The use of a long-acting muscarinic antagonist in the treatment of asthma: A tertiary asthma center experience
Main Article Content
Keywords
asthma, asthma control, asthma phenotype, forced expiratory volume in 1 s (FEV1), long-acting muscarinic antagonist
Abstract
Introduction: We aimed to investigate the frequency and sociodemographic and clinical distinguishing features of asthmatic patients in whom long-acting muscarinic antagonists (LAMA) were added to maintenance therapy in our clinic.
Methods: In this cross-sectional study, data on sociodemographic, phenotypic, and clinical characteristics of patients with asthma using Steps 4 and 5 medications, who were followed up in our center for at least 1 year, were obtained from file records. Whether the patients received add-on LAMA for at least 6 months was also noted.
Results: A total of 279 patients with asthma using Steps 4 and 5 medications (female/male: 215/64) with a mean age of 50.84 ± 12.42 years were included in the study. Seventy-nine (28.3%) patients (female/male: 60/19) with a mean age of 52.45 ± 11.61 years used LAMA as an add-on treatment; 28 (37.8%) at Step 4 and 51 (24.8%) at Step 5. In Steps 4 and 5, there was no difference in terms of age, sex, body mass index, smoking status, being allergic or eosinophilic, phenotype, and asthma onset between patients with and without add-on LAMA. Asthma control in the previous year was better, and minimum forced expiratory volume in 1s (FEV1) was lower in patients with LAMA than in those without in Step 4 (P = 0.001 and P = 0.030, respectively). In Step 5, the rate of being well-controlled was higher in those without add-on LAMA (P < 0.001). The number of exacerbations in the previous year was higher, and minimum and maximum FEV1 were lower in patients with add-on LAMA (P < 0.001 and P < 0.001, respectively).
Conclusion: Our study showed that add-on LAMA treatment was effective in increasing asthma control in patients using Step 4 medication independent of baseline characteristics and asthma phenotype.
References
2 Ohta S, Oda N, Yokoe T, Tanaka A, Yamamoto Y, Watanabe Y, et al. Effect of tiotropium bromide on airway inflammation and remodelling in a mouse model of asthma. Clin Exp Allergy. 2010;40(8):1266–75. 10.1111/j.1365-2222.2010.03478.x
3 Buels KS, Fryer AD. Muscarinic receptor antagonists: Effects on pulmonary function. Handb Exp Pharmacol. 2012(208):317–41. 10.1007/978-3-642-23274-9_14
4 Kerstjens HA, Engel M, Dahl R, Paggiaro P, Beck E, Vandewalker M, et al. Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med. 2012;367(13):1198–207. 10.1056/NEJMoa1208606
5 Kerstjens HA, Moroni-Zentgraf P, Tashkin DP, Dahl R, Paggiaro P, Vandewalker M, et al. Tiotropium improves lung function, exacerbation rate, and asthma control, independent of baseline characteristics including age, degree of airway obstruction, and allergic status. Respir Med. 2016;117:198–206. 10.1016/j.rmed.2016.06.013
6 FDA [Internet]. Spiriva® Respimat® new drug application approval by FDA. [updated in February 2024]. Available from: https://www.accessdata.fda.gov/drugsatfda_docsappletter2015/207070Orig1s000ltr.Pdf (Accessed April 20, 2024)
7 Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2015. Available from: https://ginasthma.org (Accessed April 20, 2024)
8 Abadoglu O, Berk S. Tiotropium may improve asthma symptoms and lung function in asthmatic patients with irreversible airway obstruction: The real-life data. Clin Respir J. 2016;10(4):421–7. 10.1111/crj.12230
9 Price D, Kaplan A, Jones R, Freeman D, Burden A, Gould S, et al. Long-acting muscarinic antagonist use in adults with asthma: Real-life prescribing and outcomes of add-on therapy with tiotropium bromide. J Asthma Allergy. 2015;8:1–13. 10.2147/JAA.S76639
10 Gessner C, Kornmann O, Maspero J, van Zyl-Smit R, Krüll M, Salina A, et al. Fixed-dose combination of indacaterol/glycopyrronium/mometasone furoate once-daily versus salmeterol/fluticasone twice-daily plus tiotropium once-daily in patients with uncontrolled asthma: A randomised, Phase IIIb, non-inferiority study (ARGON). Respir Med. 2020;170:106021. 10.1016/j.rmed.2020.106021
11 Kerstjens HAM, Maspero J, Chapman KR, van Zyl-Smit RN, Hosoe M, Tanase AM, et al. Once-daily, single-inhaler mometasone-indacaterol-glycopyrronium versus mometasone-indacaterol or twice-daily fluticasone-salmeterol in patients with inadequately controlled asthma (IRIDIUM): A randomised, double-blind, controlled phase 3 study. Lancet Respir Med. 2020;8(10):1000–12. 10.1016/S2213-2600(20)30190-9
12 Virchow JC, Kuna P, Paggiaro P, Papi A, Singh D, Corre S, et al. Single inhaler extrafine triple therapy in uncontrolled asthma (TRIMARAN and TRIGGER): Two double-blind, parallel-group, randomised, controlled phase 3 trials. Lancet. 2019;394(10210):1737–49. 10.1016/S0140-6736(19)32215-9
13 Lee LA, Bailes Z, Barnes N, Boulet LP, Edwards D, Fowler A, et al. Efficacy and safety of once-daily single-inhaler triple therapy (FF/UMEC/VI) versus FF/VI in patients with inadequately controlled asthma (CAPTAIN): A double-blind, randomised, phase 3A trial. Lancet Respir Med. 2021;9(1):69–84. 10.1016/S2213-2600(20)30389-1
14 Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2021. Available from: https://ginasthma.org/wp-content/uploads/2021/05/GINA-Main-Report-2021-V2-WMS.pdf (Accessed April 20, 2024)
15 Halpin DMG, Hamelmann EH, Frith PA, Moroni-Zentgraf PM, van Hecke B, Unseld A, et al. Comparative responses in lung function measurements with tiotropium in adolescents and adults, and across asthma severities: A post hoc analysis. Pulm Ther. 2020;6(1):131–40. 10.1007/s41030-020-00113-w
16 Ohta K, Ichinose M, Tohda Y, Engel M, Moroni-Zentgraf P, Kunimitsu S, et al. Long-term once-daily tiotropium Respimat® is well tolerated and maintains over 52 weeks in patients with symptomatic asthma in Japan: A randomised, placebo-controlled study. PLoS One. 2015;10(4):e0124109. 10.1371/journal.pone.0124109
17 Casale TB, Bateman ED, Vandewalker M, Virchow JC, Schmidt H, Engel M, et al. Tiotropium respimat add-on is efficacious in symptomatic asthma, independent of T2 phenotype. J Allergy Clin Immunol Pract. 2018;6(3):923-35.e9. 10.1016/j.jaip.2017.08.037
18 Kim LHY, Saleh C, Whalen-Browne A, O’Byrne PM, Chu DK. Triple vs dual inhaler therapy and asthma outcomes in moderate to severe asthma: A systematic review and meta-analysis. JAMA. 2021;325(24):2466–79. 10.1001/jama.2021.7872
19 van Zyl-Smit RN, Kerstjens HAM, Maspero J, Tanase AM, Lawrence D, Mezzi K, et al. Triple therapy with mometasone/indacaterol/glycopyrronium or doubling the ICS/LABA dose in GINA Step 4: IRIDIUM analyses. Pulm Ther. 2023;9(3):395–409. 10.1007/s41030-023-00234-y
20 Wechsler ME, Menzies-Gow A, Brightling CE, Kuna P, Korn S, Welte T, et al. Evaluation of the oral corticosteroid-sparing effect of tezepelumab in adults with oral corticosteroid-dependent asthma (SOURCE): A randomised, placebo-controlled, phase 3 study. Lancet Respir Med. 2022;10(7):650–60. 10.1016/S2213-2600(21)00537-3
21 Korn S, Bourdin A, Chupp G, Cosio BG, Arbetter D, Shah M, et al. Integrated safety and efficacy among patients receiving benralizumab for up to 5 years. J Allergy Clin Immunol Pract. 2021;9(12):4381–92.e4. 10.1016/j.jaip.2021.07.058
22 Wechsler ME, Ford LB, Maspero JF, Pavord ID, Papi A, Bourdin A, et al. Long-term safety and efficacy of dupilumab in patients with moderate-to-severe asthma (TRAVERSE): An open-label extension study. Lancet Respir Med. 2022;10(1):11–25. 10.1016/S2213-2600(21)00322-2
23 Bavbek S, Fernandez P, Mahboub B, Al-Lehebi RO, Maturu VN, Rosales DJC, et al. Multi-country self-controlled study of exacerbation rates in severe asthma patients treated with mepolizumab: NEST interim analysis. Eur Resp J. 2023;62(Suppl 67):PA1907. 10.1183/13993003.congress-2023.PA1907
24 Aydın Ö, Sözener Z, Soyyiğit Ş, Kendirlinan R, Gençtürk Z, Mısırlıgil Z, et al. Omalizumab in the treatment of allergic bronchopulmonary aspergillosis: One center’s experience with 14 cases. Allergy Asthma Proc. 2015;36(6):493–500. 10.2500/aap.2015.36.3909
25 Çelebi Sözener Z, Aydın Ö, Mısırlıgil Z, Mungan D, Demirel YS, Çelik GE, et al. Omalizumab in non-allergic Asthma: A report of 13 cases. J Asthma. 2018;55(7):756-63. 10.1080/02770903.2017.1362427
26 Celebi Sozener Z, Gorgulu B, Mungan D, Sin BA, Misirligil Z, Aydin O, et al. Omalizumab in the treatment of eosinophilic granulomatosis with polyangiitis (EGPA): single-center experience in 18 cases. World Allergy Organ J. 2018;11(1):39. 10.1186/s40413-018-0217-0
27 Özdel Öztürk B, Yavuz Z, Eraslan D, Mungan D, Demirel YS, Aydın Ö, et al. Mepolizumab is an effective option in severe eosinophilic asthma regardless of baseline features: Single-center real-life data. Int Arch Allergy Immunol. 2022;183(5):526–38. 10.1159/000520725
28 Spain CV, Dayal P, Ding Y, Iribarren C, Omachi TA, Chen H. Usage of long-acting muscarinic antagonists and biologics as add-on therapy for patients in the United States with moderate-to-severe asthma. J Asthma. 2022;59(6):1237–47. 10.1080/02770903.2021.1922915