Dupilumab减少糖皮质激素依赖严重哮喘患者口服糖皮质激素的使用:一项3期、开放性扩展TRAVERSE试验的研究
2022/03/17
摘要
背景：许多严重哮喘患者需要皮质类固醇(OCS)来维持哮喘的控制。严重OCS依赖性哮喘患者口服OCS使用减少和dupilumab治疗观察到的临床疗效是否能长期维持?
方法：TRAVERSE (NCT02134028)是一项跨国、多中心、单臂、开放性扩展研究，研究对象为年龄≥12岁、参与dupilumab既往研究的哮喘患者。治疗包括dupilumab, 300mg，每2周，持续96周。在这项分析中，我们展示了最初加入VENTURE (NCT02528214)的患者的数据，这是一项为期24周的dupilumab安慰剂对照研究，用于OCS依赖的严重哮喘患者，并继续在TRAVERSE进行研究。分析的亚组是:dupilumab/dupilumab(两组均为dupilumab)和安慰剂/dupilumab(安慰剂在VENTURE, dupilumab在TRAVERSE)。结果包括OCS的使用，加重率，肺功能和哮喘控制的措施。
结果：90名dupilumab/dupilumab和97名安慰剂/dupilumab VENTURE患者入组并接受TRAVERSE治疗，在VENTURE研究基线时，平均OCS剂量为11.0 (dupilumab)和11.6mg/天(安慰剂)。在TRAVERSE 第0周,平均每日口服剂量为3.1和6.4毫克/天(百分比减少风险基准68.8%和41.3%)，dupilumab / dupilumab和安慰剂/ dupilumab在48周分别下降到2.2和4.9毫克/天(78.3%和53.4%)，在96周分别下降到1.2和3.0毫克/天(89.3%和74.4%)。在TRAVERSE期间加重率很低。从VENTURE到TRAVERSE，在1秒用力呼气量和5项哮喘控制问卷得分上也有进一步的改善。安全性发现与已知的dupilumab安全性特征一致。
结论：在开放性扩展TRAVERSE研究中，dupilumab证明了其维持原OCS-sparing研究中OCS剂量减少的能力，同时保持低加重率和改善肺功能.
Dupilumab reduces oral corticosteroid use in patients with corticosteroid-dependent severe asthma: An analysis of the phase 3, open-label extension TRAVERSE trial
Sher LD, Wechsler ME, Rabe KF, et al
Abstract
BACKGROUND:Many patients with severe asthma require chronic corticosteroids to maintain asthma control. Are the reduction in oral corticosteroid (OCS) use and the clinical efficacy observed with dupilumab treatment maintained long-term in patients with severe OCS-dependent asthma?
METHODS:TRAVERSE (NCT02134028) was a multinational, multicenter, single-arm, open-label extension study in patients aged ≥12 years with asthma who participated in previous dupilumab studies. Treatment consisted of dupilumab 300mg every 2 weeks for up to 96 weeks. In this analysis, we present the data from patients who initially enrolled in VENTURE (NCT02528214), a 24-week placebo-controlled study of dupilumab in patients with OCS-dependent severe asthma, and continued in TRAVERSE. The subgroups analyzed were: dupilumab/dupilumab (dupilumab in both) and placebo/dupilumab (placebo in VENTURE and dupilumab in TRAVERSE). Outcomes included OCS use, exacerbation rates and measures of lung function and asthma control.
RESULTS:90 dupilumab/dupilumab and 97 placebo/dupilumab VENTURE patients were enrolled and treated in TRAVERSE, with a mean OCS dose of 11.0 (dupilumab) and 11.6mg/day (placebo) at VENTURE study baseline. At TRAVERSE Week 0, the mean daily OCS dose was 3.1 and 6.4mg/day (percentage decrease from VENTURE baseline 68.8% and 41.3%) for dupilumab/dupilumab and placebo/dupilumab, respectively, and decreased to 2.2 and 4.9mg/day (78.3% and 53.4%) at Week 48 and to 1.2 and 3.0mg/day (89.3% and 74.4%) at Week 96. Exacerbation rates were low during TRAVERSE. Further improvements from VENTURE to TRAVERSE were also seen in forced expiratory volume in 1 second and 5- item Asthma Control Questionnaire scores. Safety findings were consistent with the known dupilumab safety profile.
CONCLUSIONS:In the open-label TRAVERSE study, dupilumab demonstrated the ability to sustain the OCS dose reduction from the parent OCS-sparing study, while maintaining a low exacerbation rate and improved lung function.
背景：许多严重哮喘患者需要皮质类固醇(OCS)来维持哮喘的控制。严重OCS依赖性哮喘患者口服OCS使用减少和dupilumab治疗观察到的临床疗效是否能长期维持?
方法：TRAVERSE (NCT02134028)是一项跨国、多中心、单臂、开放性扩展研究，研究对象为年龄≥12岁、参与dupilumab既往研究的哮喘患者。治疗包括dupilumab, 300mg，每2周，持续96周。在这项分析中，我们展示了最初加入VENTURE (NCT02528214)的患者的数据，这是一项为期24周的dupilumab安慰剂对照研究，用于OCS依赖的严重哮喘患者，并继续在TRAVERSE进行研究。分析的亚组是:dupilumab/dupilumab(两组均为dupilumab)和安慰剂/dupilumab(安慰剂在VENTURE, dupilumab在TRAVERSE)。结果包括OCS的使用，加重率，肺功能和哮喘控制的措施。
结果：90名dupilumab/dupilumab和97名安慰剂/dupilumab VENTURE患者入组并接受TRAVERSE治疗，在VENTURE研究基线时，平均OCS剂量为11.0 (dupilumab)和11.6mg/天(安慰剂)。在TRAVERSE 第0周,平均每日口服剂量为3.1和6.4毫克/天(百分比减少风险基准68.8%和41.3%)，dupilumab / dupilumab和安慰剂/ dupilumab在48周分别下降到2.2和4.9毫克/天(78.3%和53.4%)，在96周分别下降到1.2和3.0毫克/天(89.3%和74.4%)。在TRAVERSE期间加重率很低。从VENTURE到TRAVERSE，在1秒用力呼气量和5项哮喘控制问卷得分上也有进一步的改善。安全性发现与已知的dupilumab安全性特征一致。
结论：在开放性扩展TRAVERSE研究中，dupilumab证明了其维持原OCS-sparing研究中OCS剂量减少的能力，同时保持低加重率和改善肺功能.
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（Chest. 2022 Feb 22;S0012-3692(22)00388-9. doi: 10.1016/j.chest.2022.01.071.）
（Chest. 2022 Feb 22;S0012-3692(22)00388-9. doi: 10.1016/j.chest.2022.01.071.）
Dupilumab reduces oral corticosteroid use in patients with corticosteroid-dependent severe asthma: An analysis of the phase 3, open-label extension TRAVERSE trial
Sher LD, Wechsler ME, Rabe KF, et al
Abstract
BACKGROUND:Many patients with severe asthma require chronic corticosteroids to maintain asthma control. Are the reduction in oral corticosteroid (OCS) use and the clinical efficacy observed with dupilumab treatment maintained long-term in patients with severe OCS-dependent asthma?
METHODS:TRAVERSE (NCT02134028) was a multinational, multicenter, single-arm, open-label extension study in patients aged ≥12 years with asthma who participated in previous dupilumab studies. Treatment consisted of dupilumab 300mg every 2 weeks for up to 96 weeks. In this analysis, we present the data from patients who initially enrolled in VENTURE (NCT02528214), a 24-week placebo-controlled study of dupilumab in patients with OCS-dependent severe asthma, and continued in TRAVERSE. The subgroups analyzed were: dupilumab/dupilumab (dupilumab in both) and placebo/dupilumab (placebo in VENTURE and dupilumab in TRAVERSE). Outcomes included OCS use, exacerbation rates and measures of lung function and asthma control.
RESULTS:90 dupilumab/dupilumab and 97 placebo/dupilumab VENTURE patients were enrolled and treated in TRAVERSE, with a mean OCS dose of 11.0 (dupilumab) and 11.6mg/day (placebo) at VENTURE study baseline. At TRAVERSE Week 0, the mean daily OCS dose was 3.1 and 6.4mg/day (percentage decrease from VENTURE baseline 68.8% and 41.3%) for dupilumab/dupilumab and placebo/dupilumab, respectively, and decreased to 2.2 and 4.9mg/day (78.3% and 53.4%) at Week 48 and to 1.2 and 3.0mg/day (89.3% and 74.4%) at Week 96. Exacerbation rates were low during TRAVERSE. Further improvements from VENTURE to TRAVERSE were also seen in forced expiratory volume in 1 second and 5- item Asthma Control Questionnaire scores. Safety findings were consistent with the known dupilumab safety profile.
CONCLUSIONS:In the open-label TRAVERSE study, dupilumab demonstrated the ability to sustain the OCS dose reduction from the parent OCS-sparing study, while maintaining a low exacerbation rate and improved lung function.
上一篇：
使用呼出型一氧化氮(RAACENO)作为生物标志物来减少儿童哮喘发作，为治疗策略提供信息:一项多中心、平行、随机、对照、
下一篇：
在轻度间歇性（1级）哮喘患儿中按需单独使用短效β2受体激动剂与按需使用短效β2受体激动剂加吸入性皮质类固醇：一项成本效益
