慢性鼻窦炎伴鼻息肉(CRSwNP)与哮喘有关,尤其是晚期发作。目前CRSwNP的治疗方案有局限性,对其他安全有效的疗法的需求尚未得到满足。
THUNDER研究的目的是确定前列腺素D2受体2(DP2)拮抗剂feviprant在CRSwNP和合并哮喘患者中的疗效和安全性。通过改善鼻息肉评分(主要终点)来衡量,鼻塞评分,鼻窦结果测试22分,和宾夕法尼亚大学气味鉴定测试成绩。
雷声是3b阶段,随机化,多中心,双盲,安慰剂对照,平行组,feviprant150mg或450mg每日一次与安慰剂的16周研究。所有患者每天200μg鼻内接受糠酸莫米松。
98例患者被随机分配到feviprant150mg(n=32),fevipiprant450毫克(n=34),或安慰剂(n=32)。对于feviprant150mg,第16周鼻息肉评分相对于基线的平均(SE)变化为0.20(0.224),对于feviprant450mg,-0.10(0.216),安慰剂为0.14(0.233)。平均治疗差异为0.05(95%置信区间,-0.59,0.70;调整后的P=.979)对于feviprant150mg与安慰剂和-0.25(95%置信区间,-0.88,0.39;调整后的P=.656)对于feviprant450mg与安慰剂。feviprant与安慰剂的次要终点没有有意义的差异。
THUNDER没有提供任何证据证明fevipiprant在治疗CRSwNP和哮喘患者中的作用;未来的研究可能会确立其他DP2拮抗剂的作用,特别是阿司匹林加重的呼吸系统疾病患者。
Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with asthma, particularly of late onset. Current treatment options for CRSwNP have limitations, and there is an unmet need for other safe and effective therapies.
The aim of the THUNDER study was to determine the efficacy and safety of the prostaglandin D2 receptor 2 (DP2) antagonist fevipiprant in patients with CRSwNP and concomitant asthma, measured by improvement in nasal polyp score (primary end point), nasal congestion score, Sinonasal Outcome Test 22 score, and University of Pennsylvania Smell Identification Test score.
THUNDER was a phase 3b, randomized, multicenter, double-blind, placebo-controlled, parallel-group, 16-week study of fevipiprant 150 mg or 450 mg once daily versus placebo. All patients received intranasal mometasone furoate 200 μg daily.
Ninety-eight patients were randomly assigned to
fevipiprant 150 mg (n = 32),
fevipiprant 450 mg (n = 34), or placebo (n = 32). Mean (SE) change from baseline in nasal polyp score at week 16 was 0.20 (0.224) for
fevipiprant 150 mg, -0.10 (0.216) for
fevipiprant 450 mg, and 0.14 (0.233) for placebo. Mean treatment difference was 0.05 (95% confidence interval, -0.59, 0.70; adjusted P = .979) for fevipiprant 150 mg versus placebo and -0.25 (95% confidence interval, -0.88, 0.39; adjusted P = .656) for fevipiprant 450 mg versus placebo. There was no meaningful difference in the secondary end points for
fevipiprant versus placebo.
THUNDER provided no evidence of a role for
fevipiprant in the treatment of patients with CRSwNP and asthma; future studies may establish a role for other DP2 antagonists, specifically in patients with aspirin-exacerbated respiratory disease.