Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) Triple Therapy Compared with Other Therapies for the Treatment of COPD: A Network Meta-Analysis

Abstract

Introduction: Randomized controlled trials (RCTs) comparing triple therapies (inhaled corticosteroid [ICS], long-acting b 2 -agonist [LABA], and long-acting muscarinic antagonist [LAMA]) for the treatment of chronic obstructive pulmonary disease (COPD) are limited. This network meta-analysis (NMA) investigated the comparative efficacy of single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/ UMEC/VI) versus any triple (ICS/LABA/LAMA) combinations and dual therapies in patients with COPD. Methods: This NMA was conducted on the basis of a systematic literature review (SLR), which identified RCTs in adults aged at least 40 years with COPD. The RCTs compared different ICS/LABA/LAMA combinations or an

Letter to the Editor Regarding “Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) Triple Therapy Compared with Other Therapies for the Treatment of COPD: A Network Meta-Analysis”

“…However, the random-effects model, as recommended per best practice, showed no significant treatment-effect differences, due to wide CIs driven by between-study heterogeneity. Given the methodological issues, selective reporting of fixed-effects model results, and failure to disclose the random-effects model results, which we believe to be not significant per our replicate analysis, we do not agree with Ismaila et al that FF/UMEC/VI showed statistically significant improvements in annualized moderate/severe exacerbation rates versus budesonide/glycopyrronium bromide/formoterol fumarate (BUD/GLY/FOR) [1]. Notably, their finding contradicts four other peer-reviewed NMA publications, including two from independent researchers [8,9], all of which used random-effects models to account for heterogeneity and reported no significant exacerbation rate differences between triple therapies in patients with chronic obstructive pulmonary disease [8][9][10][11].…”

“…We read with interest the publication by Ismaila et al in Advances in Therapy entitled ''Fluticasone Furoate/Umeclidinium/Vilanterol (FF/ UMEC/VI) Triple Therapy Compared with Other Therapies for the Treatment of COPD: A Network Meta-Analysis'' [1]. Network metaanalysis (NMA) is an important statistical technique, often used to make indirect treatment comparisons when no direct head-to-head studies are available [2].…”

“…Per best practice, when NMAs are undertaken in the presence of heterogeneity, random-effects models are recommended to account for heterogeneity [3][4][5][6]. Ismaila et al noted a large amount of between-study heterogeneity for their severe exacerbation analysis; these results were therefore not deemed robust and not reported [1]. I 2 is a standard statistical measure of homogeneity/heterogeneity [4,7], and Ismaila et al report an I 2 of 86.59% for the network of studies reporting combined moderate/severe exacerbation rates [1]; this is classed as considerable heterogeneity, per Cochrane (I 2 of 75-100%, highest category) [4], but the authors did not question the robustness of these findings [1].…”

“…I 2 is a standard statistical measure of homogeneity/heterogeneity [4,7], and Ismaila et al report an I 2 of 86.59% for the network of studies reporting combined moderate/severe exacerbation rates [1]; this is classed as considerable heterogeneity, per Cochrane (I 2 of 75-100%, highest category) [4], but the authors did not question the robustness of these findings [1]. Ismaila et al subsequently analyzed a smaller group of studies with C 24 weeks' follow-up ''to account for heterogeneity induced by differences in length of follow-up'', but I 2 increased to 94.93% [1], suggesting that heterogeneity was not substantially caused by differences in follow-up length but by other factors. However, the authors did not further explore possible reasons for this heterogeneity, nor, as detailed below, did they report the results from a random-effects model, which would account for the heterogeneity.…”

Triple Therapy for COPD: Historical Perspective and Current Controversies

“…More recently, another network metanalysis was released, on this occasion funded and led by GlaxoSmithKline 72 . The authors reported a favorable efficacy effect with fluticasone furoate triple therapy at 24 weeks in terms of lung function, annualized rate of moderatesevere exacerbations, health status and rescue medication use.…”