Yuji Tohda1, Yoichi Nakamura2, Takao Fujisawa3, Motohiro Ebisawa4, Kazuhiko Arima5, Masanori Miyata5, Yoshinori Takahashi5, Megan S Rice6, Yamo Deniz7, Paul Rowe8, Naimish Patel8, Neil M H Graham7, Ariel Teper8. 1. Kindai University Hospital, Osaka, Japan. Electronic address: tohda@med.kindai.ac.jp. 2. Yokohama City Minato Red Cross Hospital, Yokohama City, Japan. 3. Allergy Center, National Hospital Organization Mie National Hospital, Tsu, Japan. 4. Department of Allergy, Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, Sagamihara, Japan. 5. Sanofi K.K., Tokyo, Japan. 6. Sanofi, Cambridge, MA, USA. 7. Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA. 8. Sanofi, Bridgewater, NJ, USA.
Abstract
BACKGROUND: In the LIBERTY ASTHMA QUEST (ClinicalTrials.gov: NCT02414854) study, dupilumab 200 mg and 300 mg every 2 weeks vs matched-volume placebo reduced severe asthma exacerbations and improved lung function (FEV1), asthma control, and quality of life in patients with uncontrolled, moderate-to-severe asthma (N = 1902). Here, we examine the safety and efficacy of dupilumab in the subpopulation of Japanese patients who participated in QUEST (n = 114; 6%). METHODS: Endpoints assessed were annualized severe exacerbation rates and the effect of treatment over the 52-week treatment period on FEV1, asthma control, asthma-related quality of life, and markers of type 2 inflammation. RESULTS: In Japanese patients, dupilumab 200 and 300 mg every 2 weeks vs matched placebo reduced severe asthma exacerbation rates by 44% (P = 0.33) and 75% (P = 0.03), respectively, and improved FEV1 at Week 12 by 0.20 L (P = 0.05) and 0.17 L (P = 0.12). FEV1 improvements were rapid (by Week 2) and sustained throughout treatment. Significant and/or numerical improvements vs placebo in asthma control and quality of life were also observed throughout treatment. For each endpoint, greater efficacy was observed in patients with elevated baseline levels of type 2 inflammatory biomarkers (blood eosinophils or FeNO). Dupilumab treatment significantly reduced levels of FeNO and total IgE, but not blood eosinophils. CONCLUSIONS: In this subanalysis of QUEST, the efficacy and safety of dupilumab in Japanese patients was comparable to that observed in the overall intention-to-treat population, suggesting no variability in efficacy on the basis of Japanese ethnicity. (Funded by Sanofi and Regeneron Pharmaceuticals, Inc.; ClinicalTrials.gov number: NCT02414854).
RCT Entities:
BACKGROUND: In the LIBERTY ASTHMA QUEST (ClinicalTrials.gov: NCT02414854) study, dupilumab 200 mg and 300 mg every 2 weeks vs matched-volume placebo reduced severe asthma exacerbations and improved lung function (FEV1), asthma control, and quality of life in patients with uncontrolled, moderate-to-severe asthma (N = 1902). Here, we examine the safety and efficacy of dupilumab in the subpopulation of Japanese patients who participated in QUEST (n = 114; 6%). METHODS: Endpoints assessed were annualized severe exacerbation rates and the effect of treatment over the 52-week treatment period on FEV1, asthma control, asthma-related quality of life, and markers of type 2 inflammation. RESULTS: In Japanese patients, dupilumab 200 and 300 mg every 2 weeks vs matched placebo reduced severe asthma exacerbation rates by 44% (P = 0.33) and 75% (P = 0.03), respectively, and improved FEV1 at Week 12 by 0.20 L (P = 0.05) and 0.17 L (P = 0.12). FEV1 improvements were rapid (by Week 2) and sustained throughout treatment. Significant and/or numerical improvements vs placebo in asthma control and quality of life were also observed throughout treatment. For each endpoint, greater efficacy was observed in patients with elevated baseline levels of type 2 inflammatory biomarkers (blood eosinophils or FeNO). Dupilumab treatment significantly reduced levels of FeNO and total IgE, but not blood eosinophils. CONCLUSIONS: In this subanalysis of QUEST, the efficacy and safety of dupilumab in Japanese patients was comparable to that observed in the overall intention-to-treat population, suggesting no variability in efficacy on the basis of Japanese ethnicity. (Funded by Sanofi and Regeneron Pharmaceuticals, Inc.; ClinicalTrials.gov number: NCT02414854).
Authors: Andrew Gallagher; Michaela Edwards; Parameswaran Nair; Stewart Drew; Aashish Vyas; Rashmi Sharma; Paul A Marsden; Ran Wang; David Jw Evans Journal: Cochrane Database Syst Rev Date: 2021-10-19
Authors: Mohamed Sayed Zaazouee; Asmaa Gomaa Alwarraqi; Yasmine Adel Mohammed; Mohamed A Badheeb; Abdullah Mohamed Farhat; Mohammed Eleyan; Afnan Morad; Marwa Abdel-Aziz Zeid; Aya Shaban Mohamed; Hazem AbuEl-Enien; Ahmed Abdelalim; Ahmed Bostamy Elsnhory; Yasmin S M Hrizat; Nagat Taha Altahir; Doaa Atef; Alaa Ahmed Elshanbary; Khalaf F Alsharif; Khalid J Alzahrani; Mohammad Algahtani; Abdulrahman Theyab; Yousef M Hawsawi; Ahmed A Aldarmahi; Mohamed M Abdel-Daim Journal: Front Pharmacol Date: 2022-10-03 Impact factor: 5.988