噻托溴铵联合治疗在严重症状性哮喘患儿中的一项III期随机对照试验
2017/12/20
摘要
背景：对成年和青少年中重度症状性哮喘患者的研究表明，噻托溴铵作为吸入皮质类固醇激素（ICSs）的辅助治疗有效，无论是否使用其他维持治疗。
目的：在这项对有严重症状的哮喘儿童使用噻托溴铵治疗的III期试验的第一阶段，我们尝试评估每日吸入一次噻托溴铵作为辅助治疗，对于联合应用高剂量ICS与1个或更多的控制性药物，或联合应用中剂量ICS与2个或更多的控制性药物的患者的有效性和安全性。
方法：在这项12周、双盲、安慰剂对照、平行组试验中，401名6岁至11岁的患者随机接受每日一次的噻托溴铵5μG（2喷2.5μG）或2.5μG（2喷1.25μG），或安慰剂（2喷），作为既往治疗基础上的一项附加治疗。
结果：与安慰剂组相比，噻托溴铵5μG，而不是2.5μg，作为附加治疗能改善试验的主要终点——用药后3小时内FEV1峰值(5 μg, 139 mL [95% CI, 75-203; P < .001]; 2.5 μg, 35 mL [95% CI, -28 to 99; P = .27])，和核心次要终点——FEV1谷值(5 μg, 87 mL [95% CI, 19-154; P = .01]; 2.5 μg, 18 mL [95% CI, -48 to 85; P = .59])。噻托溴铵的安全性和耐受性与安慰剂相当。
结论：每日一次吸入噻托溴铵5μG能够改善肺功能，同时其作为严重的症状性哮喘儿童在ICS联合其他维持治疗药物基础上的附加治疗，能够被良好耐受。
A phase III randomized controlled trial of tiotropium add-on therapy in children with severe symptomatic asthma.
Szefler SJ, Murphy K, Harper T 3rd, Boner A, Laki I, Engel M, El Azzi G, Moroni-Zentgraf P, Finnigan H, Hamelmann E
Abstract
BACKGROUND:Studies in adults and adolescents have demonstrated that tiotropium is efficacious as an add-on therapy to inhaled corticosteroids (ICSs) with or without other maintenance therapies in patients with moderate or severe symptomatic asthma.
OBJECTIVE:We sought to assess the efficacy and safety of once-daily tiotropium Respimat add-on therapy to high-dose ICS with 1 or more controller medications, or medium-dose ICS with 2 or more controller medications, in the first phase III trial of tiotropium in children with severe symptomatic asthma.
METHODS:In this 12-week, double-blind, placebo-controlled, parallel-group trial, 401 participants aged 6 to 11 years were randomized to receive once-daily tiotropium 5 μg (2 puffs of 2.5 μg) or 2.5 μg (2 puffs of 1.25 μg), or placebo (2 puffs), administered through the Respimat device as add-on to background therapy.
RESULTS:Compared with placebo, tiotropium 5 μg, but not 2.5 μg, add-on therapy improved the primary end point, peak FEV1 within 3 hours after dosing (5 μg, 139 mL [95% CI, 75-203; P < .001]; 2.5 μg, 35 mL [95% CI, -28 to 99; P = .27]), and the key secondary end point, trough FEV1 (5 μg, 87 mL [95% CI, 19-154; P = .01]; 2.5 μg, 18 mL [95% CI, -48 to 85; P = .59]). The safety and tolerability of tiotropium were comparable with those of placebo.
CONCLUSIONS:Once-daily tiotropium Respimat 5 μg improved lung function and was well tolerated as add-on therapy to ICS with other maintenance therapies in children with severe symptomatic asthma.
背景：对成年和青少年中重度症状性哮喘患者的研究表明，噻托溴铵作为吸入皮质类固醇激素（ICSs）的辅助治疗有效，无论是否使用其他维持治疗。
目的：在这项对有严重症状的哮喘儿童使用噻托溴铵治疗的III期试验的第一阶段，我们尝试评估每日吸入一次噻托溴铵作为辅助治疗，对于联合应用高剂量ICS与1个或更多的控制性药物，或联合应用中剂量ICS与2个或更多的控制性药物的患者的有效性和安全性。
方法：在这项12周、双盲、安慰剂对照、平行组试验中，401名6岁至11岁的患者随机接受每日一次的噻托溴铵5μG（2喷2.5μG）或2.5μG（2喷1.25μG），或安慰剂（2喷），作为既往治疗基础上的一项附加治疗。
结果：与安慰剂组相比，噻托溴铵5μG，而不是2.5μg，作为附加治疗能改善试验的主要终点——用药后3小时内FEV1峰值(5 μg, 139 mL [95% CI, 75-203; P < .001]; 2.5 μg, 35 mL [95% CI, -28 to 99; P = .27])，和核心次要终点——FEV1谷值(5 μg, 87 mL [95% CI, 19-154; P = .01]; 2.5 μg, 18 mL [95% CI, -48 to 85; P = .59])。噻托溴铵的安全性和耐受性与安慰剂相当。
结论：每日一次吸入噻托溴铵5μG能够改善肺功能，同时其作为严重的症状性哮喘儿童在ICS联合其他维持治疗药物基础上的附加治疗，能够被良好耐受。
(中日友好医院呼吸与危重症医学科 张科文 摘译 林江涛 审校)
(J Allergy Clin Immunol.2017 Nov;140(5):1277-1287)
(J Allergy Clin Immunol.2017 Nov;140(5):1277-1287)
A phase III randomized controlled trial of tiotropium add-on therapy in children with severe symptomatic asthma.
Szefler SJ, Murphy K, Harper T 3rd, Boner A, Laki I, Engel M, El Azzi G, Moroni-Zentgraf P, Finnigan H, Hamelmann E
Abstract
BACKGROUND:Studies in adults and adolescents have demonstrated that tiotropium is efficacious as an add-on therapy to inhaled corticosteroids (ICSs) with or without other maintenance therapies in patients with moderate or severe symptomatic asthma.
OBJECTIVE:We sought to assess the efficacy and safety of once-daily tiotropium Respimat add-on therapy to high-dose ICS with 1 or more controller medications, or medium-dose ICS with 2 or more controller medications, in the first phase III trial of tiotropium in children with severe symptomatic asthma.
METHODS:In this 12-week, double-blind, placebo-controlled, parallel-group trial, 401 participants aged 6 to 11 years were randomized to receive once-daily tiotropium 5 μg (2 puffs of 2.5 μg) or 2.5 μg (2 puffs of 1.25 μg), or placebo (2 puffs), administered through the Respimat device as add-on to background therapy.
RESULTS:Compared with placebo, tiotropium 5 μg, but not 2.5 μg, add-on therapy improved the primary end point, peak FEV1 within 3 hours after dosing (5 μg, 139 mL [95% CI, 75-203; P < .001]; 2.5 μg, 35 mL [95% CI, -28 to 99; P = .27]), and the key secondary end point, trough FEV1 (5 μg, 87 mL [95% CI, 19-154; P = .01]; 2.5 μg, 18 mL [95% CI, -48 to 85; P = .59]). The safety and tolerability of tiotropium were comparable with those of placebo.
CONCLUSIONS:Once-daily tiotropium Respimat 5 μg improved lung function and was well tolerated as add-on therapy to ICS with other maintenance therapies in children with severe symptomatic asthma.
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贝那利珠单抗治疗高剂量吸入皮质类固醇激素和长效β2受体激动剂（SIROCCO）的重度哮喘患者的疗效和安全性：一项随机，多
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噻托溴铵呼吸道附加物在症状性哮喘中有效，不依赖于T2表型
