Department of Respiratory and Critical Care Medicine, School of Medicine and West China Hospital, Sichuan University, No.37 Guoxue Alley, Chengdu, 610041, West China, China.
Curr Allergy Asthma Rep. 2021 Aug 13;21(7):39. doi: 10.1007/s11882-021-01017-8.
Accumulating evidence has shown that prostaglandin D2 (PGD2)-chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) pathway plays an important role in promoting eosinophilic airway inflammation in asthma. We aimed to assess the efficacy and safety of CRTH2 antagonist fevipiprant in patients with persistent asthma compared with placebo.
We identified eligible studies by searching PubMed, EMBASE, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov. The study was registered as CRD 42020221714 ( http://www.crd.york.ac.uk/PROSPERO ). Ten randomized controlled trials with 7902 patients met our inclusion criteria. A statistically significant benefit of fevipiprant compared with placebo was shown in improving forced expiratory volume in 1 s (MD 0.05 L, 95% CI: 0.02 to 0.07; p < 0.0001), Asthma Control Questionnaire score (MD -0.10, 95% CI: -0.16 to -0.04; p = 0.001), and Asthma Quality of Life Questionnaire score (MD 0.08, 95% CI: 0.03 to 0.13; p = 0.003). Fevipiprant decreased number of patients with at least one asthma exacerbation requiring administration of systemic corticosteroids for 3 days or more (RR 0.86, 95% CI: 0.77 to 0.97; p = 0.01). Some benefits were a little more pronounced in the high eosinophil population (with an elevated blood eosinophil count or sputum eosinophil percentage) and in the 450 mg dose group. Fevipiprant was well tolerated with no safety issues compared with placebo. Fevipiprant could safely improve asthma outcomes compared to placebo. However, most of the differences didn't reach the minimal clinically important difference (MCID), thus the clinical benefits remained to be confirmed.
越来越多的证据表明,前列腺素 D2(PGD2)-嗜酸性粒细胞趋化因子受体同源分子表达在 Th2 细胞(CRTH2)通路中在促进哮喘中嗜酸性粒细胞气道炎症方面发挥重要作用。我们旨在评估 CRTH2 拮抗剂 fevipiprant 在持续性哮喘患者中的疗效和安全性,与安慰剂相比。
我们通过搜索 PubMed、EMBASE、Cochrane 中央对照试验注册库和 ClinicalTrials.gov 确定了合格的研究。该研究在 CRD 42020221714(http://www.crd.york.ac.uk/PROSPERO)上注册。10 项随机对照试验纳入了 7902 名患者,符合我们的纳入标准。与安慰剂相比,fevipiprant 显示出统计学上的显著益处,可改善用力呼气量 1 秒(MD 0.05 L,95%CI:0.02 至 0.07;p<0.0001)、哮喘控制问卷评分(MD-0.10,95%CI:-0.16 至 -0.04;p=0.001)和哮喘生活质量问卷评分(MD 0.08,95%CI:0.03 至 0.13;p=0.003)。fevipiprant 降低了至少一次需要全身皮质类固醇治疗 3 天或以上的哮喘加重患者的数量(RR 0.86,95%CI:0.77 至 0.97;p=0.01)。在高嗜酸性粒细胞人群(血液嗜酸性粒细胞计数或痰嗜酸性粒细胞百分比升高)和 450 mg 剂量组中,一些益处更为明显。与安慰剂相比,fevipiprant 具有良好的耐受性,没有安全性问题。与安慰剂相比,fevipiprant 可安全改善哮喘结局。然而,大多数差异没有达到最小临床重要差异(MCID),因此临床获益仍有待确认。