Exploring the Potential of a P2X3 Receptor Antagonist: Gefapixant in the Management of Persistent Cough Associated with Interstitial Lung Disease.

Background: Interstitial lung disease (ILD) is characterized by pulmonary inflammation and fibrosis associated with persistent and refractory cough that significantly hinders quality of life. Conventional treatments for ILD-associated cough have shown limited efficacy, necessitating alternative therapeutic approaches. Gefapixant, a P2X3 receptor antagonist, can potentially alleviate chronic cough by inhibiting the ATP-mediated activation of sensory C-fibers, but its efficacy in ILD-associated cough remains unclear. This study observed the effects of gefapixant on ILD-associated refractory chronic cough. Methods: This prospective study enrolled patients with ILD-associated refractory chronic cough who received gefapixant at Sapporo Medical University Hospital between July 2022 and November 2023. Cough frequency, Leicester Cough Questionnaire (LCQ) score, cough severity visual analog scale (Cough VAS), and taste VAS were evaluated at baseline and at 2, 4, and 8 weeks after gefapixant administration. Results: Six patients completed the study. Their ILD subtypes included idiopathic pulmonary fibrosis (IPF), nonspecific interstitial pneumonia (NSIP), and connective tissue disease-associated ILDs (CTD-ILDs). After 8 weeks, the cough frequency decreased from 88.5 to 44.3 episodes per 30 min, LCQ scores increased from 8.3 to 13.6, and cough VAS scores decreased from 75.8 to 40.2. However, statistical significance was not reached due to high interindividual variability, with gefapixant being effective in some and ineffective in others. The most common adverse event was taste disorder, leading to discontinuation in one patient, but symptoms tended to lessen over the course of treatment. Conclusions: Gefapixant appears to be effective in reducing refractory cough related to ILD, although these results were not statistically significant because its effectivity widely varied across individuals. Further investigation is needed to identify patient subgroups with the greatest potential for treatment responsiveness.