The following is a summary of “Benefit-Risk Profile of P2X3 Receptor Antagonists for Treatment of Chronic Cough: Dose-Response Model-Based Network Meta-Analysis,” published in the June 2024 issue of Pulmonology by Yamamoto et al.

Refractory or unexplained chronic cough significantly impacts patients’ quality of life and substantially burdens global healthcare systems. The P2X3 receptor antagonist gefapixant has been approved in numerous countries for its effectiveness in reducing cough, yet it is commonly associated with taste disturbances. Four newer, more selective P2X3 receptor antagonists—sivopixant, eliapixant, camlipixant, and filapixant—have been developed to address this issue. This study evaluated and compared the benefit-risk profiles of these five P2X3 receptor antagonists, including gefapixant.

A systematic review and network meta-analysis were performed, incorporating data from 16 randomized controlled trials with 4,904 participants. The primary outcomes assessed were reduced 24-hour cough frequency and the incidence of taste disturbances. Researchers calculated dose-response curves and the median effective dose (ED₅₀) for each drug and ranked the effect sizes using the surface under the cumulative ranking curve. The confidence in these findings was evaluated using Confidence In Network Meta-Analysis (CINeMA).

The results revealed that gefapixant, at an ED₅₀ of 90.7 mg/day, demonstrated the highest efficacy in reducing cough frequency, with a median reduction rate of 28.1% (95% credible interval [CrI], 21.0%-35.6%). However, it also exhibited the highest prevalence of taste disturbances, with an absolute risk difference per 100 patients of 38 (95% CrI, 27-51) and the highest discontinuation rate. In contrast, camlipixant presented a more balanced profile, with a median reduction rate in 24-hour cough frequency of 14.7% (95% CrI, 5.4%-26.0%) and a lower incidence of taste disturbances, with an absolute risk difference per 100 patients of 2 (95% CrI, 1-6). Placebo treatment resulted in a mean 33.1% reduction in cough frequency.

In conclusion, while gefapixant remains the most effective option for reducing cough frequency, it is also associated with significant taste disturbances. Camilpixant offers a more balanced benefit-risk profile, though it is less effective than gefapixant. These findings are crucial for guiding therapeutic decisions and optimizing treatment strategies for patients with chronic cough.

Source: sciencedirect.com/science/article/abs/pii/S0012369224006937