Unit of Respiratory Medicine, Dept of Experimental Medicine, University of Rome "Tor Vergata", Rome, Italy
Unit of Respiratory Medicine, Dept of Experimental Medicine, University of Rome "Tor Vergata", Rome, Italy.
Eur Respir J. 2021 Sep 2;58(3). doi: 10.1183/13993003.04233-2020. Print 2021 Sep.
Conflicting evidence is currently available concerning the impact on asthma exacerbation of triple inhaled corticosteroid (ICS)/long-acting β-adrenoceptor agonist (LABA)/long-acting muscarinic receptor antagonist (LAMA) fixed-dose combination (FDC).Since meta-analyses allow settling controversies of apparently inconsistent results, we performed a network meta-analysis of phase III randomised controlled trials including 9535 patients to assess the effect of ICS/LABA/LAMA combinations in uncontrolled asthma.Triple combination therapies with an ICS administered at high dose (HD) were more effective (p<0.05) than medium-dose (MD) ICS/LABA/LAMA FDC and both MD and HD ICS/LABA FDCs against moderate to severe exacerbation (relative risk 0.61-0.80) and increasing trough forced expiratory volume in 1 s (from +33 to +114 mL). Triple combination therapies including HD ICS were superior (p<0.05) to MD ICS/LABA/LAMA FDC in preventing severe exacerbation (relative risk 0.46-0.65), but not with respect to moderate exacerbation (p>0.05). Triple combination therapies were equally effective on asthma control, with no safety concerns.This quantitative synthesis suggests that ICS/LABA/LAMA FDCs are effective and safe in uncontrolled asthma, and that the dose of ICS in the combination represents the discriminating factor to treat patients with a history of moderate or severe exacerbation.
目前关于三重复吸入皮质激素（ICS）/长效β-肾上腺素能受体激动剂（LABA）/长效毒蕈碱受体拮抗剂（LAMA）固定剂量组合（FDC）对哮喘加重影响的证据相互矛盾。由于荟萃分析可以解决明显不一致结果的争议，我们对包括 9535 例患者的 III 期随机对照试验进行了网络荟萃分析，以评估 ICS/LABA/LAMA 联合治疗在未控制哮喘中的疗效。高剂量（HD）ICS 三联治疗比中剂量（MD）ICS/LABA/LAMA FDC 更有效（p<0.05），也比 MD 和 HD ICS/LABA FDC 更有效（p<0.05）预防中度至重度加重（相对风险 0.61-0.80）和增加谷值用力呼气量（从+33 到+114mL）。包括 HD ICS 的三联治疗在预防重度加重方面优于 MD ICS/LABA/LAMA FDC（相对风险 0.46-0.65）（p<0.05），但在预防中度加重方面无差异（p>0.05）。三联治疗在哮喘控制方面同样有效，无安全性问题。这项定量综合研究表明，ICS/LABA/LAMA FDC 在未控制的哮喘中是有效和安全的，并且联合用药中 ICS 的剂量是治疗有中度或重度加重史患者的区分因素。
