Real-world efficacy and safety of dupilumab for patients with moderate-to-severe asthma: a retrospective study_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

 WANG Wen , GUO Yue , LI Jieying , WANG Feiran

Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, and Beijing Chao-yang Hospital, Capital Medical University, Beijing 100020, P. R. China;

Corresponding author：

WANG Wen, Email: wangw_cyhospital@163.com

Keywords：

Dupilumab; asthma; type 2 inflammation; real-world study

DOI：

10.7507/1671-6205.202305069

Video：

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Objective To evaluate the efficacy and safety of dupilumab in the treatment of moderate-to-severe asthma. Methods A retrospective study was conducted among patients with moderate-to-severe asthma who were treated with dupilumab and inhaled corticosteroids (ICS) combined with long acting beta-agonist (LABA) in Department of Respiratory, Beijing Chao-yang Hospital from May, 2021 to April, 2022. Paired t-test or Mann-Whitney U test was applied to compare the Asthma Control Test (ACT) scores, number of acute exacerbations per year, type 2 inflammatory biomarkers, blood total IgE and results of pulmonary function tests, including forced vital capacity (FVC), forced expiratory volume in 1 second (FEV₁), FEV₁ as percentage of predicted (FEV₁%pred), FEV₁/FVC, peak expiratory flow (PEF), maximal expiratory flows (MEF) at 75% (MEF75), 50% (MEF50) and 25% (MEF25) of the vital capacity PEF, and maximal mid-expiratory flow (MMEF) or FEF_25%-75%, at the end of follow-up with those before treatment. Adverse reactions were recorded during the treatment. Results A total of 47 patients with moderate-to-severe asthma were included in the study, among them 17 and 30 received treatment with dupilumab or ICS/LABA. At the time of 12 months after treatment with dupilumab, the patients' ACT score and pulmonary function tests were significantly increased compared with those at the baseline. In contrast, patients' fractional exhaled nitric oxide (FeNO), blood total IgE, blood basophil counts and annual acute exacerbations were significantly decreased in comparison with those at the baseline. The doses of oral corticosteroids added by 7 patients at the baseline was gradually reduced and finally discontinued after treatment of dupilumab. There were 4, 2, 1 and 1 patients developed injection site reaction, pruritus, erythema and fatigue, respectively, which were mild and recovered without treatment. There was no serious adverse reaction observed, and only 1 case developed herpes zoster which was recovered after treatment. Conclusion Dupilumab shows marked efficacy in the treatment of moderate-to-severe asthma with favorable safety.

Citation： WANG Wen, GUO Yue, LI Jieying, WANG Feiran. Real-world efficacy and safety of dupilumab for patients with moderate-to-severe asthma: a retrospective study. Chinese Journal of Respiratory and Critical Care Medicine, 2023, 22(10): 685-691. doi: 10.7507/1671-6205.202305069 Copy

1.	中华医学会呼吸病学分会哮喘学组. 支气管哮喘防治指南(2020版). 中华结核和呼吸杂志, 2020, 43(12): 1023-1048.
2.	Huang KW, Yang T, Xu JY, et al. Prevalence, risk factors, and management of asthma in China: a national cross-sectional study. Lancet, 2019, 394(10196): 407-418.
3.	Woodruff PG, Modrek B, Choy DF, et al. T-helper type 2-driven inflammation defines major subphenotypes of asthma. Am J Respir Crit Care Med, 2009, 180(5): 388-395.
4.	Brusselle GG, Koppelman GH. Biologic therapies for severe asthma. N Engl J Med, 2022, 386(2): 157-171.
5.	Frøssing L, Silberbrandt A, Von Bülow A, et al. The prevalence of subtypes of type 2 inflammation in an unselected population of patients with severe asthma. J Allergy Clin Immunol Pract, 2021, 9(3): 1267-1275.
6.	Pelaia C, Vatrella A, Gallelli L, et al. Dupilumab for the treatment of asthma. Expert Opin Biol Ther, 2017, 17(12): 1565-1572.
7.	Peters MC, Wenzel SE. Intersection of biology and therapeutics: type 2 targeted therapeutics for adult asthma. Lancet, 2020, 395(10221): 371-383.
8.	Castro M, Corren J, Pavord ID, et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N Engl J Med, 2018, 378(26): 2486-2496.
9.	Wenzel S, Castro M, Corren J, et al. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting β₂ agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. Lancet, 2016, 388(10039): 31-44.
10.	Wenzel S, Ford L, Pearlman D, et al. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med, 2013, 368(26): 2455-2466.
11.	Seegräber M, Srour J, Walter A, et al. Dupilumab for treatment of atopic dermatitis. Expert Rev Clin Pharmacol, 2018, 11(5): 467-474.
12.	Bachert C, Hellings PW, Mullol J, et al. Dupilumab improves health-related quality of life in patients with chronic rhinosinusitis with nasal polyposis. Allergy, 2020, 75(1): 148-157.
13.	Reddel HK, Bacharier LB, Bateman ED, et al. Global Initiative for Asthma Strategy 2021: executive summary and rationale for key changes. Eur Respir J, 2021, 59(1): 2102730.
14.	Numata T, Araya J, Miyagawa H, et al. Real-world effectiveness of dupilumab for patients with severe asthma: a retrospective study. J Asthma Allergy, 2022, 15: 395-405.
15.	Dupin C, Belhadi D, Guilleminault L, et al. Effectiveness and safety of dupilumab for the treatment of severe asthma in a real-life French multi-centre adult cohort. Clin Exp Allergy, 2020, 50(7): 789-798.
16.	Chung KF. Dupilumab: a potential new treatment for severe asthma. Lancet, 2016, 388(10039): 3-4.
17.	Le Floc'h A, Allinne J, Nagashima K, et al. Dual blockade of IL-4 and IL-13 with dupilumab, an IL-4Rα antibody, is required to broadly inhibit type 2 inflammation. Allergy, 2020, 75(5): 1188-1204.
18.	Darveaux J, Busse WW. Biologics in asthma--the next step toward personalized treatment. J Allergy Clin Immunol Pract, 2015, 3(2): 152-160.
19.	Harries TH, Rowland V, Corrigan CJ, et al. Blood eosinophil count, a marker of inhaled corticosteroid effectiveness in preventing COPD exacerbations in post-hoc RCT and observational studies: systematic review and meta-analysis. Respir Res, 2020, 21(1): 3.
20.	Thibodeaux Q, Smith MP, Ly K, et al. A review of dupilumab in the treatment of atopic diseases. Hum Vaccin Immunother, 2019, 15(9): 2129-2139.
21.	Harb H, Chatila TA. Mechanisms of dupilumab. Clin Exp Allergy, 2020, 50(1): 5-14.
22.	Zhou BY, Dong JL, Liang SR, et al. The changes of IgE levels in type 2 inflammatory diseases after treatment of dupilumab: a systematic review and meta-analysis. Expert Rev Clin Pharmacol, 2022, 15(10): 1233-1242.
23.	Mümmler C, Kemmerich B, Behr J, et al. Differential response to biologics in a patient with severe asthma and ABPA: a role for dupilumab? Allergy Asthma Clin Immunol, 2020, 16: 55.
24.	Agarwal R, Sehgal IS, Dhooria S, et al. Allergic bronchopulmonary aspergillosis. Indian J Med Res, 2020, 151(6): 529-549.
25.	Schuyler M. The Th1/Th2 paradigm in allergic bronchopulmonary aspergillosis. J Lab Clin Med, 1998, 131(3): 194-196.
26.	Romani L. Immunity to fungal infections. Nat Rev Immunol, 2011, 11(4): 275-288.
27.	Nishimura T, Okano T, Naito M, et al. Complete withdrawal of glucocorticoids after dupilumab therapy in allergic bronchopulmonary aspergillosis: a case report. World J Clin Cases, 2021, 9(23): 6922-6928.
28.	van der Veer T, Dallinga MA, van der Valk JPM, et al. Reduced exacerbation frequency and prednisone dose in patients with ABPA and asthma treated with dupilumab. Clin Transl Allergy, 2021, 11(10): e12081.

1. 中华医学会呼吸病学分会哮喘学组. 支气管哮喘防治指南(2020版). 中华结核和呼吸杂志, 2020, 43(12): 1023-1048.
2. Huang KW, Yang T, Xu JY, et al. Prevalence, risk factors, and management of asthma in China: a national cross-sectional study. Lancet, 2019, 394(10196): 407-418.
3. Woodruff PG, Modrek B, Choy DF, et al. T-helper type 2-driven inflammation defines major subphenotypes of asthma. Am J Respir Crit Care Med, 2009, 180(5): 388-395.
4. Brusselle GG, Koppelman GH. Biologic therapies for severe asthma. N Engl J Med, 2022, 386(2): 157-171.
5. Frøssing L, Silberbrandt A, Von Bülow A, et al. The prevalence of subtypes of type 2 inflammation in an unselected population of patients with severe asthma. J Allergy Clin Immunol Pract, 2021, 9(3): 1267-1275.
6. Pelaia C, Vatrella A, Gallelli L, et al. Dupilumab for the treatment of asthma. Expert Opin Biol Ther, 2017, 17(12): 1565-1572.
7. Peters MC, Wenzel SE. Intersection of biology and therapeutics: type 2 targeted therapeutics for adult asthma. Lancet, 2020, 395(10221): 371-383.
8. Castro M, Corren J, Pavord ID, et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N Engl J Med, 2018, 378(26): 2486-2496.
9. Wenzel S, Castro M, Corren J, et al. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting β₂ agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. Lancet, 2016, 388(10039): 31-44.
10. Wenzel S, Ford L, Pearlman D, et al. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med, 2013, 368(26): 2455-2466.
11. Seegräber M, Srour J, Walter A, et al. Dupilumab for treatment of atopic dermatitis. Expert Rev Clin Pharmacol, 2018, 11(5): 467-474.
12. Bachert C, Hellings PW, Mullol J, et al. Dupilumab improves health-related quality of life in patients with chronic rhinosinusitis with nasal polyposis. Allergy, 2020, 75(1): 148-157.
13. Reddel HK, Bacharier LB, Bateman ED, et al. Global Initiative for Asthma Strategy 2021: executive summary and rationale for key changes. Eur Respir J, 2021, 59(1): 2102730.
14. Numata T, Araya J, Miyagawa H, et al. Real-world effectiveness of dupilumab for patients with severe asthma: a retrospective study. J Asthma Allergy, 2022, 15: 395-405.
15. Dupin C, Belhadi D, Guilleminault L, et al. Effectiveness and safety of dupilumab for the treatment of severe asthma in a real-life French multi-centre adult cohort. Clin Exp Allergy, 2020, 50(7): 789-798.
16. Chung KF. Dupilumab: a potential new treatment for severe asthma. Lancet, 2016, 388(10039): 3-4.
17. Le Floc'h A, Allinne J, Nagashima K, et al. Dual blockade of IL-4 and IL-13 with dupilumab, an IL-4Rα antibody, is required to broadly inhibit type 2 inflammation. Allergy, 2020, 75(5): 1188-1204.
18. Darveaux J, Busse WW. Biologics in asthma--the next step toward personalized treatment. J Allergy Clin Immunol Pract, 2015, 3(2): 152-160.
19. Harries TH, Rowland V, Corrigan CJ, et al. Blood eosinophil count, a marker of inhaled corticosteroid effectiveness in preventing COPD exacerbations in post-hoc RCT and observational studies: systematic review and meta-analysis. Respir Res, 2020, 21(1): 3.
20. Thibodeaux Q, Smith MP, Ly K, et al. A review of dupilumab in the treatment of atopic diseases. Hum Vaccin Immunother, 2019, 15(9): 2129-2139.
21. Harb H, Chatila TA. Mechanisms of dupilumab. Clin Exp Allergy, 2020, 50(1): 5-14.
22. Zhou BY, Dong JL, Liang SR, et al. The changes of IgE levels in type 2 inflammatory diseases after treatment of dupilumab: a systematic review and meta-analysis. Expert Rev Clin Pharmacol, 2022, 15(10): 1233-1242.
23. Mümmler C, Kemmerich B, Behr J, et al. Differential response to biologics in a patient with severe asthma and ABPA: a role for dupilumab? Allergy Asthma Clin Immunol, 2020, 16: 55.
24. Agarwal R, Sehgal IS, Dhooria S, et al. Allergic bronchopulmonary aspergillosis. Indian J Med Res, 2020, 151(6): 529-549.
25. Schuyler M. The Th1/Th2 paradigm in allergic bronchopulmonary aspergillosis. J Lab Clin Med, 1998, 131(3): 194-196.
26. Romani L. Immunity to fungal infections. Nat Rev Immunol, 2011, 11(4): 275-288.
27. Nishimura T, Okano T, Naito M, et al. Complete withdrawal of glucocorticoids after dupilumab therapy in allergic bronchopulmonary aspergillosis: a case report. World J Clin Cases, 2021, 9(23): 6922-6928.
28. van der Veer T, Dallinga MA, van der Valk JPM, et al. Reduced exacerbation frequency and prednisone dose in patients with ABPA and asthma treated with dupilumab. Clin Transl Allergy, 2021, 11(10): e12081.

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