INTREPID: Clinical Effectiveness of ONCE-Daily Single-Inhaler Fluticasone Furoate/Umeclidinium/Vilanterol Versus Multiple-Inhaler Triple Therapy in Usual Clinical Practice

Rationale: In COPD use of multiple inhalers is associated with more errors and worse adherence than single-inhaler regimens and could result in worse outcomes. Real-world effectiveness data on single-inhaler vs. multiple-inhaler regimens on health status in COPD are lacking.

Methods: INTREPID is a randomized, open-label, phase IV study that evaluated the impact of single-inhaler triple therapy vs. multiple-inhaler triple therapy (MITT) on health status, measured using the COPD Assessment Test (CAT), over 24 weeks in usual clinical care in five European countries who had continuously received non-ELLIPTA maintenance therapy (MITT or dual therapy with documented clinical indication for step-up to triple therapy) for ≥ 16 weeks prior to randomization, CAT score ≥ 10 and ≥ 1 moderate/severe exacerbation in the prior 3 years. Patients were randomized to Fluticasonfuroat/Umeclidinium/Vilanterol (FF/UMEC/VI) 100/62.5/25 µg via ELLIPTA or any ICS+LAMA+LABA combination in non-ELLIPTA devices by clinicianʼs choice for 24 weeks. Primary endpoint was the proportion of CAT responders (≥ 2-unit decrease in score from baseline) at Week 24. Secondary endpoints in a subset were change from baseline in forced expiratory volume in 1 second (FEV₁) and proportion of patients making ≥ 1 critical error in inhalation technique at 24 weeks. Safety was evaluated descriptively.

Results: The ITT-population comprised 3092 patients (FF/UMEC/VI N = 1545; MITT N = 1547). The odds of being a CAT responder at Week 24 were statistically significantly greater with FF/UMEC/VI than MITT (odds ratio 1.31; p < 0.001). At Week 24 FF/UMEC/VI improved FEV₁ change from baseline by 50 mL more than MITT (p < 0.001). In total 38/653 FF/UMEC/VI-treated patients (6%) and 7/230 MITT-treated patients (3%) made ≥ 1 critical error in inhalation technique at Week 24 (p = 0.103). Safety profiles were similar between the cohorts, with no new safety findings. On-randomized treatment pneumonia serious adverse events occurred in 26 (2%) and 30 (2%) patients in the FF/UMEC/VI and MITT cohorts, respectively.

Conclusions: In usual clinical care, treatment with single-inhaler FF/UMEC/VI results in significantly more patients with health status improvements and greater lung function benefit vs. MITT, with similar safety profiles.

Tab. 1 

ITT Population	FF/UMEC/VI (N = 1545)	MITT (N = 1547)	FF/UMEC/VI versus MITT
Characteristics at screening
Randomized prior medication use starta, n (%)
ICS+LAMA+LABA	1240 (80)	1240 (80)	–
ICS+LABA	120 (8)	123 (8)
LABA+LAMA	185 (12)	184 (12)
CAT score, mean (SD)	n = 1543 20.8 (6.76)	n = 1547 20.5 (6.62)	–
Primary endpoint			Odds ratio (95% CI); p-value
CAT response status, n (%)	n = 1539	n = 1543	1.31 (1.13, 1.51); p < 0.001
Responders	731 (47)	616 (40)
Non-responders	756 (49)	835 (54)
Patients with imputed CAT score	52 (3)	92 (6)
FEV1 Population	FF/UMEC/VI (N = 910)	MITT (N = 904)	FF/UMEC/VI versus MITT
Characteristics at screening
Post-bronchodilator FEV1, mL, mean (SD)	n = 825 1474 (563.3)	n = 827 1462 (584.0)	–
Secondary endpoint			Treatment difference (95% CI); p-value
Least square mean change from baseline in FEV1 at week 24, mL (95% CI)	n = 691 77 (57, 98)	n = 675 28 (6, 49)	50 (26, 73); p < 0.001
Critical Error Population	FF/UMEC/VI (N = 691)	MITT (N = 267)	FF/UMEC/VI versus MITT
Secondary endpoint			Odds ratio (95% CI); p-value
Paitents with ≥ 1 critical error at week 24, n (%)	n = 653 38 (6)	n = 230 7 (3)	1.99 (0.87, 4.53); p = 0.103
Patients with no critical errors at week 24, n (%)	615 (94%)	223 (97%)

 

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Publication History

Article published online:
30 April 2021