Patients taking gefapixant 45 mg for refractory/unexplained chronic cough (RCC/UCC) had a high likelihood of reporting a clinically meaningful improvement in outcomes that was maintained for 52 weeks, according to a research letter published in the American Journal of Respiratory and Critical Care Medicine.
Researchers sought to explore the durability of gefapixant 45 mg twice daily for treatment of refactory/unexplained chronic cough through analysis of patient-reported outcome (PRO) data from the COUGH-1 and -2 trials (ClinicalTrials.gov Identifiers: NCT03449134 and NCT03449147, respectively) evaluating the benefit and safety of gefapixant over a 1-year period.
In the clinical trials, gefapixant 45 mg was associated with statistically significant improvement in refractory/unexplained chronic cough vs placebo (whereas gefapixant 15 mg was not). The research letter authors therefore analyzed PROs obtained through week 52 for gefapixant 45 mg vs placebo. These PROs included the Leicester Cough Questionnaire (LCQ), cough severity visual analog scale (VAS), and Cough Severity Diary (CSD). Efficacy was assessed with least-squares (LS) means over time and responder analyses with use of definitions of clinically meaningful improvement at weeks 12, 24, and 52.
Adverse events (AEs) were evaluated at screening, baseline, and randomization, every 4 weeks until week 24, and then every 7 weeks thereafter. Taste-related AEs including dysgeusia, ageusia, hypogeusia, or related terms were prespecified for analysis. Post-hoc analyses were performed for discontinuation due to a taste-related AE, time to discontinuation due to a taste-related AE, and time to resolution of taste-related AEs.
The pooled population included 2044 participants in 3 treatment arms, of whom 1631 continued in the extension periods and 1534 completed 52 weeks of treatment. The participants were primarily female (75%) and White (80%), and their mean cough duration was 11.3 years. A total of 683 participants were treated with gefapixant 45 mg BID, and 675 participants received placebo.
Least-squares mean PROs in the placebo and gefapixant groups improved during the 52 weeks, with greater improvement occurring for those who received gefapixant 45 mg twice daily vs placebo. For each PRO, the odds of having a clinically meaningful response were improved for gefapixant 45 mg vs placebo at each time point.
At week 52, odds ratios in favor of gefapixant were 1.72 (95% CI, 1.31, 2.27) for an LCQ showing improvement of at least 1.3 points; 1.47 (95% CI, 1.15, 1.89) for a VAS showing at least a 30 mm improvement; 1.62 (95% CI, 1.23, 2.15) for a CSD showing at least a 1.3-point improvement; and 1.57 (95% CI, 1.21, 2.03) for a CSD showing at least a 2.7-point improvement.
A higher proportion of participants had at least 1 taste-related AE in the gefapixant 45-mg twice daily arm (65.4%) vs the placebo arm (7.0%) at week 52. In addition, a higher proportion of participants discontinued owing to a taste-related AE in the gefapixant group (13.9%) vs the placebo arm (0.3%). Half of the discontinuations due to taste-related AEs in the gefapixant group occurred in the initial 4 weeks of treatment.
In an analysis of follow-up data collected after the database lock in December 2021, 7 of the 683 participants using gefapixant had unresolved taste-related AEs, compared with 6 of 675 participants in the placebo group.
“These data indicate that gefapixant may be an important, durable treatment for refractory chronic cough or unexplained chronic cough, which are long-lasting conditions with a significant unmet need for safe and effective treatments,” the authors of the research letter concluded.
Disclosure: Funding for this research was provided by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc. Please see the original reference for a full list of disclosures.
Birring SS, Dicpinigaitis PV, Smith JA, et al. Efficacy and safety of gefapixant for refractory or unexplained chronic cough over 52 weeks. Am J Respir Crit Care Med. Published online March 30, 2023. doi:10.1164/rccm.202211-2128LE