Study examines efficacy and tolerability of emerging cough suppressant gefapixant

Health Canada has not yet approved any treatments for refractory or unexplained chronic cough. Clinical guidelines recommend treatment with speech pathology or neuromodulators, such as morphine, gabapentin, pregabalin or amitriptyline. However, these therapies have dose-limiting adverse effects, are ineffective in some patients, and may be unsuitable for long-term use.1 P2X3 antagonists are a new class of antitussives for refractory or unexplained chronic cough. They block the P2X3 receptor (an adenosine triphosphate–gated ion channel on chemically sensitive airway C-fibres), which reduces the activation of C-fibres that transmit action potentials to the brainstem and somatosensory cortex that control cough.1 Gefapixant is not yet approved for use in Canada or the United States; however, it is under regulatory consideration in these and other countries as a treatment for refractory or unexplained chronic cough. Although individual clinical trials have highlighted the efficacy of P2X3 antagonism for treatment of refractory or unexplained chronic cough, no studies have yet evaluated all randomized trial evidence on gefapixant. Such information would help to inform regulatory agencies, guideline developers, payers, clinicians and patients regarding the magnitude of the drug’s benefit and its tolerability.1 To shed light on this issue, researchers undertook a systematic review and dose-response meta-analysis to evaluate the efficacy and tolerability of gefapixant in patients with refractory or unexplained chronic cough.1 The main outcomes measured were cough frequency, cough severity, cough-specific quality of life, treatment-related adverse events, adverse events leading to discontinuation and taste-related adverse events.1 Results showed the following: The primary analysis included nine randomized controlled trials, with a total of 2,980 patients. Compared with placebo, gefapixant (45 mg twice daily) had small effects on awake cough frequency (17.6% reduction [95%CI, 10.6%–24.0%]; moderate certainty), cough severity on the 100-mm visual analog scale (mean difference, −6.2mm [95%CI, −4.1 to −8.4]; high certainty), and cough-specific quality of life on the Leicester Cough Questionnaire (mean difference, 1.0 points [95%CI, 0.7–1.4]; moderate certainty). Compared with placebo, gefapixant (45 mg twice daily) probably caused an important increase in treatment-related adverse events (32 more per 100 patients [95%CI, 13–64 more]; moderate certainty) and taste-related adverse events (32 more per 100 patients [95%CI, 22–46 more], high certainty). Compared with placebo, gefapixant (15 mg twice daily) had small effects on taste-related adverse events (6 more per 100 patients [95%CI, 5–8 more]; high certainty). Compared with placebo, gefapixant (45 mg twice daily) caused an important increase in adverse events leading to discontinuation (RR, 4.3 [95% CI, 3.2–5.8]; moderate certainty).1 The authors conclude that compared with placebo, gefapixant (45 mg orally twice daily) led to modest improvements in cough frequency, cough severity and cough-specific quality of life. It also reduced cough frequency by 17.6%, decreased cough severity by 6.2 mm on the 100-mm visual analog scale, and improved cough quality of life by 1 point on the Leicester Cough Questionnaire (score range, 3-21). Patients treated with gefapixant (45 mg twice daily) had a 32% increase in taste-related adverse events compared with placebo. The authors maintain that although gefapixant may provide benefit to some patients with refractory or unexplained chronic cough, the magnitude of benefit is likely small and the risk of taste-related adverse events is increased.1 Reference 1. Kum E, Patel M, Diab N, et al. Efficacy and tolerability of gefapixant for treatment of refractory or unexplained chronic cough. A systematic review and dose-response meta-analysis. JAMA 2023; Published online September 11, 2023. (accessed September 12, 2023).

Study examines efficacy and tolerability of emerging cough suppressant gefapixant

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