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Effects of low-versus high-dose fluticasone propionate/formoterol fumarate combination therapy on AMP challenge in asthmatic patients: A double-blind, randomised clinical trial.

Kanniess, Frank; Diamant, Zuzana LU and Lomax, Mark (2016) In Pulmonary Pharmacology & Therapeutics 37. p.65-72
Abstract
BACKGROUND:



The dose-response relationship between two dose levels of fluticasone/formoterol (flutiform®, 100/10 μg and 500/20 μg) was evaluated in asthmatic patients. Non-invasive inflammatory markers were used including adenosine monophosphate (AMP) challenge (primary endpoint), and sputum eosinophils and fractional exhaled nitric oxide (FeNO) (secondary endpoints).

METHODS:



Patients aged ≥18 years with forced expiratory volume in 1 second (FEV1) ≥60% predicted and who required a dose of <60 mg AMP to elicit a 20% drop in FEV1 (AMP PD20) were randomised in this incomplete block, crossover study to receive 2 of 3 treatments b.i.d.: fluticasone/formoterol 500/20 μg (high dose), 100/10 μg... (More)
BACKGROUND:



The dose-response relationship between two dose levels of fluticasone/formoterol (flutiform®, 100/10 μg and 500/20 μg) was evaluated in asthmatic patients. Non-invasive inflammatory markers were used including adenosine monophosphate (AMP) challenge (primary endpoint), and sputum eosinophils and fractional exhaled nitric oxide (FeNO) (secondary endpoints).

METHODS:



Patients aged ≥18 years with forced expiratory volume in 1 second (FEV1) ≥60% predicted and who required a dose of <60 mg AMP to elicit a 20% drop in FEV1 (AMP PD20) were randomised in this incomplete block, crossover study to receive 2 of 3 treatments b.i.d.: fluticasone/formoterol 500/20 μg (high dose), 100/10 μg (low dose) or placebo, during 2 periods of 28±3 days each, separated by 2-3 weeks. AMP challenges were performed pre-dose and 12 hours after last dose at the end of each treatment period. A series of post hoc analyses were performed only in patients allocated to both fluticasone/formoterol doses, who completed the study and had evaluable AMP PD20 data for both treatments ("fluticasone/formoterol subgroup"). Changes in AMP PD20 FEV1, percentage sputum eosinophils and FeNO levels (day 1 vs day 28) between treatments were compared by an analysis of covariance (ANCOVA).

RESULTS:



Sixty-two patients were randomised and 46 completed the study. Fifteen patients received both high- and low-dose fluticasone/formoterol (post hoc subgroup). The difference in AMP PD20 for the overall population was not statistically significant between high- and low-dose fluticasone/formoterol (LS mean fold difference: 1.3; p=0.489), although both dose levels were superior to placebo: high-dose vs placebo LS mean fold difference: 4.4, p<0.001; low-dose vs placebo LS mean fold difference: 3.5, p<0.001. In the post hoc subgroup, the difference in AMP PD20 between the doses was statistically significant in favour of the high-dose (LS mean fold difference: 2.4, p=0.012). Other inflammatory parameters (sputum eosinophil counts and FeNO) showed small differences and statistically non-significant changes between high- and low-dose fluticasone/formoterol.

CONCLUSIONS:



A significant dose-response was found between low- and high-dose fluticasone/formoterol in the post hoc subgroup (patients who received both doses), but not in the overall population, with the higher dose demonstrating a greater reduction in airway responsiveness to AMP. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Pulmonary Pharmacology & Therapeutics
volume
37
pages
65 - 72
publisher
Elsevier
external identifiers
  • pmid:26912209
  • scopus:84960173056
  • wos:000375516400010
ISSN
1522-9629
DOI
10.1016/j.pupt.2016.02.003
language
English
LU publication?
yes
id
699b54c8-9b2a-474e-ac29-6a0cc0954aec (old id 8821730)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26912209?dopt=Abstract
date added to LUP
2016-03-02 09:40:40
date last changed
2017-04-03 11:05:39
@article{699b54c8-9b2a-474e-ac29-6a0cc0954aec,
  abstract     = {BACKGROUND:<br/><br>
<br/><br>
The dose-response relationship between two dose levels of fluticasone/formoterol (flutiform®, 100/10 μg and 500/20 μg) was evaluated in asthmatic patients. Non-invasive inflammatory markers were used including adenosine monophosphate (AMP) challenge (primary endpoint), and sputum eosinophils and fractional exhaled nitric oxide (FeNO) (secondary endpoints).<br/><br>
METHODS:<br/><br>
<br/><br>
Patients aged ≥18 years with forced expiratory volume in 1 second (FEV1) ≥60% predicted and who required a dose of &lt;60 mg AMP to elicit a 20% drop in FEV1 (AMP PD20) were randomised in this incomplete block, crossover study to receive 2 of 3 treatments b.i.d.: fluticasone/formoterol 500/20 μg (high dose), 100/10 μg (low dose) or placebo, during 2 periods of 28±3 days each, separated by 2-3 weeks. AMP challenges were performed pre-dose and 12 hours after last dose at the end of each treatment period. A series of post hoc analyses were performed only in patients allocated to both fluticasone/formoterol doses, who completed the study and had evaluable AMP PD20 data for both treatments ("fluticasone/formoterol subgroup"). Changes in AMP PD20 FEV1, percentage sputum eosinophils and FeNO levels (day 1 vs day 28) between treatments were compared by an analysis of covariance (ANCOVA).<br/><br>
RESULTS:<br/><br>
<br/><br>
Sixty-two patients were randomised and 46 completed the study. Fifteen patients received both high- and low-dose fluticasone/formoterol (post hoc subgroup). The difference in AMP PD20 for the overall population was not statistically significant between high- and low-dose fluticasone/formoterol (LS mean fold difference: 1.3; p=0.489), although both dose levels were superior to placebo: high-dose vs placebo LS mean fold difference: 4.4, p&lt;0.001; low-dose vs placebo LS mean fold difference: 3.5, p&lt;0.001. In the post hoc subgroup, the difference in AMP PD20 between the doses was statistically significant in favour of the high-dose (LS mean fold difference: 2.4, p=0.012). Other inflammatory parameters (sputum eosinophil counts and FeNO) showed small differences and statistically non-significant changes between high- and low-dose fluticasone/formoterol.<br/><br>
CONCLUSIONS:<br/><br>
<br/><br>
A significant dose-response was found between low- and high-dose fluticasone/formoterol in the post hoc subgroup (patients who received both doses), but not in the overall population, with the higher dose demonstrating a greater reduction in airway responsiveness to AMP.},
  author       = {Kanniess, Frank and Diamant, Zuzana and Lomax, Mark},
  issn         = {1522-9629},
  language     = {eng},
  month        = {02},
  pages        = {65--72},
  publisher    = {Elsevier},
  series       = {Pulmonary Pharmacology & Therapeutics},
  title        = {Effects of low-versus high-dose fluticasone propionate/formoterol fumarate combination therapy on AMP challenge in asthmatic patients: A double-blind, randomised clinical trial.},
  url          = {http://dx.doi.org/10.1016/j.pupt.2016.02.003},
  volume       = {37},
  year         = {2016},
}