Effectiveness of the P2X3 Antagonist Gefapixant for Refractory Atopic Cough: A Retrospective Cohort Study

Yoshihisa Ishiura,1,2 Shosaku Nomura,1,2 Noriyuki Ohkura,3 Johsuke Hara,3 Masaki Fujimura,3 Tomoki Ito1,2 1First Department of Internal Medicine, Kansai Medical University, Osaka, Japan; 2Respiratory Medicine, Kansai Medical University Medical Center, Osaka, Japan; 3Respiratory Medicine, Kanazawa University, Ishikawa, JapanCorrespondence: Yoshihisa Ishiura, First Department of Internal Medicine, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka, 570-8507, Japan, Tel +81 6 6992 1001, Fax +81 6 6992 1066, Email ishiura.yos@kmu.ac.jpBackground: Atopic cough, arising from hyperresponsiveness of afferent airway C-fibers, is common, and cough is one of the commonest reasons for referral to respiratory clinic. Gefapixant is a first-in-class P2X3 receptor antagonist recently approved for use in patients with refractory cough to inhibit airway C-fiber activation. We conducted this study to investigate the clinical effect of gefapixant in patients with refractory atopic cough that responded only partially to azelastine monotherapy.Methods: This was a single-center retrospective observational study. Patients with refractory atopic cough received gefapixant. Collected retrospectively from medical records, data included cough symptom questionnaire responses and results from respiratory function tests, cough reflex sensitivity tests, and blood tests.Results: Data from 23 patients with refractory atopic cough were included in this study. Spirometry parameters, fractional exhaled nitric oxide levels, peripheral eosinophil counts, and IgE levels were unchanged after gefapixant treatment. Scores for the cough severity visual analog scale and Leicester cough questionnaire significantly improved after treatment with gefapixant (both p< 0.01). Cough reflex sensitivity to inhaled capsaicin also significantly improved after treatment with gefapixant (p< 0.01).Conclusion: The P2X3 antagonist gefapixant appeared to improve patient-reported symptoms and cough reflex hypersensitivity in a retrospective cohort of patients with refractory atopic cough. These findings suggest P2X3 antagonists may be a treatment option for refractory atopic cough, possibly through possibly through reducing hypersensitivity of airway C fibers.Plain Language Summary: Cough is a frequent problem and one of the commonest reasons for referral to respiratory clinic. Atopic cough is a common cause of cough recognized widely in Japan, arisen from hyperresponsiveness of afferent airway C-fibers. Gefapixant is a newly generated P2X3 receptor antagonist for patients with refractory cough by reducing hypersensitivity of airway C fibers. Therefore, we conducted this study to investigate the clinical effect of gefapixant in patients with refractory atopic cough. As results, gefapixant significantly improves symptoms (p< 0.01) and cough reflex hypersensitivity (p< 0.01) in patients with refractory atopic cough. These findings indicate the potential of P2X3 antagonist for refractory atopic cough as one of the causes of refractory chronic cough (RCC) through reducing hypersensitivity of airway C fibers.