Comparisons Of Baseline Characteristics And Treatment Efficacy In Individuals With Refractory Or Unexplained Chronic Cough Enrolled In Phase 3 Trials Of Gefapixant

Chronic cough (CC) that persists despite investigation and treatment has been described as refractory CC (RCC; cough persisting despite treatment of presumed contributing comorbidities) and unexplained CC (UCC; cough nonsuggestive of contributory comorbidities despite clinical evaluation). These terms help identify comorbid conditions and permit subgroup comparisons of patients with vs without comorbidities. Herein, pooled data from two gefapixant phase 3 trials evaluated subgroups of patients with RCC vs UCC. COUGH-1 and COUGH-2 enrolled adults with CC ≥1 year, guidelines-based diagnosis of RCC or UCC (determined by enrolling physician), and cough severity ≥40 mm/100-mm visual analog scale. Baseline characteristics are reported for RCC and UCC subgroups. Efficacy (24-hour and awake cough frequency at Week 12) was assessed via longitudinal ANCOVA and is reported as estimated relative reductions from baseline vs placebo. Of 1360 participants receiving placebo or gefapixant 45 mg BID, 844 (62%) and 516 (38%) were categorized as RCC or UCC, respectively. Similar proportions were female (RCC, 76%; UCC, 73%) and aged ≥60 years (RCC, 54%; UCC, 49%). Mean cough duration was 11 years (for both). In both subgroups, treatment with gefapixant 45 mg reduced placebo-adjusted 24-hour cough frequency (estimated relative reduction [95% CI]: RCC, -16% [-26%, -4%]; UCC, -22% [-36%, -5%]) and awake cough frequency (RCC, -16% [-26%, -4%]; UCC, -19% [-34%, -1%]). In a guidelines-diagnosed population, patients with RCC or UCC had similar clinical features and experienced consistent cough frequency reductions with gefapixant. Although RCC and UCC may share underlying pathophysiology, additional data are needed to inform terminology.