TY - JOUR T1 - Triple therapy in uncontrolled asthma: a network meta-analysis of phase III studies JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.04233-2020 VL - 58 IS - 3 SP - 2004233 AU - Paola Rogliani AU - Beatrice Ludovica Ritondo AU - Luigino Calzetta Y1 - 2021/09/01 UR - http://erj.ersjournals.com/content/58/3/2004233.abstract N2 - Conflicting evidence is currently available concerning the impact on asthma exacerbation of triple inhaled corticosteroid (ICS)/long-acting β2-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.Triple combination therapy by adding either a LAMA to ICS/LABA FDC or escalating ICS on a background of ICS/LABA/LAMA FDC may reduce severe exacerbations and improve lung function; adding a LAMA along with escalating ICS provides incremental effects https://bit.ly/39NuNKb ER -