NMA class comparison data in COPD

FF/UMEC/VI versus triple and dual bronchodilator therapies

Key outcomes of interest¹

figure-showing-key-outcomes-of-interest-Single-inhaler-FF/UMEC/VI (100/62.5/25-micrograms)-administered-once-daily-was-compared-to-other-triple-and-dual-therapies,-including-multiple-inhaler-triple-therapies-and-the-following-single-inhaler-triple-therapies:-BUD/GLY/FOR-(320/18/9.6-micrograms),-administered-twice-daily,-and-BDP/FOR/GLY-(100/6/12.5-micrograms)-administered-twice-daily.-TIO-monotherapy-was-also-included-as-a-comparator.-The-outcomes-of-interest-include-difference-in-incidence-rates-of-annualised-moderate/severe-exacerbations-at-24-weeks,-mean-difference-in-change-from-baseline-in-trough-FEV1-at-weeks-12-and-24,-mean-difference-in-change-from-baseline-in-SGRQ-total-score-at-weeks-12-and-24-and-SGRQ-responder-analysis-at-week-12

*TIO monotherapy also included as a comparator

Methodology and networks of evidence¹

SLR identified RCTs in adults aged ≥40 years with COPD, comparing different ICS/LABA/LAMA combinations with each other, and ICS/LABA/LAMA combinations with any dual treatment regimen (ICS/LABA or LAMA/LABA)

SLR of published studies performed up to October 2020 included 10,030 initially identified abstracts

NMA informed by 23 clinical studies:

17 reported moderate/severe exacerbation endpoints

15 reporting trough FEV₁ at 12 weeks and 5 reported trough FEV₁ at 24 weeks

10 trials reporting SGRQ total score at 12 weeks and 5 at 24 weeks, with one trial in both networks

Click here to learn about methodological considerations
Analysis is limited by differences in study design and patient characteristics, definition of events, and inclusion/exclusion criteria of each study.

All analyses were conducted using a frequentist weighted regression based approach.¹

Both fixed effects (FE) and random effects (RE) models were used and in the absence of heterogeneity results of RE models were similar to the FE model results. RE models automatically accounted for heterogeneity when present.¹

The results of heterogeneity and consistency checks showed consistencies of trough FEV₁ reporting at 12 and 24 weeks.¹

Substantial heterogeneity was observed across trials when defining severe exacerbations, therefore moderate and severe exacerbations were pooled to reduce the impact of heterogeneity.¹

For trough FEV₁ and SGRQ total score no comparisons for FF/UMEC/VI versus comparators was feasible at 52 weeks due to the lack of a data. SGRQ responder analysis was only carried out at 12 week due to lack of data.

^{FE, fixed effect; FEV₁, forced expiratory volume in 1 second; RE, random effect; SGRQ, St George’s Respiratory Questionnaire.}

Click here to find out more about the SLR

PRISMA flow diagram of study selection process¹

Figure adapted with permission from Ismaila AS, et al. Adv Ther. 2022;39:3957-3978.
CSR, clinical study report; network meta-analysis; SLR systematic literature review.

Key SITT trials word cloud by population size^2-12

word-cloud-showing-the-key-single-inhaler-triple-therapy-trials-by-population-size-included-in-the-meta-analysis

Click here for more information on key trials included in the NMA

Study	Population size, duration and treatments	Key inclusion criteria	Primary endpoint(s)
ETHOS¹⁰	N=8509 52 weeks BUD/GLY/FOR BD (320/18/9.6 µg) BUD/GLY/FOR BD (160/18/9.6 µg) BUD/FOR BD (320/9.6 µg) GLY/FOR BD (18/9.6 µg)	40–80 years of age CAT score ≥10 FEV₁ 25–<50% predicted and ≥1 moderate/severe exacerbation in prior year^a OR FEV₁ ≥50% to ≤65% predicted, ≥2 moderate or ≥1 severe exacerbation in prior year	Annual rate of moderate or severe COPD exacerbations^a
FULFIL³	ITT N=1810, 24 weeks EXT N=430, 52 weeks FF/UMEC/VI QD (100/62.5/25 µg) BUD/FOR BD (400/12 µg)	≥40 years of age FEV₁ <50% predicted and CAT score ≥10 OR FEV₁ ≤50% to <80% predicted, CAT score ≥10 and ≥2 moderate or ≥1 severe exacerbation in prior year^b	Change from baseline in trough FEV₁ and SGRQ total score at Week 24
IMPACT⁴	N=10,355, 52 weeks FF/UMEC/VI QD (100/62.5/25 µg) FF/VI QD (100/25 µg) UMEC/VI QD (62.5/25 µg)	≥40 years of age CAT score ≥10 FEV₁ <50% predicted and ≥1 moderate or severe exacerbation in prior year OR FEV₁ 50–80% predicted and ≥2 moderate or 1 severe exacerbation in prior year^b	Annual rate of on-treatment moderate/severe exacerbations^b
KRONOS²	N=1896, 24 weeks BUD/GLY/FOR BD (320/18/9.6 µg) GLY/FOR BD (18/9.6 µg) BUD/FOR BD (320/9.6 µg) BUD/FOR BD (400/12 µg)	40–80 years of age CAT score ≥10 Post-bronchodilator % predicted FEV₁: ≥25% and <80% Not required to have had an exacerbation in prior year	FEV₁ AUC_0–4h over 24 weeks and change from baseline in morning pre-dose trough FEV₁ over 24 weeks
TRIBUTE¹¹	N=1532, 52 weeks BDP/FF/GLY (87/5/9 µg) two inhalations BD IND/GLY (85/43 µg), one inhalation QD	≥40 years of age FEV₁<50% ≥1 moderate or severe COPD exacerbation in the prior year^b CAT score ≥10 Use of ICS/LABA, ICS/LAMA, LABA/LAMA or LAMA (not triple therapy) for ≥2 months before screening	Rate of moderate-to-severe exacerbations^b
TRILOGY⁷	N=1368 BDP/GLY/FOR (100/12.5/6 µg) BD BDP/FOR (100/6 µg) BD	≥40 years of age CAT score ≥10, BDI focal score ≤10 FEV₁ <50% ≥1 moderate/severe exacerbation in prior year^b	Change from baseline to Week 26: Pre-dose (morning) FEV₁ 2-hour post-dose FEV₁ TDI focal score
TRINITY⁸	N=2691 52 weeks BDP/GLY/FOR (100/12.5/6 µg) BD TIO (18 µg) QD BDP/FOR (100/6 µg) BD	≥40 years of age Current/former smoker Post-bronchodilator FEV₁ <50% ≥1 moderate or severe COPD exacerbation in the prior 12 months^b CAT score ≥10	Rate of moderate-to-severe COPD exacerbations^b over 52 weeks treatment (BDP/GLY/FOR vs TIO)
TRISTAR^9,13,14	N=1157 26 weeks BDP/FOR/GLY (100/6/12.5 µg) TIO (18 µg) FF/VI (100/25 µg)	CAT score ≥10 Severe or very severe airflow limitation ≥1 exacerbation in the prior year^b	Change from baseline in SGRQ total score at Week 26
200812⁵	N=1311 24 weeks FF/UMEC/VI QD (100/62.5/25 µg) FF/VI QD (100/25 µg) + UMEC QD (62.5 µg)	≥40 years of age CAT score ≥10 Post-bronchodilator FEV₁ <50% predicted and ≥1 moderate/ severe exacerbation in the prior 12 months^b OR Post-bronchodilator FEV₁≥50% to <80% predicted and ≥2 moderate or ≥1 severe exacerbation in the prior 12 months^b	Change from baseline in trough FEV₁ at Week 24
207608⁶	N=728 12 weeks FF/UMEC/VI (100/62.5/25 µg) QD BUD/FOR (200/6 µg) BD + TIO (18 µg) QD	≥40 years of age Post-bronchodilator FEV₁ <50% predicted OR <80% predicted and ≥2 moderate or 1 severe exacerbation in previous 12 months CAT score ≥10	Weighted mean CFB in FEV₁ over 0–24 hours at Week 12
207609⁶	N=732 12 weeks FF/UMEC/VI (100/62.5/25 µg) QD BUD/FOR (200/6 µg) BD + TIO (18 µg) QD	≥40 years of age Post-bronchodilator FEV₁ <50% predicted OR <80% predicted and ≥2 moderate or 1 severe exacerbation in previous 12 months CAT score ≥10	Weighted mean CFB in FEV₁over 0–24 hours at Week 12
207626¹²	N=800 12 weeks FF/UMEC/VI (100/62.5/25 µg) QD TIO (18 µg) QD	≥40 years of age Post-bronchodilator FEV₁ <50% predicted OR <80% predicted and ≥2 moderate or ≥1 severe exacerbation in previous 12 months^c CAT score ≥10	Change from baseline in trough FEV₁ at Day 85

^aModerate exacerbations were defined as those leading to treatment with systemic glucocorticoids, antibiotics, or both for at least 3 days; severe exacerbations were defined as those resulting in hospitalisation or death.^{10 b}Moderate exacerbations were defined as those that require treatment with systemic corticosteroids and/or antibiotics; severe exacerbations were defined as those requiring hospitalisation or resulting in death.^{3-5,7,8,11,14,15 c}Moderate exacerbations were defined as those that require treatment with systemic corticosteroids and/or antibiotics; severe exacerbations were defined as those requiring hospitalisation.¹²

AUC, area under the curve; BDP, beclomethasone dipropionate; BD, twice daily, BDI, Baseline Dyspnoea Index; BUD, budesonide; CAT, COPD Assessment Test; CFB, change from baseline; COPD, chronic obstructive pulmonary disease; EXT, extension; FF, fluticasone furoate; FEV₁, forced expiratory volume in 1 second; FOR, formoterol; GLY, glycopyrronium bromide; ICS, inhaled corticosteroid; IND, indacaterol; ITT, intent-to-treat; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic receptor antagonist; NMA, network meta-analysis; QD, once daily; SGRQ, St George’s Respiratory Questionnaire; SITT, single-inhaler triple therapy; TDI, Transition Dyspnoea Index; TIO, tiotropium; UMEC, umeclidinium bromide; VI, vilanterol.

Click here for more information on all the trials included in the NMA

Author, year	Study name/NCT number	Link
	UMEC 62.5 + FF/VI 100/25
Siler, 2015¹⁶	CSR-200109, NCT01957163	Link
Siler, 2015¹⁶	CSR-200110, NCT02119286	Link
	FF/UMEC/VI 100/62.5/25
Lipson, 2017³	FULFIL, NCT02345161	Link
Bremner, 2018⁵	CSR-200812, NCT02729051	Link
Lipson, 2018⁴	IMPACT, NCT02164513	Link
Ferguson, 2020⁶	CSR-207608, NCT03478683	Link
Ferguson, 2020⁶	CSR-207609, NCT03478696	Link
Bansal, 2021¹²	CSR-207626, NCT03474081	Link
	UMEC 62.5 + ICS/LABA
Sousa, 2016¹⁷	CSR-201314, NCT02257372	Link
Siler, 2016¹⁸	AC4116135 (GSK573719), NCT01772134	Link
Siler, 2016¹⁸	AC4116136 (GSK573719), NCT01772147	Link
	TIO 18 + BDP/FOR 100/6
Vestbo, 2017⁸	TRINITY, NCT01911364	Link
	TIO 18 + BUD/FOR 320/9
Lee, 2016^19,20	SECURE 1, NCT01397890	Link
Welte, 2009¹²	NCT00496470	Link
	BDP/GLY/FOR 100/12.5/6
Singh, 2016⁷	TRILOGY, NCT01917331	Link
NA – results posted on clinicaltrialregister.eu	TRISTAR, NCT02467452, 2014-001487-35	Link
Papi, 2018¹¹	TRIBUTE, NCT02579850	Link
	BUD/GLY/FOR 320/18/9.6
Ferguson, 2018²	KRONOS, NCT02497001	Link
Kerwin, 2019²²	KRONOS Extension (Safety population; US patients), NCT02536508	Link
Rabe, 2020¹⁰	ETHOS, NCT02465567	Link
	TIO 18 + FP/SAL 500/50
Frith, 2015²³	GLISTEN, NCT01513460	Link
Aaron, 2007²⁴	ISRCTN29870041	Link
	TIO 18 + FP/SAL 250/50
Hanania, 2012²⁵	ADC111114, NCT00784550	Link
Jung, 2012²⁶	NA	Link

KRONOS Extension (Safety population) NCT02536508 is listed for completeness but is not counted as a unique trial.
NA, not available.

Network of evidence informing analyses

Network of evidence informing annualised exacerbation analyses¹

network-meta-analysis-figure-showing-the-network-of-evidence-informing-the-annualised-exacerbation-analyses

Figure reproduced with permission from Ismaila AS, et al. Adv Ther. 2022. doi: 10.1007/s12325-022-02231-0.
Although monotherapies were not included in the comparison, TIO 18 remains in the results as this was an anchor in the network. Open-label trials: Jung 2012; SECURE 1; TRISTAR. Sousa 2016 and Siler 2016 studies could not be connected to the main network due to non-availability of a common comparator. *TRIBUTE dosage was BDP/FOR/GLY 100/6/10 µg. Inclusion criteria included patients aged ≥35 years in Aaron 2007, and patients aged 40–80 years in ETHOS, KRONOS and KRONOS EXT. Grey lines indicate instances where data were not available at the time point of interest and were not included in the analysis.

Network of evidence informing trough FEV₁ analysis at 12 weeks¹

network-meta-analysis-figure-showing-the-network-of-evidence-informing-the-trough-FEV1-analysis-at-12-weeks

Figure reproduced with permission from Ismaila AS, et al. Adv Ther. 2022;39:3957-3978. Although monotherapies were not included in the comparison, TIO 18 remains in the results as this was an anchor in the network. Open-label trials: Jung 2012; SECURE 1; TRISTAR. Sousa 2016 and Siler 2016 studies could not be connected to the main network due to non-availability of a common comparator. *TRIBUTE dosage was BDP/FOR/GLY 100/6/10 µg. Inclusion criteria included patients aged ≥35 years in Aaron 2007, and patients aged 40–80 years in ETHOS and KRONOS. Grey lines indicate instances where data were not available at the time point of interest and were not included in the analysis.

Network of evidence informing trough FEV₁ analysis at 24 weeks¹

network-meta-analysis-figure-showing-the-network-of-evidence-informing-the-trough-FEV1-analysis-at-24-weeks

Figure reproduced with permission from Ismaila AS, et al. Adv Ther. 2022;39:3957-3978. Although monotherapies were not included in the comparison, TIO 18 remains in the results as this was an anchor in the network. Open-label trials: Jung 2012; SECURE 1; TRISTAR. Sousa 2016 and Siler 2016 studies could not be connected to the main network due to non-availability of a common comparator. *TRIBUTE dosage was BDP/FOR/GLY 100/6/10 µg. Inclusion criteria included patients aged ≥35 years in Aaron 2007, and patients aged 40–80 years in ETHOS and KRONOS. Grey lines indicate instances where data were not available at the time point of interest and were not included in the analysis.

Network of evidence informing SGRQ total score analysis at 12 weeks¹

network-meta-analysis-figure-showing-the-network-of-evidence-informing-the-SGRQ-responders-at-12-weeks

Figure reproduced with permission from Ismaila AS, et al. Adv Ther. 2022;39:3957-3978. Although monotherapies were not included in the comparison, TIO 18 remains in the results as this was an anchor in the network. Open-label trials: Jung 2012; SECURE 1; TRISTAR. SECURE1 and Welte 2009 studies reported SGRQ-C scores; these data were not included in the analysis. Sousa 2016 and Siler 2016 studies could not be connected to the main network due to non-availability of a common comparator. *TRIBUTE dosage was BDP/FOR/GLY 100/6/10 µg. Inclusion criteria included patients aged ≥35 years in Aaron 2007, and patients aged 40–80 years in ETHOS, KRONOS and KRONOS EXT. Grey lines indicate instances where data were not available at the time point of interest and were not included in the analysis.

Network of evidence informing SGRQ total score analysis at 24 weeks¹

network-meta-analysis-figure-showing-the-network-of-evidence-informing-the-SGRQ-total-score-analysis-at-24-weeks

Figure reproduced with permission from Ismaila AS, et al. Adv Ther. 2022;39:3957-3978. Although monotherapies were not included in the comparison, TIO 18 remains in the results as this was an anchor in the network. Open-label trials: Jung 2012; SECURE 1; TRISTAR. SECURE1 and Welte 2009 studies reported SGRQ-C scores; these data were not included in the analysis. Sousa 2016 and Siler 2016 studies could not be connected to the main network due to non-availability of a common comparator. *TRIBUTE dosage was BDP/FOR/GLY 100/6/10 µg. Inclusion criteria included patients aged ≥35 years in Aaron 2007, and patients aged 40–80 years in ETHOS and KRONOS. Grey lines indicate instances where data were not available at the time point of interest and were not included in the analysis.

Network of evidence informing SGRQ responders at 12 weeks¹

network-meta-analysis-figure-showing-the-network-of-evidence-informing-the-SGRQ-total-score-analysis-at-12-weeks

Figure reproduced with permission from Ismaila AS, et al. Adv Ther. 2022;39:3957-3978. Although monotherapies were not included in the comparison, TIO 18 remains in the results as this was an anchor in the network. Open-label trials: Jung 2012; SECURE 1; TRISTAR. SECURE1 and Welte 2009 studies reported SGRQ-C scores; these data were not included in the analysis. Sousa 2016 and Siler 2016 studies could not be connected to the main network due to non-availability of a common comparator. *TRIBUTE dosage was BDP/FOR/GLY 100/6/10 µg. Inclusion criteria included patients aged ≥35 years in Aaron 2007, and patients aged 40–80 years in ETHOS and KRONOS. Grey lines indicate instances where data were not available at the time point of interest and were not included in the analysis.

Results: Exacerbations and lung function

Annualised exacerbations: FF/UMEC/VI versus comparators for all studies¹

forest-plot-showing-the-mean-difference-in-incidence-ratios-of-annualised-moderate/severe exacerbations-of-FF/UMEC/VI-(100/62.5/25)-versus-comparators-for-all-studies.-A-box-is-highlighting-three-values-for-FF/UMEC/VI-versus-BUD/GLY/FOR-(320/18/9.6),-BUD/GLY/FOR-(160/18/9.6)-and-BDP/FOR/GLY-(100/6/12.5)-with-the-incidence-rates-for-these-comparisons-being-0.62-(95-percent-confidence-interval-0.45-to-0.86),-0.61-(95-percent-confidence-interval-0.44-to-0.85)-and-0.73-(95-percent-confidence-interval-0.51-to-1.04)-respectively.-For-the-comparison-with-BUD/GLY/FOR-(320/18/9.6)-the-p-value-was-equal-to-0.0044.-For-the-comparison-with-BUD/GLY/FOR-(160/18/9.6)-the-p-value-was-equal-to-0.0034.-For-the-comparison-with-BDP/FOR/GLY-(100/6/12.5)-the-p-value-was-equal-to-0.0774

Figure adapted with permission from Ismaila AS, et al. Adv Ther. 2022;39:3957-3978. Frequentist NMA FE model, combined moderate/severe annual exacerbations. BUD/GLY/FOR 320/18/9.6 BD is the licenced dose for COPD.²⁷

Annualised exacerbations: FF/UMEC/VI versus comparators for studies with ≥24 weeks of follow-up¹

Figure adapted with permission from Ismaila AS, et al. Adv Ther. 2022;39:3957-3978. Frequentist NMA FE model, combined moderate/severe annual exacerbations. BUD/GLY/FOR 320/18/9.6 BD is the licenced dose for COPD.²⁷

Lung function: FF/UMEC/VI versus comparators at 12 weeks¹

forest-plot-showing-the-mean-difference-in-change-from-baseline-in-trough-FEV1-of-FF/UMEC/VI-(100/62.5/25)-versus-comparators-at-12-weeks.-A-box-is-highlighting-two-values-for-FF/UMEC/VI-versus-BUD/GLY/FOR-(320/18/9.6)-and-BDP/FOR/GLY-(100/6/12.5)-with-the-mean-differences-for-these-comparisons-being-99.40-(95-percent-confidence-interval-69.08-to-129.72)-and-46.70-(95-percent-confidence-interval-15.21-to-78.20)-respectively.-For-the-comparison-with-BUD/GLY/FOR-the-p-value-was-less-than-0.0001.-For-the-comparison-with-BDP/FOR/GLY-the-p-value-was-equal-to-0.0037

Figure adapted with permission from Ismaila AS, et al. Adv Ther. 2022;39:3957-3978. Frequentist NMA FE model. BUD/GLY/FOR 320/18/9.6 BD is the licenced dose for COPD.²⁷

Lung function: FF/UMEC/VI versus comparators at 24 weeks¹

Figure adapted with permission from Ismaila AS, et al. Adv Ther. 2022;39:3957-3978. Frequentist NMA FE model. BUD/GLY/FOR 320/18/9.6 BD is the licenced dose for COPD.²⁷

Results: Health status

SGRQ total score: FF/UMEC/VI versus comparators at 12 weeks¹

Forest-plot-showing-the-mean-difference-in-change-from-baseline-in-total-SGRQ-score-of-FF/UMEC/VI-(100/62.5/25)-versus-comparators-at-12-weeks.-A-box-is-highlighting-one-value-for-FF/UMEC/VI-versus-BDP/FOR/GLY-(100/6/12.5)-with-the-mean-differences-for-the-comparison-being-minus-1.43-(95-percent-confidence-interval-minus-3.47-to-0.61)-and-p-value-of-0.1687

Figure adapted with permission from Ismaila AS, et al. Adv Ther. 2022;39:3957-3978. Frequentist NMA FE model.

SGRQ total score: FF/UMEC/VI versus comparators at 24 weeks¹

forest-plot-showing-the-mean-difference-in-change-from-baseline-in-total-SGRQ-score-of-FF/UMEC/VI-(100/62.5/25)-versus-comparators-at-24-weeks.-A-box-is-highlighting-two-values-for-FF/UMEC/VI-versus-BUD/GLY/FOR-(320/18/9.6)-and-BUD/GLY/FOR-(160/18/9.6)-with-the-mean-differences-for-these-comparisons-being-minus-0.66-(95-percent-confidence-interval-minus-2.53-to-1.21)-and-minus-0.92-(95-percent-confidence-interval-minus-2.84-to-1.00)-respectively.-For-the-comparison-with-BUD/GLY/FOR-(320/18/9.6)-the-p-value-was-equal-to-0.4871.-For-the-comparison-with-BUD/GLY/FOR-(160/18/9.6)-the-p-value-was-equal-to-0.3490

Figure adapted with permission from Ismaila AS, et al. Adv Ther. 2022;39:3957-3978. Frequentist NMA FE model. BUD/GLY/FOR 320/18/9.6 BD is the licenced dose for COPD.²⁷

SGRQ responders: FF/UMEC/VI versus comparators at 12 weeks¹

forest-plot-showing-the- odds-ratio-for-SGRQ-responder-analysis-of-FF/UMEC/VI-(100/62.5/25)-versus-comparators-at-12-weeks

Figure adapted with permission from Ismaila AS, et al. Adv Ther. 2022;39:3957-3978. Frequentist NMA FE model.

Click here for details of the TDI and rescue medication use endpoints
Compared to the lung function, exacerbation and SGRQ endpoints, there were fewer trials available to include in the NMA for the TDI and rescue medication use endpoints.

TDI¹

5 trials reporting TDI data were included in the NMA.

FF/UMEC/VI demonstrated a greater improvement in TDI focal score at 24 weeks compared with UMEC + FF/VI and BUD/GLY/FOR (320/18/9.6) (non-significant).

Comparisons of FF/UMEC/VI versus comparators was only feasible at 24 weeks because of lack of data at weeks 12 and 52. No comparison of FF/UMEC/VI versus other triple therapies was feasible due to lack of data.

Rescue medication use¹

4 trials reporting rescue medication use data were included in the NMA.

At 24 weeks, FF/UMEC/VI demonstrated a statistically significant reduction in the use of rescue medication compared with BUD/ GLY/FOR (160/18/9.6), and a non-significant reduction in rescue medication use compared with BUD/GLY/FOR (320/18/9.6).

Comparisons of FF/UMEC/VI versus triple therapy comparators was only feasible at 24 weeks because of lack of data at weeks 12 and 52.

BUD, budesonide; FF, fluticasone furoate; FOR, formoterol; GLY, glycopyrronium; NMA, network meta-analysis; NS, non-significant; TDI, Transition Dyspnoea Index; UMEC, umeclidinium; VI, vilanterol.

The full publication is available here: https://pubmed.ncbi.nlm.nih.gov/35849317/

Continue your journey

NMA introduction

Comparing efficacy of triple therapies among patients with COPD

LEARN MORE

Summary

Summary of NMA class comparison results for FF/UMEC/VI versus triple and dual bronchodilator therapies.

LEARN MORE

Abbreviations

AUC, area under the curve; BD, twice daily; BDI, Baseline Dyspnoea Index; BDP, beclomethasone dipropionate; BUD, budesonide; CAT, COPD Assessment Test; CFB, change from baseline; CI, confidence interval; COPD, chronic obstructive pulmonary disease; CSR, clinical study report; EXT, extension; FE, fixed effect; FEV₁, forced expiratory volume in 1 second; FF, fluticasone furoate; FOR, formoterol; FP, fluticasone propionate; GLY, glycopyrronium bromide; ICS, inhaled corticosteroid; IND, indacaterol; IR, incidence rate; IRR, incidence rate ratio; ITC, indirect treatment comparison; ITT, intent-to-treat; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist; MITT, multiple-inhaler triple therapy; NA, not available; NMA, network meta-analysis; NS, non-significant; PBO, placebo; QD, once daily; RCT, randomised controlled trial; RE, random effect; SAL, salmeterol; SITT, single-inhaler triple therapy; SLR, systematic literature review; TDI, Transition Dyspnoea Index; TIO, tiotropium; UMEC, umeclidinium; VI, vilanterol.

References

Ismaila AS, et al. Adv Ther. 2022;39:3957-3978.
Ferguson GT, et al. Lancet Respir Med. 2018;6:747-758.
Lipson DA, et al. Am J Respir Crit Care Med. 2017;196:438-446.
Lipson DA, et al. N Engl J Med. 2018;378:1671-1680.
Bremner PR, et al. Respir Res. 2018;19:19.
Ferguson GT, et al. Respir Res. 2020;21:131.
Singh D, et al. Lancet. 2016;388:963-973.
Vestbo J, et al. Lancet. 2017;389:1919-1929.
TRISTAR clinical trial (NCT02467452). Available from https://clinicaltrials.gov/ct2/show/NCT02467452. Accessed 05 May 2022.
Rabe KF, et al. N Engl J Med. 2020;383:35-48.
Papi A, et al. Lancet. 2018;391:1076-1084.
Bansal S, et al. NPJ Prim Care Respir Med. 2021;31:29.
Bourbeau J, et al. Int J Chron Obstruct Pulmon Dis. 2021;16:499-517.
EU Clinical Trials Register. EudraCT number 2014-001487-35. Available from: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-001487-35/results. Accessed 9 June 2022.
European Medicines Agency. Guideline on clinical investigation of medicinal products in the treatment of chronic obstructive pulmonary disease (COPD). Available from https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-clinical-investigation-medicinal-products-treatment-chronic-obstructive-pulmonary-disease_en.pdf. Acessed June 2022.
Siler TM, et al. Respir Med. 2015;109:1155-1163.
Sousa AR, et al. NPJ Prim Care Respir Med. 2016;26:16031.
Siler TM, et al. Copd. 2016;13:1-10.
Lee SD, et al. Respirology. 2016;21:119-127.
Lee SD, et al. Respirology. 2016;21:119-127.
Welte T, et al. Am J Respir Crit Care Med. 2009;180:741-750.
Kerwin EM, et al. Respir Res. 2019;20:167.
Frith PA, et al. Thorax. 2015;70:519-527.
Aaron SD, et al. Ann Intern Med. 2007;146:545-555.
Hanania NA, et al. Respir Med. 2012;106:91-101.
Jung KS, et al. Respir Med. 2012;106:382-389.
Breztri Aerosphere US Prescribing information. Available from https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/212122s000lbl.pdf. Accessed 18 May 2022.

NX-GBL-UCV-WCNT-220011 | Date of preparation: November 2022

You are now leaving GSK’s website

NMA class comparison data in COPD

Key outcomes of interest¹

Methodology and networks of evidence¹

Click here to learn about methodological considerations

Click here to find out more about the SLR

Key SITT trials word cloud by population size^2-12

Click here for more information on key trials included in the NMA

Click here for more information on all the trials included in the NMA

Network of evidence informing analyses

Network of evidence informing annualised exacerbation analyses¹

Network of evidence informing trough FEV₁ analysis at 12 weeks¹

Network of evidence informing trough FEV₁ analysis at 24 weeks¹

Network of evidence informing SGRQ total score analysis at 12 weeks¹

Network of evidence informing SGRQ total score analysis at 24 weeks¹

Network of evidence informing SGRQ responders at 12 weeks¹

Results: Exacerbations and lung function

Annualised exacerbations: FF/UMEC/VI versus comparators for all studies¹

Annualised exacerbations: FF/UMEC/VI versus comparators for studies with ≥24 weeks of follow-up¹

Lung function: FF/UMEC/VI versus comparators at 12 weeks¹

Lung function: FF/UMEC/VI versus comparators at 24 weeks¹

Results: Health status

SGRQ total score: FF/UMEC/VI versus comparators at 12 weeks¹

SGRQ total score: FF/UMEC/VI versus comparators at 24 weeks¹

SGRQ responders: FF/UMEC/VI versus comparators at 12 weeks¹

Click here for details of the TDI and rescue medication use endpoints

Continue your journey

Abbreviations

References

Contact us

NMA class comparison data in COPD

Key outcomes of interest1

Methodology and networks of evidence1

Key SITT trials word cloud by population size2-12

Network of evidence informing analyses

Network of evidence informing annualised exacerbation analyses1

Network of evidence informing trough FEV1 analysis at 12 weeks1

Network of evidence informing trough FEV1 analysis at 24 weeks1

Network of evidence informing SGRQ total score analysis at 12 weeks1

Network of evidence informing SGRQ total score analysis at 24 weeks1

Network of evidence informing SGRQ responders at 12 weeks1

Results: Exacerbations and lung function

Annualised exacerbations: FF/UMEC/VI versus comparators for all studies1

Annualised exacerbations: FF/UMEC/VI versus comparators for studies with ≥24 weeks of follow-up1

Lung function: FF/UMEC/VI versus comparators at 12 weeks1

Lung function: FF/UMEC/VI versus comparators at 24 weeks1

Results: Health status

SGRQ total score: FF/UMEC/VI versus comparators at 12 weeks1

SGRQ total score: FF/UMEC/VI versus comparators at 24 weeks1

SGRQ responders: FF/UMEC/VI versus comparators at 12 weeks1

Continue your journey

Abbreviations

References

Contact us

Key outcomes of interest¹

Methodology and networks of evidence¹

Key SITT trials word cloud by population size^2-12

Network of evidence informing annualised exacerbation analyses¹

Network of evidence informing trough FEV₁ analysis at 12 weeks¹

Network of evidence informing trough FEV₁ analysis at 24 weeks¹

Network of evidence informing SGRQ total score analysis at 12 weeks¹

Network of evidence informing SGRQ total score analysis at 24 weeks¹

Network of evidence informing SGRQ responders at 12 weeks¹

Annualised exacerbations: FF/UMEC/VI versus comparators for all studies¹

Annualised exacerbations: FF/UMEC/VI versus comparators for studies with ≥24 weeks of follow-up¹

Lung function: FF/UMEC/VI versus comparators at 12 weeks¹

Lung function: FF/UMEC/VI versus comparators at 24 weeks¹

SGRQ total score: FF/UMEC/VI versus comparators at 12 weeks¹

SGRQ total score: FF/UMEC/VI versus comparators at 24 weeks¹

SGRQ responders: FF/UMEC/VI versus comparators at 12 weeks¹