The Cough Severity Diary in a pooled analysis of two, phase 3 trials of gefapixant in chronic cough

Objective: We evaluated the impact of gefapixant, a P2X3 receptor antagonist, on patient-reported cough severity over 52 weeks in patients with refractory or unexplained chronic cough (RCC or UCC). Methods: COUGH-1 (NCT03449134) and COUGH-2 (NCT03449147) were 52-wk, RCTs of gefapixant 15 mg and 45 mg BID, and placebo in RCC or UCC patients (≥18 yrs old, chronic cough ≥1 yr duration, screening/baseline cough severity VAS ≥40 mm). The Cough Severity Diary (CSD) is a 7-item PRO assessing domains of frequency, intensity, and disruption due to cough; items rated 0-10. The proportion with clinically meaningful (≥1.3-point or ≥2.7-point) reduction from baseline in mean weekly CSD total score was evaluated using a logistic regression model. Results: A greater proportion of participants treated with gefapixant achieved meaningful CSD total score improvements at all timepoints. At Week 52, 76% of patients in the gefapixant 45 mg group were responders based on the ≥1.3-point threshold. Greater dose response and separation of the gefapixant 45mg group from placebo at Week 52 was observed with the 2.7-point vs. 1.3-point threshold. (Figure) Conclusions: Treatment with gefapixant 45 mg BID resulted in a greater proportion of chronic cough patients reporting meaningful improvements in cough frequency, intensity, and disruption due to cough vs. placebo over 52 weeks, particularly with the more stringent CSD threshold. Figure: