Bousquette.qxp 11/8/09 2:34 pm Page 10
Asthma
Efficacy and Safety of Combination Inhaled Corticosteroids/
Long-acting β
2
-adrenergic Agonists in Single Inhaler Devices for Asthma
Jean Bousquet
Professor of Respiratory Medicine, University of Montpellier
Abstract
Although inhaled corticosteroids (ICS) have proven benefits in the treatment of asthma, some patients are not able to achieve adequate
control over their asthmatic symptoms with ICS alone. Current guidelines recommend that in these patients, a long-acting β
2
-adrenergic
agonist (LABA), a leukotriene receptor antagonist (LTRA) or theophylline is added to the regimen. The complementary effects of ICS and LABAs
compared with ICS alone led to the introduction of both components into a single inhaler device. Combination ICS/LABA therapy can control
asthma symptoms using lower doses of ICS compared with ICS alone. This is turn may allow patients to avoid becoming overly reliant on their
LABA or short-acting β
2
-agonist (SABA) treatments at the expense of the ICS drug, which may alleviate concerns over LABA use in the absence
of a regular background steroid. Studies have established the efficacy of fixed doses of the ICS budesonide plus the LABA formoterol, and the
ICS fluticasone plus the LABA salmeterol, in reducing the rate of exacerbations and improving asthma symptoms and lung function.
Furthermore, adjustable- and fixed-dose budesonide plus formoterol and fixed-dose fluticasone plus salmeterol have been shown to be well-
tolerated with no apparent unprecedented safety concerns. More real-life studies are needed to understand where adjustable-dose
budesonide plus formoterol stands in terms of efficacy compared with fixed doses of the ICS plus LABA combination therapies.
Keywords
Inhaled corticosteroids (ICS), long-acting β
2
-adrenergic agonist (LABA), leukotriene receptor antagonist (LTRA), theophylline, asthma, combination,
budesonide, formoterol, fluticasone, salmeterol
Disclosure: The author has no conflicts of interest to declare.
Received: 13 November 2008 Accepted: 2 July 2009
Correspondence: Jean Bousquet, Clinique des Maladies Respiratoires, Hôpital Arnaud de Villeneuve, Centre Hospitalier Universitaire, 371, Avenue du Doyen Gaston Giraud,
jean.bousquet@orange.fr
The anti-inflammatory properties of inhaled corticosteroids (ICS) are (Symbicort
®
, AstraZeneca), fluticasone plus salmeterol (Seretide/
beneficial in the treatment of asthma, a disorder characterised by Advair
®
, GlaxoSmithKline) and formoterol plus beclomethasone
chronic inflammation of the airways. However, some patients are (Foster
®
, Chiesi). Clinical studies have attributed high efficacy to these
not able to achieve adequate control over their asthmatic symptoms combinations in providing early and sustained improvements in
with ICS alone.
1
In these patients, the addition of a long-acting β
2
- asthma control in patients who are not fully responsive to ICS alone.
13–16
adrenergic agonist (LABA), a leukotriene receptor antagonist (LTRA) However, the constituent components of the two combination
or theophylline is recommended.
2,3
More specifically, in patients ≥12 preparations have differing properties: the onset of action of
years of age requiring more than low-dose ICS alone to control formoterol differs from that of salmeterol,
17
the dose–response
asthma, a combination of ICS and LABAs is the recommended first- relationship differs between formoterol and salmeterol
18
and
line therapeutic option.
2,4
The complementary effects of ICS and differences have been reported for budesonide and fluticasone.
19
This
LABAs compared with ICS alone
5,6
have led to the introduction of article will review the evidence comparing the efficacy and safety of
both components into a single inhaler device. Such combination budesonide plus formoterol in fixed doses and adjustable doses with
products are not only convenient, but also simpler; these factors that of fixed-dose fluticasone plus salmeterol.
have been proposed to be advantageous in terms of maintaining
patient adherence to treatment compared with multiple Fixed-dose Regimens of Inhaled
medications.
7,8
Combination therapy can also control asthma using Corticosteroid/Long-acting β
2
-adrenergic
lower doses of ICS compared with ICS alone,
9,10
which may allow Agonist Combination Preparations
patients to avoid becoming overly reliant on their LABA or short- Efficacy
acting β
2
-agonist (SABA) treatments at the expense of ICS drugs. In Studies have shown similar rates of efficacy and safety between
doing so, this may alleviate concerns over LABA use in the absence fixed doses of budesonide plus formoterol dry-powder inhaler (DPI)
of a regular background steroid.
11,12
and fluticasone plus salmeterol DPI.
20,21
In an open-label randomised
study by Aalbers et al., patients exhibited similar odds ratios (ORs)
Currently, three combination preparations are commercially available of achieving a week of well-controlled asthma for fixed-dose
for the treatment of persistent asthma: budesonide plus formoterol fluticasone plus salmeterol DPI 250/50µg one inhalation twice daily
10 © TOUCH BRIEFINGS 2009
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68