Peninsula Research Associates, Rolling Hills Estates, CA.
National Jewish Health, The NJH Cohen Family Asthma Institute, Denver, CO.
Chest. 2022 Jul;162(1):46-55. doi: 10.1016/j.chest.2022.01.071. Epub 2022 Feb 22.
Many patients with severe asthma require chronic corticosteroid treatment 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?
The LIBERTY ASTHMA TRAVERSE study (ClinicalTrials.gov identifier: NCT02134028) was a multinational, multicenter, single-arm, open-label extension study in patients ≥ 12 years of age with asthma who participated in previous dupilumab studies. Treatment consisted of dupilumab 300 mg every 2 weeks for up to 96 weeks. In this analysis, we present the data from patients who initially enrolled in the LIBERTY ASTHMA VENTURE study (ClinicalTrials.gov identifier: NCT02528214), a 24-week placebo-controlled study of dupilumab in patients with OCS-dependent severe asthma, and continued in the TRAVERSE study. The subgroups analyzed were: those who received dupilumab in both (dupilumab/dupilumab group) and those who received placebo in the VENTURE study and dupilumab in the TRAVERSE study (placebo/dupilumab group). Outcomes included OCS use, exacerbation rates, and measures of lung function and asthma control.
Ninety patients treated with dupilumab/dupilumab and 97 patients treated with placebo/dupilumab in the VENTURE study were enrolled and treated in the TRAVERSE study, with a mean OCS dosage of 11.0 mg/d (dupilumab) and 11.6 mg/d (placebo) at VENTURE study baseline. At TRAVERSE week 0, the mean daily OCS dosage was 3.1 mg/d and 6.4 mg/d (percentage decrease from the VENTURE study baseline, 68.8% and 41.3%) for the dupilumab/dupilumab group and placebo/dupilumab group, respectively, and decreased to 2.2 mg/d and 4.9 mg/d (78.3% and 53.4%) at week 48 and to 1.2 mg/d and 3.0 mg/d (89.3% and 74.4%) at week 96, respectively. Exacerbation rates were low during the TRAVERSE study. Further improvements from the VENTURE to TRAVERSE studies also were seen in FEV and 5-item Asthma Control Questionnaire scores. Safety findings were consistent with the known dupilumab safety profile.
In the open-label TRAVERSE study, dupilumab demonstrated the ability to sustain the OCS dosage reduction from the parent OCS-sparing study, while maintaining a low exacerbation rate and improved lung function.
ClinicalTrials.gov; Nos.: NCT02134028 (TRAVERSE) and NCT02528214 (VENTURE); URL: www.
gov.
许多严重哮喘患者需要长期使用皮质类固醇药物（OCS）以控制哮喘。
在严重依赖 OCS 的哮喘患者中，使用度普利尤单抗治疗后 OCS 用量减少和临床疗效是否能长期维持？
LIBERTY ASTHMA TRAVERSE 研究（ClinicalTrials.gov 标识符：NCT02134028）是一项多中心、多国、单臂、开放标签的扩展研究，纳入了≥12 岁、曾参加过度普利尤单抗研究的哮喘患者。治疗方案为每 2 周接受 300mg 度普利尤单抗治疗，最长可达 96 周。在本分析中，我们报告了最初参加 LIBERTY ASTHMA VENTURE 研究（ClinicalTrials.gov 标识符：NCT02528214）的患者的数据，这是一项为期 24 周的安慰剂对照研究，评估了度普利尤单抗在 OCS 依赖型严重哮喘患者中的疗效，这些患者继续参加了 TRAVERSE 研究。分析的亚组包括：在 VENTURE 研究中接受度普利尤单抗治疗（度普利尤单抗/度普利尤单抗组）和在 VENTURE 研究中接受安慰剂治疗、在 TRAVERSE 研究中接受度普利尤单抗治疗（安慰剂/度普利尤单抗组）的患者。主要结局包括 OCS 使用情况、哮喘恶化率以及肺功能和哮喘控制的衡量指标。
在 VENTURE 研究中接受度普利尤单抗/度普利尤单抗治疗和安慰剂/度普利尤单抗治疗的 90 名和 97 名患者分别入组并参加了 TRAVERSE 研究，在 VENTURE 研究基线时，他们的 OCS 剂量均值分别为 11.0mg/d（度普利尤单抗）和 11.6mg/d（安慰剂）。在 TRAVERSE 研究第 0 周，度普利尤单抗/度普利尤单抗组和安慰剂/度普利尤单抗组的每日 OCS 剂量分别为 3.1mg/d 和 6.4mg/d（与 VENTURE 研究基线相比的降幅分别为 68.8%和 41.3%），在第 48 周降至 2.2mg/d 和 4.9mg/d（降幅分别为 78.3%和 53.4%），在第 96 周降至 1.2mg/d 和 3.0mg/d（降幅分别为 89.3%和 74.4%）。在 TRAVERSE 研究期间，哮喘恶化率较低。与 VENTURE 研究相比，在 TRAVERSE 研究中也观察到 FEV1 和 5 项哮喘控制问卷评分的进一步改善。安全性发现与度普利尤单抗已知的安全性特征一致。
在开放标签的 TRAVERSE 研究中，度普利尤单抗能够维持来自母体 OCS 节约研究的 OCS 剂量减少，同时保持低哮喘恶化率和改善肺功能。
ClinicalTrials.gov；编号：NCT02134028（TRAVERSE）和 NCT02528214（VENTURE）；网址：www.clinicaltrials.gov。
