度普利尤单抗治疗哮喘儿童的长期安全性及有效性评估（自由哮喘研究）：一项开放标签扩展研究
2024/03/26
摘要
背景：VOYGE研究为期52周，是一项多国、多中心、3期随机、双盲、安慰剂对照试验。该研究证实了度普利尤单抗对6-11岁罹患未控制中重度哮喘儿童的有效性和安全性。
目的：本研究旨在评估度普利尤单抗对曾参与VOYAGE研究的中重度哮喘患儿的长期安全性和有效性。
方法：EXCURSION研究是一项为期52周的开放标签扩展研究，共纳入365名VOYAGE研究中的中重度哮喘患儿（共408名），在17个国家、70个中心开展。其中，度普利尤单抗/度普利尤单抗组的240名患儿继续每2周皮下注射一次度普利尤单抗（根据体重给药：在EXCURSION基线时体重≤30 kg的患儿为100 mg，体重＞30 kg的患儿为200 mg）；安慰剂/度普利尤单抗组的125名患儿在VOYAGE研究期间应用安慰剂，在本研究中启动度普利尤单抗（根据体重用量100或200 mg），每2周皮下注射一次。研究方案修订后，对于体重≤30公斤的患儿亚组，用量调整为每4周一次，每次300毫克。开放标签扩展研究的主要终点为在52周的研究期间，在总人群（定义为6-11岁患有中重度哮喘且先前完成VOYAGE研究的患儿）中，任何治疗突发不良事件（TEAE）的患者数量和比例。本研究采用描述性统计分析。本研究已在ClinicalTrials.gov上注册（NCT03560466；EXCURSION）。
结果：在2018年6月21日至2020年8月18日期间，完成VOYAGE研究的患儿有资格参加EXCURSION研究。在EXCURSION研究期间，安全性概况及报告TEAE的患儿比例与母研究（VOYAGE）期间观察到的情况一致。在总体人群中，365名患儿中有232名（63.6%）至少出现过1次TEAE（度普利尤单抗/度普利尤单抗组：147[61.3%]；安慰剂/度普利尤单抗组：85[68%]）。最常报告的TEAE是鼻咽炎、咽炎和上呼吸道感染。
结论：在EXCURSION研究中，度普利尤单抗长期治疗具有良好的耐受性和可接受的安全性。
Assessment of long-term safety and efficacy of dupilumab in children with asthma (LIBERTY ASTHMA EXCURSION): an open-label extension study.
Bacharier LB, Maspero JF, Katelaris CH, Fiocchi AG, Gagnon R, de Mir I, Guilbert TW, Jackson DJ, Staudinger HW, Laws E, Mannent LP, Akinlade B, Maloney J, Tawo K, Khokhar FA, Li N, Hardin M, Abdulai RM, Lederer DJ, Robinson LB; Liberty Asthma EXCURSION Investigators.
Abstract
BACKGROUND:Dupilumab efficacy and safety in children aged 6-11 years with uncontrolled, moderate-to-severe asthma were shown in the VOYAGE study-a 52-week, multinational, multicentre, phase 3 randomised, double-blind, placebo-controlled trial.
OBJECTIVE:We aimed to evaluate the long-term safety and efficacy of dupilumab in children with moderate-to-severe asthma who previously participated in the VOYAGE study.
METHODS:365 of 408 children with moderate-to-severe asthma from VOYAGE enrolled in EXCURSION, a 52 week, open-label extension study conducted at 70 centres across 17 countries. 240 children continued with add-on dupilumab (dosed according to bodyweight: 100 mg for those weighing ≤30 kg and 200 mg for those weighing more than 30 kg at EXCURSION baseline) once every 2 weeks administered by subcutaneous injection (dupilumab/dupilumab group) and 125 children on placebo during VOYAGE initiated dupilumab (100 or 200 mg, according to bodyweight), once every 2 weeks administered by subcutaneous injection (placebo/dupilumab group). Following a protocol amendment, for a subset of children weighing 30 kg or less, the dose was changed to 300 mg once every 4 weeks. The primary endpoint for the open-label extension study was the number and proportion of patients with any treatment-emergent adverse event (TEAE) during the 52-week study period in the overall population (defined as children aged 6-11 years old with moderate-to-severe asthma who previously completed VOYAGE). Statistical analyses were descriptive. This study is registered with ClinicalTrials.gov (NCT03560466; EXCURSION).
RESULTS:Children who completed VOYAGE were eligible to enrol in EXCURSION between June 21, 2018 and Aug 18, 2020. During EXCURSION, the safety profile and proportion of patients reporting TEAEs were consistent with those observed during the parent study (VOYAGE). In the overall population, 232 (63·6%) of 365 patients experienced at least one TEAE (dupilumab/dupilumab: 147 [61·3%]; placebo/dupilumab: 85 [68·0%]). The most frequently reported TEAEs were nasopharyngitis, pharyngitis, and upper respiratory tract infections.
CONCLUSION: In EXCURSION, long-term treatment with dupilumab was well tolerated with an acceptable safety profile.
背景：VOYGE研究为期52周，是一项多国、多中心、3期随机、双盲、安慰剂对照试验。该研究证实了度普利尤单抗对6-11岁罹患未控制中重度哮喘儿童的有效性和安全性。
目的：本研究旨在评估度普利尤单抗对曾参与VOYAGE研究的中重度哮喘患儿的长期安全性和有效性。
方法：EXCURSION研究是一项为期52周的开放标签扩展研究，共纳入365名VOYAGE研究中的中重度哮喘患儿（共408名），在17个国家、70个中心开展。其中，度普利尤单抗/度普利尤单抗组的240名患儿继续每2周皮下注射一次度普利尤单抗（根据体重给药：在EXCURSION基线时体重≤30 kg的患儿为100 mg，体重＞30 kg的患儿为200 mg）；安慰剂/度普利尤单抗组的125名患儿在VOYAGE研究期间应用安慰剂，在本研究中启动度普利尤单抗（根据体重用量100或200 mg），每2周皮下注射一次。研究方案修订后，对于体重≤30公斤的患儿亚组，用量调整为每4周一次，每次300毫克。开放标签扩展研究的主要终点为在52周的研究期间，在总人群（定义为6-11岁患有中重度哮喘且先前完成VOYAGE研究的患儿）中，任何治疗突发不良事件（TEAE）的患者数量和比例。本研究采用描述性统计分析。本研究已在ClinicalTrials.gov上注册（NCT03560466；EXCURSION）。
结果：在2018年6月21日至2020年8月18日期间，完成VOYAGE研究的患儿有资格参加EXCURSION研究。在EXCURSION研究期间，安全性概况及报告TEAE的患儿比例与母研究（VOYAGE）期间观察到的情况一致。在总体人群中，365名患儿中有232名（63.6%）至少出现过1次TEAE（度普利尤单抗/度普利尤单抗组：147[61.3%]；安慰剂/度普利尤单抗组：85[68%]）。最常报告的TEAE是鼻咽炎、咽炎和上呼吸道感染。
结论：在EXCURSION研究中，度普利尤单抗长期治疗具有良好的耐受性和可接受的安全性。
(中日友好医院呼吸与危重症医学科 张婧媛 摘译 林江涛 审校)
(Lancet Respir Med. 2024 Jan;12(1):45-54. doi: 10.1016/S2213-2600(23)00303-X.)
(Lancet Respir Med. 2024 Jan;12(1):45-54. doi: 10.1016/S2213-2600(23)00303-X.)
Assessment of long-term safety and efficacy of dupilumab in children with asthma (LIBERTY ASTHMA EXCURSION): an open-label extension study.
Bacharier LB, Maspero JF, Katelaris CH, Fiocchi AG, Gagnon R, de Mir I, Guilbert TW, Jackson DJ, Staudinger HW, Laws E, Mannent LP, Akinlade B, Maloney J, Tawo K, Khokhar FA, Li N, Hardin M, Abdulai RM, Lederer DJ, Robinson LB; Liberty Asthma EXCURSION Investigators.
Abstract
BACKGROUND:Dupilumab efficacy and safety in children aged 6-11 years with uncontrolled, moderate-to-severe asthma were shown in the VOYAGE study-a 52-week, multinational, multicentre, phase 3 randomised, double-blind, placebo-controlled trial.
OBJECTIVE:We aimed to evaluate the long-term safety and efficacy of dupilumab in children with moderate-to-severe asthma who previously participated in the VOYAGE study.
METHODS:365 of 408 children with moderate-to-severe asthma from VOYAGE enrolled in EXCURSION, a 52 week, open-label extension study conducted at 70 centres across 17 countries. 240 children continued with add-on dupilumab (dosed according to bodyweight: 100 mg for those weighing ≤30 kg and 200 mg for those weighing more than 30 kg at EXCURSION baseline) once every 2 weeks administered by subcutaneous injection (dupilumab/dupilumab group) and 125 children on placebo during VOYAGE initiated dupilumab (100 or 200 mg, according to bodyweight), once every 2 weeks administered by subcutaneous injection (placebo/dupilumab group). Following a protocol amendment, for a subset of children weighing 30 kg or less, the dose was changed to 300 mg once every 4 weeks. The primary endpoint for the open-label extension study was the number and proportion of patients with any treatment-emergent adverse event (TEAE) during the 52-week study period in the overall population (defined as children aged 6-11 years old with moderate-to-severe asthma who previously completed VOYAGE). Statistical analyses were descriptive. This study is registered with ClinicalTrials.gov (NCT03560466; EXCURSION).
RESULTS:Children who completed VOYAGE were eligible to enrol in EXCURSION between June 21, 2018 and Aug 18, 2020. During EXCURSION, the safety profile and proportion of patients reporting TEAEs were consistent with those observed during the parent study (VOYAGE). In the overall population, 232 (63·6%) of 365 patients experienced at least one TEAE (dupilumab/dupilumab: 147 [61·3%]; placebo/dupilumab: 85 [68·0%]). The most frequently reported TEAEs were nasopharyngitis, pharyngitis, and upper respiratory tract infections.
CONCLUSION: In EXCURSION, long-term treatment with dupilumab was well tolerated with an acceptable safety profile.
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