Early responders within seven days of dupilumab treatment for severe asthma evaluated by patient-reported outcome: a pilot study

  • Nozomi Tani Department of Respiratory Medicine, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan.
  • Nobutaka Kataoka Department of Respiratory Medicine, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan.
  • Yusuke Kunimatsu Department of Respiratory Medicine, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan. https://orcid.org/0000-0002-8667-8044
  • Yusuke Tachibana Department of Respiratory Medicine, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan.
  • Takumi Sugimoto Department of Respiratory Medicine, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan.
  • Izumi Sato Department of Respiratory Medicine, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan.
  • Yuri Ogura Department of Respiratory Medicine, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan.
  • Kazuki Hirose Department of Respiratory Medicine, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan.
  • Takayuki Takeda | dyckw344@yahoo.co.jp Department of Respiratory Medicine, Japanese Red Cross Kyoto Daini Hospital, Kyoto, Japan. https://orcid.org/0000-0002-8375-6940


Background: The management of severe asthma-associated symptoms is essential since they are distressing to the affected patients, and also greatly impair their quality of life. Dupilumab, a monoclonal antibody, blocks interleukin (IL)-4 and IL-13 signaling, both of which are crucial in acquired and innate immunity pathways through fast signal transduction, leading to an early response to treatment. Although rapid improvement within 1–3 days after dupilumab treatment was observed in moderate-to-severe atopic dermatitis, an early response within 7 days of dupilumab treatment in severe asthma has not been reported. 
Methods: Twelve consecutive patients with severe asthma who were newly treated with dupilumab between July 2019 and April 2020 were retrospectively investigated. We evaluated the early response (within 7 days) of patients with severe asthma receiving dupilumab therapy. Asthma control test (ACT) and the daily ACT, which was modified from the ACT to evaluate daily symptoms associated with asthma, were adopted as patient-reported outcomes (PROs) at week 8 and within 7 days, respectively. Patients were stratified into early responders (7 days), late responders (week 8), and non-responders without significant improvement in PROs. Descriptive statistics were adopted due to the limited number of patients.
Results: Four of these 12 patients were early responders, with the following baseline characteristics: body mass index, <25 kg/m2; without depression; baseline forced expiratory volume in 1 second, <1.50 L; and more than one exacerbation in 1 year. On the other hand, five were late responders, and 44.4% of the nine responders were early responders. The higher the eosinophilic count and/or FeNO did not show any relationship between the early responder and nonresponder.
Conclusions: The effect of dupilumab on severe asthma in patients with atopic features could be started earlier than 2 weeks, similar to atopic dermatitis. Daily ACT may be useful in monitoring the early efficacy of dupilumab in treating severe asthma.



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Global Initiative for Asthma, Global Strategy for Asthma Management and Prevention. Updated 2020. Accessed on: 26 June 2020. Available from: https://ginasthma.org/wp-content/uploads/2020/06/GINA-2020-report_20_06_04-1-wms.pdf

Hekking PP, Wener RR, Amelink M, Zwinderman AH, Bouvy ML, Bel EH. The prevalence of severe refractory asthma. J Allergy Clin Immunol 2015;135:896-902. DOI: https://doi.org/10.1016/j.jaci.2014.08.042

Chipps BE, Haselkorn T, Paknis B, Ortiz B, Bleecker ER, Kianifard F, et al. Epidemiology and natural history of asthma: Outcomes and Treatment Regimens Study Group. More than a decade follow-up in patients with severe or difficult-to-treat asthma: The epidemiology and natural history of asthma: outcomes and treatment regimens (TENOR) II. J Allergy Clin Immunol 2018;141:1590-7. DOI: https://doi.org/10.1016/j.jaci.2017.07.014

Kupczyk M, ten Brinke A, Sterk PJ, Bel EH, Papi A, Chanez P, et al. Frequent exacerbators--A distinct phenotype of severe asthma. Clin Exp Allergy 2014;44:212-21. DOI: https://doi.org/10.1111/cea.12179

Mazalovic K, Jacoud F, Dima AL, Van Ganse E, Nolin M, C D, Zaba C. The Astro-Lab Group. Asthma exacerbations and socio-economic status in French adults with persistent asthma: A prospective cohort study. J Asthma 2018;55:1043-51. DOI: https://doi.org/10.1080/02770903.2017.1391280

Van Ganse E, Antonicelli L, Zhang, Q, Laforest L, Yin DD, Nocea G, et al. Asthma-related resource use and cost by GINA classification of severity in three European countries. Respir Med 2006;100:140-7. DOI: https://doi.org/10.1016/j.rmed.2005.03.041

Sullivan PW, Ghushchyan VH, Globe G, Schatz M. Oral corticosteroid exposure and adverse effects in asthmatic patients. J Allergy Clin Immunol 2018;141:110-6. DOI: https://doi.org/10.1016/j.jaci.2017.04.009

Fahy JV. Type 2 inflammation in asthma – present in most, absent in many. Nat Rev Immunol 2015;15:57-65. DOI: https://doi.org/10.1038/nri3786

Hirose K, Iwata A, Tamachi T, Nakajima H. Allergic airway inflammation: key players beyond the Th2 cell pathway. Immunol Rev 2017;278:145-61. DOI: https://doi.org/10.1111/imr.12540

Kuruvilla ME, Lee FE-H, Lee GB. Understanding asthma phenotypes, endotypes, and mechanism of disease. Clin Rev Allergy Immunol 2019;56:219-33. DOI: https://doi.org/10.1007/s12016-018-8712-1

D'Amato G, Stanziola A, Sanduzzi A, Liccardi G, Salzillo A, Vitale C, et al. Treating severe allergic asthma with anti-IgE monoclonal antibody (omalizumab): a review. Multidiscip Respir Med 2014;9:23. DOI: https://doi.org/10.1186/2049-6958-9-23

Menzella F, Lusuardi M, Galeone C, Zucchi L. Tailored therapy for severe asthma. Multidiscip Respir Med 2015;10:1. DOI: https://doi.org/10.1186/2049-6958-10-1

Busse WW. Biological treatments for severe asthma: A major advance in asthma care. Allergol Int. 2019; 68: 158-66. DOI: https://doi.org/10.1016/j.alit.2019.01.004

Barranco P, Phillips-Angles E, Dominguez-Ortega J, Quirce S. Dupilumab in the management of moderate-to-severe asthma: the data so far. Ther Clin Risk Manag 2017;13:1139-49. DOI: https://doi.org/10.2147/TCRM.S125964

Thaçi, D, L Simpson E, Deleuran M, Kataoka Y, Chen Z, Gadkari A, et al. Efficacy and safety of dupilumab monotherapy in adults with moderate-to-severe atopic dermatitis: A pooled analysis of two phase 3 randomized trials (LIBERTY AD SOLO 1 and LIBERTY AD SOLO 2). J Dermatol Sci 2019;94:266-75. DOI: https://doi.org/10.1016/j.jdermsci.2019.02.002

Silverberg JI, Yosipovitch G, Simpson EL, Kim BS, Wu JJ, Eckert L, et al. Dupilumab treatment results in early and sustained improvements in itch in adolescents and adults with moderate to severe atopic dermatitis: Analysis of the randomized phase 3 studies SOLO 1 and SOLO 2, AD ADOL, and CHRONOS. J Am Acad Dermatol 2020;82:1328-36. DOI: https://doi.org/10.1016/j.jaad.2020.02.060

Swigris JJ, Fairclough D. Patient-reported outcomes in idiopathic pulmonary fibrosis research. Chest 2012;142:291-7. DOI: https://doi.org/10.1378/chest.11-2602

Schatz M, Sorkness CA, Li JT, Marcus P, Murray JJ, Nathan RA, et al. Asthma Control Test: Reliability, validity, and responsiveness in patients not previously followed by asthma specialists. J Allergy Clin Immunol 2006;117:549-56. DOI: https://doi.org/10.1016/j.jaci.2006.01.011

Schatz M, Kosinski M, Yarlas AS, Hanlon J, Watson ME, Jhingran P. The minimally important difference of the asthma control test. J Allergy Clin Immunol 2009;124:719-23. DOI: https://doi.org/10.1016/j.jaci.2009.06.053

Yancey SW, Keene ON, Albers FC, Ortega H, Bates S, Bleecker ER, et al. Biomarkers for severe eosinophilic asthma. J Allergy Clin Immunol 2017;140:1509-18. DOI: https://doi.org/10.1016/j.jaci.2017.10.005

Bjermer L, Alving K, Diamant Z, Magnussen H, Pavord I, Piacentini G, et al. Current evidence and future research needs for FeNO measurement in respiratory diseases. Respir Med 2014;108 830-41. DOI: https://doi.org/10.1016/j.rmed.2014.02.005

Matsunaga K, Hamada K, Oishi K, Yano M, Yamaji Y, Hirano T. Factors associated with physician-patient discordance in the perception of asthma control. J Allergy Clin Immunol Pract 2019;7:2634-41. DOI: https://doi.org/10.1016/j.jaip.2019.04.046

Panagiotou M, Koulouris NG, Rovina N. Physical activity: A missing link in asthma care. J Clin Med 2020;9:706. DOI: https://doi.org/10.3390/jcm9030706

Castro M, Corren J, Pavord ID, Maspero J, Wenzel S, Rabe KF, et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N Engl J Med 2018;378:2486-96. DOI: https://doi.org/10.1056/NEJMoa1804092

Rabe KF, Nair P, Brusselle G, Maspero JF, Castro M, Sher L, et al. Efficacy and safety of dupilumab in glucocorticoid-dependent severe asthma. N Engl J Med 2018;378:2475-85. DOI: https://doi.org/10.1056/NEJMoa1804093

Corren J, Castro M, Chanez P, Fabbri L, Joish VN, Amin N, et al. Dupilumab improves symptoms, quality of life, and productivity in uncontrolled persistent asthma. Ann Allergy Asthma Immunol 2019;122:41-9. DOI: https://doi.org/10.1016/j.anai.2018.08.005

Barnes PJ. Targeting cytokines to treat asthma and chronic obstructive pulmonary disease. Nat Rev Immunol 2018;18:454-66. DOI: https://doi.org/10.1038/s41577-018-0006-6

LaPorte SL, Juo ZS, Vaclavikova J, Colf LA, Qi X, Heller NM, et al. Molecular and structural basis of cytokine receptor pleiotropy in the interleukin-4/13 system. Cell 2008;132:259-72. DOI: https://doi.org/10.1016/j.cell.2007.12.030

Oh CK, Geba GP, Molfino N. Investigational therapeutics targeting the IL-4/IL-13/STAT-6 pathway for the treatment of asthma. Eur Respir Rev 2010;19:46-54. DOI: https://doi.org/10.1183/09059180.00007609

Chiba Y, Goto K, Misawa M. Interleukin-13-induced activation of signal transducer and activator of transcription 6 is mediated by activation of Janus kinase 1 in cultured human bronchial smooth muscle cells. Pharmacol Rep 2012;64:454-8. DOI: https://doi.org/10.1016/S1734-1140(12)70788-0

Panettieri RA Jr, Sjöbring U, Péterffy A, Wessman P, Bowen K, Piper E, et al. Tralokinumab for severe, uncontrolled ssthma (STRATOS 1 and STRATOS 2): Two randomized, double-blind, placebo-controlled, phase 3 clinical trials. Lancet Respir Med 2018;6:511-25. DOI: https://doi.org/10.1016/S2213-2600(18)30184-X

Hanania NA, Korenblat P, Chapman KR, Bateman ED, Kopecky P, Paggiaro P, et al. Efficacy and safety of lebrikizumab in patients with uncontrolled asthma (LAVOLTA I and LAVOLTA II): Replicate, phase 3, randomized, double-blind, placebo-controlled trials. Lancet Respir Med 2016;4:781-96. DOI: https://doi.org/10.1016/S2213-2600(16)30265-X

Wenzel S, Wilbraham D, Fuller R, Getz EB, Longphre M. Effect of an interleukin-4 variant on late-phase asthmatic response to allergen challenge in asthmatic patients: results of two phase 2a studies. Lancet 2007;370:1422-31. DOI: https://doi.org/10.1016/S0140-6736(07)61600-6

Corren J, Busse W, Meltzer EO, Mansfield L, Bensch G, Fahrenholz J, et al. A randomized, controlled, phase 2 study of AMG 317, an IL-4Ralpha antagonist, in patients with asthma. Am J Respir Crit Care Med 2010;181:788-96. DOI: https://doi.org/10.1164/rccm.200909-1448OC

Original Research Articles
Conflict of interest statement
The authors declare that they have no competing interests, and all authors confirm accuracy
Asthma, daily ACT (asthma control test), dupilumab, early responder, severe asthma, quality of life
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How to Cite
Tani, N., Kataoka, N., Kunimatsu, Y., Tachibana, Y., Sugimoto, T., Sato, I., Ogura, Y., Hirose, K., & Takeda, T. (2021). Early responders within seven days of dupilumab treatment for severe asthma evaluated by patient-reported outcome: a pilot study. Multidisciplinary Respiratory Medicine, 16. https://doi.org/10.4081/mrm.2021.736