Characterization of Patients With Refractory or Unexplained Chronic Cough Participating in a Phase 2 Clinical Trial of the P2X3-Receptor Antagonist Gefapixant

Abstract

Purpose: This analysis assesses clinical characteristics of patients with refractory chronic cough (RCC) or unexplained chronic cough (UCC) enrolled in a phase 2 study to better understand this patient population.

Methods: Patients with RCC/UCC lasting for ≥ 1 year and cough severity visual analog scale (VAS) score of > 40 mm at screening were eligible. Demographics, clinical characteristics, and medical history were collected at baseline. Cough-related measures included cough severity VAS, Cough Severity Diary (CSD), Leicester Cough Questionnaire (LCQ), and a structured cough-trigger questionnaire. Medication history included all medications 30 days before screening and chronic cough treatments within 1 year before screening. Data were summarized using descriptive statistics.

Results: Patients (N = 253; female, 76%; mean age, 60 years) had severe (mean cough severity VAS, 57.5 mm) and long-lasting (median duration, 11 years) cough. The most burdensome self-reported aspects included psychological and social factors (LCQ) and cough frequency and intensity (CSD). Patient-reported triggers were consistent with cough hypersensitivity (e.g., 95% to 96% reported irritation or tickle in throat). Common reported comorbidities included gastroesophageal reflux disease (GERD; 56%), allergic rhinitis (47%), and asthma (30%); 12% of patients had been diagnosed with all 3 conditions. The most common prior medications included inhaled or oral steroids (21%), antihistamines (15%), and antacids (15%).

Conclusion: Patients with RCC/UCC had severe, long-lasting, and burdensome cough with clinical features of cough hypersensitivity. Many patients had been diagnosed with GERD, allergic rhinitis, and asthma but had a persistent cough despite treatment of these conditions.

Trial registration: ClinicalTrials.gov, NCT02612610; registered November 20, 2015.

Keywords: Cough hypersensitivity syndrome; Idiopathic chronic cough; Persistent cough; Refractory cough; Troublesome cough.

Conflict of interest statement

AHM has received consulting fees from Bayer, Bellus, Boehringer Ingelheim, Merck, Pfizer, Proctor & Gamble, and Shionogi; lecture fees from AstraZeneca and Boehringer Ingelheim; and grant support from Afferent, Infirst, Merck, and Proctor & Gamble. SSB has received grants from Merck & Co., Inc.; scientific advisory board and consultancy fees from Bayer, Menlo, Merck & Co., Inc., Patara, Pfizer, and Sanofi; speaker fees from Roche; and grants for travel and subsistence for attendance to scientific meetings from Boehringer Ingelheim. JAS has received grants and personal fees related to the submitted work from Afferent Pharmaceuticals/Merck & Co., Inc.; grants from Ario Pharma, Bayer, Bellus, GlaxoSmithKline, Menlo, and NeRRe Pharmaceuticals; personal fees from Ario Pharma, Bayer, Bellus, Boehringer Ingleheim, Chiesi, GlaxoSmithKline, Genentech, Menlo, Neomed, and NeRRe Pharmaceuticals; nonfinancial support from Vitalograph; and is a named inventor on a patent, owned by Manchester University NHS Foundation Trust and licensed to Vitalograph Ltd, describing the detection of cough from sound recordings. JAS is also funded by the NIHR Manchester Biomedical Research Centre and a Wellcome Investigator Award and is an NIHR Senior Investigator. LPM has received grants from Afferent Pharmaceuticals/Merck & Co., Inc., British Heart Foundation, Chiesi, EU Interreg VA Health & Life Science Programme, and NC3Rs; personal fees from Afferent Pharmaceuticals/Merck & Co., Inc., Applied Clinical Intelligence, and AstraZeneca; grants for travel and subsistence for attendance to scientific meetings from Boehringer Ingelheim, Chiesi, and GlaxoSmithKline; and advisory board/consultancy fees from Almirall, Boehringer Ingelheim, GlaxoSmithKline, and NAPP. JS, AMN, ZJX, W-CW, and DRM are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. MRS has received grants and personal fees from Afferent Pharmaceuticals/Merck & Co., Inc. and is a consultant for AstraZeneca, Bayer, Bellus, NeRRe Therapeutics, and Nocion.

Figures

Fig. 1

Individual items in the Leicester Cough Questionnaire reported by patients at baseline. Data expressed in mean (95% confidence interval)

Fig. 2

Individual items in the Cough Severity Diary reported by patients at baseline. Data expressed in mean (95% confidence interval)

Fig. 3

Most common medical conditions associated with chronic cough in the patient population. a Percentage of patients with a medical history of GERD, asthma, or allergic rhinitis; b percentage of patients with a single diagnosis of GERD, asthma, or allergic rhinitis; and c percentage of patients with dual or all 3 diagnoses of GERD, asthma, or allergic rhinitis. GERD, gastroesophageal reflux disease. aDiagnostic codes in allergic rhinitis category include seasonal rhinitis, seasonal allergic rhinitis, seasonal allergies rhinitis, perennial seasonal allergic rhinitis (dust mite), and seasonal allergic rhinitis (trees weeds grass)