Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI.
Chemotherapy Center, Yokohama City University Hospital, Yokohama, Japan.
Chest. 2024 Nov;166(5):1124-1140. doi: 10.1016/j.chest.2024.05.015. Epub 2024 Jun 8.
Refractory or unexplained chronic cough disrupts quality of life and burdens health care systems around the world. The P2X3 receptor antagonist gefapixant is approved in many countries for its antitussive effects, but taste disturbances are a common adverse effect. Four newer, more selective P2X3 receptor antagonists have been developed to address this problem.
How does the benefit-risk profile vary across the five available P2X3 receptor antagonists?
A systematic review and network meta-analysis was conducted to evaluate the efficacy of P2X3 receptor antagonists, including gefapixant, sivopixant, eliapixant, camlipixant, and filapixant. Primary outcomes were a reduction rate in 24-hour cough frequency and incidence of taste disturbance. Dose-response curves and median effective dose (ED) were calculated. Effect size at ED was ranked according to the surface under the cumulative ranking curve. The confidence was evaluated by Confidence In Network Meta-Analysis.
Sixteen randomized controlled trials involving 4,904 participants were analyzed. The gefapixant regimen demonstrated an ED of 90.7 mg/d for cough frequency reduction. Gefapixant showed the highest antitussive effectiveness at ED (reduction rate in 24-hour cough frequency: median, 28.1%; 95% credible interval [CrI], 21.0%-35.6%; ranked 1 of 5; moderate certainty) but the highest prevalence of taste disturbance (absolute risk difference per 100 patients: median, 38; 95% CrI, 27-51; ranked 5 of 5; high certainty) and the highest prevalence of discontinuation. Camlipixant had a well-balanced profile (reduction rate in 24-hour cough frequency: median, 14.7%; 95% CrI, 5.4%-26.0%; ranked 3 of 5; low certainty; and taste disturbance; absolute risk difference per 100 patients; median, 2; 95% CrI, 1-6; ranked 2 of 5; low certainty). Placebo had a mean of 33.1% reduction in 24-hour cough frequency.
When used at safe doses, gefapixant had a favorable risk-benefit profile compared with the other four agents. Camlipixant showed initial promise, which may be further investigated by phase III trials currently underway.
University Hospital Medical Information Network Center (UMIN-CTR); No. UMIN000050622; URL: https://center6.umin.ac.jp.
难治性或不明原因的慢性咳嗽会扰乱生活质量，并给全球的医疗保健系统带来负担。P2X3 受体拮抗剂 gefapixant 在许多国家因其镇咳作用而获得批准，但味觉障碍是常见的不良反应。为了解决这个问题，已经开发出了四种更新、更具选择性的 P2X3 受体拮抗剂。
五种可用的 P2X3 受体拮抗剂的获益-风险特征如何变化？
进行了一项系统评价和网络荟萃分析，以评估 P2X3 受体拮抗剂（包括 gefapixant、sivopixant、eliapixant、camlipixant 和 filapixant）的疗效。主要结局是 24 小时咳嗽频率的降低率和味觉障碍的发生率。计算了剂量-反应曲线和中位有效剂量（ED）。根据累积排序曲线下面积对 ED 处的效应大小进行排名。置信度通过网络荟萃分析置信度评估。
分析了 16 项涉及 4904 名参与者的随机对照试验。Gefapixant 方案显示咳嗽频率降低的 ED 为 90.7mg/d。Gefapixant 在 ED 时表现出最高的镇咳效果（24 小时咳嗽频率降低率：中位数，28.1%；95%可信区间[CrI]，21.0%-35.6%；排名 1/5；中等确定性），但味觉障碍的发生率最高（每 100 例患者的绝对风险差异：中位数，38；95%CrI，27-51；排名 5/5；高确定性）和停药率最高。Camlipixant 具有良好的平衡特征（24 小时咳嗽频率降低率：中位数，14.7%；95%CrI，5.4%-26.0%；排名 3/5；低确定性；味觉障碍；每 100 例患者的绝对风险差异；中位数，2；95%CrI，1-6；排名 2/5；低确定性）。安慰剂组 24 小时咳嗽频率平均降低 33.1%。
当以安全剂量使用时，与其他四种药物相比，Gefapixant 的风险-效益特征有利。Camlipixant 显示出初步的希望，这可能会在目前正在进行的 III 期试验中进一步研究。
大学医院医疗信息网络中心（UMIN-CTR）；编号 UMIN000050622；网址：https://center6.umin.ac.jp。
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