Clinical characteristics associated with limited response to gefapixant in refractory chronic cough

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Background: Gefapixant provides effective or marked improvement within 4 weeks in over half of patients with refractory chronic cough (RCC), yet some discontinue treatment due to limited benefit. Identifying clinical characteristics in discontinuation cases may inform future research and management. Methods: We analyzed data from a retrospective Japanese Cough Society study of RCC patients prescribed gefapixant. We focused on cases in which gefapixant was discontinued and post-discontinuation cough severity (0–10 scale; 10 worst) was recorded. Patients were classified into three groups: rapid-onset responders (effective or better within 4 weeks), slow-onset responders (less than effective within 4 weeks but cough ≤5 after discontinuation), and non-responders (cough >5). Results: Among 109 cases, 39 were rapid-onset, 35 slow-onset, and 35 non-responders. Compared with the rapid-onset group, both the slow-onset and non-response groups had longer cough duration, visited more healthcare facilities, showed fewer cases of asthmatic cough, post–COVID-19 cough, or laryngeal discomfort, and had more cough associated with indigestion. The slow-onset group had a lower BMI than non-responders, had the mildest baseline cough severity, and showed intermediate cough suppression before and after gefapixant between rapid-onset responders and non-responders. Age, sex, duration of administration, time since discontinuation, and taste disturbance severity were similar across groups. Conclusion: In patients with long-standing RCC, even with mild laryngeal discomfort, gradual cough suppression may occur after gefapixant when baseline cough severity is relatively mild. Further studies are needed to clarify the characteristics of gefapixant non-responders.

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