Department of Pulmonology, University of Groningen, University Medical Center Groningen, and Groningen Research Institute for Asthma and COPD, Groningen, Netherlands.
Allergy and Respiratory Research Unit, Fundación Centro Investigacion de Enfermedades Alergicas y Respiratorias, Buenos Aires, Argentina.
Lancet Respir Med. 2020 Oct;8(10):1000-1012. doi: 10.1016/S2213-2600(20)30190-9. Epub 2020 Jul 9.
Patients with asthma who are inadequately controlled on inhaled corticosteroid-long-acting β-adrenoceptor agonist (ICS-LABA) combinations might benefit from the addition of a long-acting muscarinic receptor antagonist. The aim of the IRIDIUM study was to assess the efficacy and safety of a once-daily, single-inhaler combination of mometasone furoate, indacaterol acetate, and glycopyrronium bromide (MF-IND-GLY) versus ICS-LABA in patients with inadequately controlled asthma.
In this 52-week, double-blind, double-dummy, parallel-group, active-controlled phase 3 study, patients were recruited from 415 sites across 41 countries. Patients aged 18 to 75 years with symptomatic asthma despite treatment with medium-dose or high-dose ICS-LABA, at least one exacerbation in the previous year, and a percentage of predicted FEV of less than 80% were included. Enrolled patients were randomly assigned (1:1:1:1:1) via interactive response technology to receive medium-dose or high-dose MF-IND-GLY (80 μg, 150 μg, 50 μg; 160 μg, 150 μg, 50 μg) or MF-IND (160 μg, 150 μg; 320 μg, 150 μg) once daily via Breezhaler, or high-dose fluticasone-salmeterol (FLU-SAL; 500 μg, 50 μg) twice daily via Diskus. The primary outcome was change from baseline in trough FEV with MF-IND-GLY versus MF-IND at week 26 in patients in the full analysis set, analysed by means of a mixed model for repeated measures. Safety was assessed in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT02571777, and is completed.
Between Dec 8, 2015, and Jun 14, 2019, 3092 of 4851 patients screened were randomly assigned (medium-dose MF-IND-GLY, n=620; high-dose MF-IND-GLY, n=619; medium-dose MF-IND, n=617; high-dose MF-IND, n=618; high-dose FLU-SAL, n=618). 2747 (88·8%) patients completed the 52-week treatment and 321 (10·4%) started but discontinued study treatment prematurely. Medium-dose MF-IND-GLY (treatment difference [Δ] 76 mL [95% CI 41-111]; p<0·001) and high-dose MF-IND-GLY (Δ 65 mL [31-99]; p<0·001) showed superior improvement in trough FEV versus corresponding doses of MF-IND at week 26. Improvements in trough FEV were greater for both medium-dose MF-IND-GLY (99 mL [64-133]; p<0·001) and high-dose MF-IND-GLY (119 mL [85-154]; p<0·001) than for high-dose FLU-SAL at week 26. Overall, the incidence of adverse events was balanced across the treatment groups. Seven deaths were reported (one with medium-dose MF-IND-GLY, two with high-dose MF-IND-GLY, and four with high-dose MF-IND) during the study; none of these deaths was considered by the investigators to be caused by study drugs or other study-related factors.
Once-daily, single-inhaler MF-IND-GLY improved lung function versus ICS-LABA combinations (MF-IND and FLU-SAL) in patients with inadequately controlled asthma. The safety profile was similar across treatment groups. MF-IND-GLY therefore constitutes a good treatment option in these patients.
Novartis Pharmaceuticals.
对于吸入皮质激素-长效β-激动剂（ICS-LABA）联合治疗控制不佳的哮喘患者，添加长效毒蕈碱受体拮抗剂可能会获益。IRIDIUM 研究旨在评估每日一次、单吸入器糠酸莫米松/乌美溴铵/格隆溴铵（MF-IND-GLY）与 ICS-LABA 联合治疗控制不佳哮喘患者的疗效和安全性。
这是一项为期 52 周、双盲、双模拟、平行分组、阳性对照的 3 期研究，在 41 个国家的 415 个地点招募了患者。年龄在 18 至 75 岁之间，接受中剂量或高剂量 ICS-LABA 治疗仍有症状，过去 1 年至少有 1 次加重，且预计 FEV 百分比<80%的患者入选。入组患者通过交互式反应技术以 1:1:1:1:1 的比例随机分配（1:1:1:1:1）接受中剂量或高剂量 MF-IND-GLY（80μg、150μg、50μg；160μg、150μg、50μg）或 MF-IND（160μg、150μg；320μg、150μg）每日一次，通过 Breezhaler 给药，或高剂量氟替卡松-沙美特罗（FLU-SAL；500μg、50μg）每日 2 次，通过 Diskus 给药。主要终点是在治疗 26 周时，全分析集患者中 MF-IND-GLY 与 MF-IND 相比，谷值 FEV 的变化，通过重复测量混合模型进行分析。所有至少接受过一剂研究药物的患者均进行了安全性评估。这项研究在 ClinicalTrials.gov 上注册，NCT02571777，并已完成。
2015 年 12 月 8 日至 2019 年 6 月 14 日，在 4851 名筛查患者中，有 3092 名患者被随机分配（中剂量 MF-IND-GLY，n=620；高剂量 MF-IND-GLY，n=619；中剂量 MF-IND，n=617；高剂量 MF-IND，n=618；高剂量 FLU-SAL，n=618）。2747 名（88.8%）患者完成了 52 周的治疗，321 名（10.4%）患者提前开始但停止了研究治疗。与相应剂量的 MF-IND 相比，中剂量 MF-IND-GLY（治疗差异[Δ]76mL[95%CI 41-111]；p<0·001）和高剂量 MF-IND-GLY（Δ65mL[31-99]；p<0·001）在谷值 FEV 方面表现出更好的改善。与高剂量 FLU-SAL 相比，中剂量 MF-IND-GLY（99mL[64-133]；p<0·001）和高剂量 MF-IND-GLY（119mL[85-154]；p<0·001）在谷值 FEV 方面的改善更为显著。总体而言，治疗组之间的不良反应发生率平衡。研究期间报告了 7 例死亡（1 例使用中剂量 MF-IND-GLY，2 例使用高剂量 MF-IND-GLY，4 例使用高剂量 MF-IND）；研究者认为这些死亡均与研究药物或其他与研究相关的因素无关。
每日一次、单吸入器糠酸莫米松/乌美溴铵/格隆溴铵改善了控制不佳的哮喘患者的肺功能，与 ICS-LABA 联合治疗（MF-IND 和 FLU-SAL）相比。治疗组之间的安全性特征相似。因此，MF-IND-GLY 是这些患者的一个很好的治疗选择。
诺华制药公司。
