Efficacy and Safety of varying dosage of Gefapixant in Patients with chronic cough. A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background A cough that remains unresolved for longer than 8 weeks is referred to as chronic cough, and it is estimated that 10% of the adult population of the world suffers from chronic cough. Gefapixant is a purinergic receptor P2x3 receptor antagonist. P2x3 receptors are ATP-gated ion channels on the peripheral sensory C fibers in the airways. Objective We conducted a systematic review and meta-analysis of RCTs to investigate whether the chronic cough patients would benefit from gefapixant administration or not when compared to placebo. Methods We selected only those double-arm randomized controlled trials (RCTs) which included participants presenting with a chronic cough in patients 18 years or older. We excluded all the articles published in languages other than English Language. Furthermore, all the studies other than RCTs were also omitted. Articles yielded from the electronic search were exported to EndNote Reference Library software to remove any duplicates. Analyses were done using the Review Manager 5.4 tool. Mean values and standard deviations were retrieved for the continuous outcomes given as raw data. Results 8 RCTs selected for the statistical analysis consisted of 2024 participants (1011 in the intervention group and 1013 in the placebo group). The outcomes resulted to be significant with 24-hour cough frequency, the mean difference [MD] = -5.26, 95% confidence interval [CI] -7.18 to -3.33; p = 0.00001; n = 3518, awake cough frequency (c/h) [MD] = -6.78, 95% confidence interval [CI] -9.46 to -4.09; p = 0.00001; n = 3472 patients., night cough frequency (c/h) [MD] = -4.07, 95% confidence interval [CI] -5.49 to -2.65; p = 0.00001; n = 479, patients cough severity VAS (mm) [MD] = -14.84, 95% confidence interval [-19.92, -9.76], p = 0.00001, n= 1297, cough severity diary difference [MD] = -0.85; 95% confidence interval [CI]: -1.14, -0.56; p-value = 0.00001; n = 1219, Total LCQ score MD=2.04, 95% CI = 1.09 to 2.98, p<0.0001, n =869. Conclusion To conclude, the lowest efficacious dose was 50 mg twice daily and helped reduce 24-hour cough frequency, awake cough frequency, night cough frequency, and cough severity using VAS in a dose-dependent manner. Gefapixant showed a significant risk of adverse events which include dysgeusia, hypogeusia, nausea, any adverse event, taste-related and drug-related adverse events, and serious AEs