.1186/s12890-015-0156-2.

16. Kupryś-Lipińska I, Kuna P. Loss of asthma control after cessation of omalizumab treatment: real life data. Postep Derm Alergol. 2014;31(1):1–5. doi: 10.5114/pdia.2014.40553.

17. Deschildre A, Marguet C, Salleron J, et al. Add-on omalizumab in children with severe allergic asthma: a 1-year real life survey. Eur Respir J. 2013;42(5):1224–1233. doi: 10.1183/09031936.00149812.

18. Normansell R, Walker S, Milan SJ, et al. Omalizumab for asthma in adults and children. Cochrane Database Syst Rev. 2014;(1):CD003559. doi: 10.1002/14651858.CD003559.pub4. Available from: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003559.pub4/full

19. Kulichenko TV, Namazova-Baranova LS, Torshkhoeva RM, et al. Anti-IgE therapy for severe asthma in children: two-year trial. Pediatric pharmacology. 2010;7(3):57–65. (In Russ).

20. Vishneva EA, Namazova-Baranova LS, Antonova EV, Smirnov VI. The First Russian Information System — database of clinical cases of persistent bronchial asthma in pediatric patients. Pediatric pharmacology. 2015;12(1):18–21. (In Russ).] doi: 10.15690/pf.v12i1.1242.

21. Namazova-Baranova LS, Vishneva EA, Dobrynina EA, et al. Primary results of longterm dynamic monitoring of children with bronchial asthma of uncontrolled severe persistent course. Pediatric pharmacology. 2016;13(6):554–559. (In Russ).] doi: 10.15690/pf.v13i6.1668.

22. Entsiklopediya lekarstv i tovarov aptechnogo assortimenta. Omalizumab (Omalizumab): instruktsiya, primenenie i formula (In Russ).] Доступно по: http://www.rlsnet.ru/mnn_index_id_3748. htm. Ссылка активна на 22.12.2017.

23. Saji J, Yamamoto T, Arai M, et al. Efficacy of long-term omalizumab therapy in patients with severe asthma. Respir Investig. 2017;55(2):114–120. doi: 10.1016/j.resinv.2016.11.002.

24. Gemicioğlu B, Çalışkaner Öztürk B, Duman B. Comparison of allergic asthma patients treated with omalizumab and non-allergic patients treated with continuous oral corticosteroids: results of five-year follow-up therapies. Tuberk Toraks. 2016;64(2):97–104. doi: 10.5578/tt.22074.

25. Tat TS, Cilli A. Evaluation of long-term safety and efficacy of omalizumab in elderly patients with uncontrolled allergic asthma. Ann Allergy Asthma Immunol. 2016;117(5):546–549. doi: 10.1016/j.anai.2016.09.006.

26. Sposato B, Scalese M, Latorre M, et al. Effects of omalizumab in severe asthmatics across ages: a real life Italian experience. Respir Med. 2016;119:141–149. doi: 10.1016/j. rmed.2016.09.005.

27. Tzortzaki EG, Georgiou A, Kampas D, et al. Long-term omalizumab treatment in severe allergic asthma: the South-Eastern Mediterranean «real-life» experience. Pulm Pharmacol Ther. 2012;25(1):77–82. doi: 10.1016/j.pupt.2011.11.004.

28. Ledford D, Busse W, Trzaskoma B, et al. A randomized multicenter study evaluating Xolair persistence of response after long-term therapy. J Allergy Clin Immunol. 2017;140(1):162–169. doi: 10.1016/j.jaci.2016.08.054.

29. Menzella F, Galeone C, Formisano D, et al. Real-life efficacy of omalizumab after 9 years of follow-up. Allergy Asthma Immunol Res. 2017;9(4):368–372. doi: 10.4168/aair.2017.9.4.368.