Anti-inflammatory duration of action of fluticasone furoate/vilanterol trifenatate in asthma: a cross-over randomised controlled trial

Abstract

BackgroundFluticasone furoate/Vilanterol trifenatate (FF/VI) is an inhaled corticosteroid/long-acting beta-agonist combination with a prolonged bronchodilator duration of action. We characterised the time-course of onset and offset of airway anti-inflammatory action of FF/VI, as assessed by fraction of exhaled nitric oxide (FeNO), and compared this to the bronchodilator duration of action.MethodsA single-centre, randomised, double-blind, placebo-controlled, two-period, crossover study was undertaken in 28 steroid-naïve adults with asthma. Participants with an FEV1 ≥ 60% predicted, reversible airway disease, and FeNO > 40 ppb received FF/VI 100/25 mcg or placebo once daily for 14 days. FeNO and peak expiratory flow were measured twice-daily during treatment and during a 21-day washout period. FEV1 was measured for five days from treatment cessation. The primary outcome measure was FeNO change from baseline ratio for 21 days following treatment cessation.ResultsIn the 27 subjects who completed the study, median (range) baseline FeNO was 87 ppb (42–212). FF/VI 100/25 mcg reduced FeNO by day 3, ratio FF/VI versus placebo 0.72 (95% confidence interval 0.61–0.86) with the maximum reduction occurring at day 14, 0.32 (0.27–0.37). Following cessation of treatment FeNO remained suppressed for 18 days, ratio on day 18 0.77 (0.59–1.00), whereas improvements in FEV1 and peak flow were maintained for 3 to 4 days post-treatment.ConclusionsThe anti-inflammatory duration of action of FF/VI is consistent with the high glucocorticoid receptor affinity and long lung retention of fluticasone furoate. The anti-inflammatory effect of FF/VI was of greater duration than its bronchodilator effect in adults with mild asthma.Funding GlaxoSmithKline (201499).Trial registrationProspectively registered on ClinicalTrials.gov registry number NCT02712047.Electronic supplementary materialThe online version of this article (10.1186/s12931-018-0836-6) contains supplementary material, which is available to authorized users.

Current appraisal of single inhaler triple therapy in COPD

“… 18 , 19 The prolonged duration of lung retention with FF is evident in patients with asthma where FeNO remains suppressed for up to 18 days after stopping treatment with FF compared to up to 7 days after stopping FP. 20 , 21 It is unclear as to whether the more frequent exacerbating phenotype in IMPACT might in part explain the increased pneumonia risk, aside from the particular pharmacologic properties of FF. Interestingly the increased total and peripheral lung deposition associated with the extra fine formulation of BDP did not translate into an increased pneumonia risk in TRIBUTE.…”

Measuring and reporting treatment adherence: What can we learn by comparing two respiratory conditions?

“…Recent evidence indicates that asthma is forgiving to poor therapy adherence, and that it is possible to achieve similar levels of exacerbation reduction in mild asthma with less frequent doses of inhaled steroids than are typically prescribed 61 . Given that drug effects may persist for several days after administration, 62 asthma medications with longer durations of efficacy may be particularly forgiving 63–65 . Importantly, the same medication may also be eliminated at different rates in different people (known as “pharmacokinetic variability”), based on factors such as age, sex, smoking status and body size 66–68 …”

End‐point selection to determine the airway‐systemic ratio of inhaled corticosteroids in asthma

“…3 The anti-asthmatic response would inevitably be biased towards FF due to the consecutive dosing regimen, as there would have been appreciable airway accumulation of FF at steady state, given that we already know that FF suppresses an ICS responsive type 2 biomarker, namely fractional exhaled nitric oxide (FeNO), for 18 days after cessation. 4 This in turn would result in an appreciable carryover effect of FF between weekly dose escalation which would not be seen with BUD as this has much shorter lung retention, and would further confound meaningful interpretation of any doseresponse effect.…”