Budesonide/formoterol used for both maintenance and reliever therapy has been shown to benefit patients with persistent asthma. We evaluated patient satisfaction and asthma control among Malaysian patients prescribed budesonide/formoterol as single maintenance and reliever therapy in a real-life clinical practice.
Adult patients diagnosed with partially controlled or uncontrolled asthma were recruited in a 6-month, prospective, open-label study involving ten hospital-based chest clinics in Malaysia. Patients were prescribed one or two inhalations of budesonide/formoterol Turbuhaler (160/4.5 μg per inhalation) twice daily as maintenance therapy and additional inhalation as reliever therapy. Maintenance doses were decided by physicians based on Global Initiative for Asthma-defined treatment objectives. The primary outcome measure was the change in mean Satisfaction with Asthma Treatment Questionnaire (SATQ) scores from baseline to an average of 3 months and 6 months. Secondary outcome was the change in mean Asthma Control Questionnaire 5-item version (ACQ-5) scores from baseline to an average of 3 months and 6 months and the proportion of patients achieving the minimum clinically important difference.
Of 201 eligible patients recruited, 195 completed the study. Overall, SATQ mean (standard deviation) score was significantly improved from 5.1 (0.76) at baseline to 5.5 (0.58) (P < 0.001). The increase was observed in all domains of SATQ and had occurred at 3 months for most patients. ACQ-5 mean (standard deviation) score was significantly reduced from 2.2 (1.13) at baseline to 1.2 (0.95) (P < 0.001). A total of 132 (67.7.1%) patients had achieved the minimal clinically important difference (≥0.5) of ACQ-5 scores at study end.
In a nationwide study, budesonide/formoterol maintenance and reliever therapy achieved greater patient satisfaction and better asthma control compared with previous conventional asthma regimes among Malaysian patients treated in a real-life practice setting. Such an approach may represent an important treatment alternative for our local patients with persistent asthma.
asthma; asthma control; Malaysia; maintenance and reliever therapy; satisfaction; Symbicort; budesonide/formoterol
To study the effectiveness and safety of budesonide/formoterol (Symbicort®) Maintenance And Reliever Therapy (Symbicort SMART®, AstraZeneca, Södertalje, Sweden), a simplified management approach with one inhaler compared with conventional best practice (CBP) with multiple inhalers in patients with persistent asthma.
Open-label randomised controlled parallel group trial, 6-month treatment.
A total of 908 patients ≥ 12 years of age, with persistent asthma receiving treatment with inhaled corticosteroids (ICS), either alone or in conjunction with long-acting β2-agonist.
Main outcome measures:
Time to first severe asthma exacerbation and number of severe asthma exacerbations.
No difference between groups was seen in time to first severe exacerbation (p = 0.75). Exacerbation rates were low in both groups. A total of 12 patients in the Symbicort SMART® group experienced a total of 14 severe asthma exacerbations, and 19 patients in the CBP group experienced a total of 25 severe asthma exacerbations (annual rate 0.07 vs. 0.13 p = 0.09). The mean daily dose of ICS expressed in BDP equivalent was significantly lower in the Symbicort SMART® group (including as-needed use) vs. in the CBP group (749 μg vs. 1059 μg; p < 0.0001). Mean scores in Asthma Control Questionnaire, 5 question version improved significantly in the SMART group compared with the CBP group (p = 0.0026). Symbicort SMART and CBP were equally well tolerated.
The mean drug cost/patient/month was significantly lower for the patients in the Symbicort SMART group compared with patients receiving CBP (51.3 € vs. 66.5 €; p < 0.0001).
In Belgian patients, a simplified regimen using budesonide/formoterol maintenance and reliever therapy was at least as effective at improving clinical control compared with CBP with a significantly lower ICS dose and significantly lower drug costs.
Divergent strategies have emerged for the management of severe asthma. One strategy utilises high and fixed doses of maintenance treatment, usually inhaled corticosteroid/long-acting β2-agonist (ICS/LABA), supplemented by a short-acting β2-agonist (SABA) as needed. Alternatively, budesonide/formoterol is used as both maintenance and reliever therapy. The latter is superior to fixed-dose treatment in reducing severe exacerbations while achieving similar or better asthma control in other regards. Exacerbations may be reduced by the use of budesonide/formoterol as reliever medication during periods of unstable asthma. We examined the risk of a severe exacerbation in the period after a single day with high reliever use.
Episodes of high reliever use were quantified and exacerbations occurring post-index day with these episodes were examined post hoc in two double-blind studies comparing the efficacy and safety of budesonide/formoterol maintenance and reliever therapy (Symbicort SMART™, Turbuhaler®) 160/4.5 μg twice daily plus as needed with similar or higher maintenance doses of ICS/LABA plus SABA or formoterol.
Budesonide/formoterol maintenance and reliever therapy significantly reduced the risk of episodes of high reliever use (>6 inhalations/day) vs. all alternative ICS/LABA regimens. With conventional fixed-dose treatment the need for exacerbation treatment within 21 days ranged from 6.0–10.1% of days post-index for all regimens compared with 2.5–3.4% of days with budesonide/formoterol maintenance and reliever therapy.
Budesonide/formoterol maintenance and reliever therapy reduces the incidence of high reliever episodes and the exacerbation burden immediately following these episodes vs. alternative ICS/LABA plus SABA regimens at up to double the maintenance dose of ICS.
These studies do not have registration numbers as they were conducted before clinical trial registration was required
Asthma; Asthma in primary care
Symbicort SMART® (Symbicort Maintenance and Reliever Therapy) represents a new and unique way of treating patients with moderate-to-severe asthma, ie, those patients who require combination treatment with an inhaled corticosteroid and a long-acting inhaled β2-agonist. Symbicort SMART enables patients to use only one inhaler, the budesonide-formoterol combination inhaler, for both maintenance and reliever therapy. The maintenance dose is adjustable, but should be a minimum of two doses per day which can be administered as two doses once daily or as one dose twice daily. It is important that the temporary reliever medication includes not only a bronchodilator but also an antiinflammatory drug because worsening of asthma includes not only more airway narrowing, but also an increase in airway inflammation. The Symbicort SMART concept therefore ensures that the patient gets an antiinflammatory drug at the time of the first signs of asthma worsening. Clinical results show that Symbicort SMART prolongs the time to the first severe asthma exacerbation, reduces the rate of exacerbations, and maintains day-to-day asthma control at a reduced load of corticosteroids (inhaled plus systemic) when compared with higher fixed maintenance doses of combination inhalers. Symbicort SMART consequently offers a more effective and simple approach to asthma management for physicians and patients. Symbicort SMART is also easier for the patient as only one inhaler is required. The positive results with Symbicort SMART can be explained by the early as-needed use on the inhaled corticosteroid component, which puts out the early flames of inflammation, together with the interaction between the β2-agonist, formoterol, and the inhaled corticosteroid, budesonide.
asthma control; combination therapy; inhaled corticosteroid; long-acting β2-agonist; Symbicort SMART® (Symbicort Maintenance and Reliever Therapy)
The use of a combination inhaler containing budesonide and formoterol as both maintenance and quick relief therapy (SMART) has been recommended as an improved method of using inhaled corticosteroid/long-acting β agonist (ICS/LABA) therapy. Published double-blind trials show that budesonide/formoterol therapy delivered in SMART fashion achieves better asthma outcomes than budesonide monotherapy or lower doses of budesonide/formoterol therapy delivered in constant dosage. Attempts to compare budesonide/formoterol SMART therapy with regular combination ICS/LABA dosing using other compounds have been confounded by a lack of blinding and unspecified dose adjustment strategies. The asthma control outcomes in SMART-treated patients are poor; it has been reported that only 17.1% of SMART-treated patients are controlled. In seven trials of 6–12 months duration, patients using SMART have used quick reliever daily (weighted average 0.92 inhalations/day), have awakened with asthma symptoms once every 7–10 days (weighted average 11.5% of nights), have suffered asthma symptoms more than half of days (weighted average 54.0% of days) and have had a severe exacerbation rate of one in five patients per year (weighted average 0.22 severe exacerbations/patient/year). These poor outcomes may reflect the recruitment of a skewed patient population. Although improvement from baseline has been attributed to these patients receiving additional ICS therapy at pivotal times, electronic monitoring has not been used to test this hypothesis nor the equally plausible hypothesis that patients who are non-compliant with maintenance medication have used budesonide/formoterol as needed for self-treatment of exacerbations. Although the long-term consequences of SMART therapy have not been studied, its use over 1 year has been associated with significant increases in sputum and biopsy eosinophilia. At present, there is no evidence that better asthma treatment outcomes can be obtained by moment-to-moment symptom-driven use of ICS/LABA therapy than conventional physician-monitored and adjusted ICS/LABA therapy.
Budesonide; formoterol; compliance; asthma control; exacerbation; study design; asthma; asthma guidelines; asthma pharmacology; perception of asthma/breathlessness
The long-acting β2-agonist (LABA) formoterol has an onset of effect comparable to that of salbutamol. Consequently, the combination of formoterol and budesonide in one inhaler, approved for maintenance use, can potentially be used for reliever therapy. This study compared the onset of relief from induced bronchospasm with a single dose of budesonide/formoterol versus standard salbutamol therapy in patients with asthma.
In this randomised, double-blind, placebo-controlled, cross-over study, 32 patients with asthma underwent a methacholine provocation test leading to a fall in forced expiratory volume in 1 second (FEV1) of ≥30% at enrolment (Visit 1) and three subsequent study visits (Visits 2–4). Immediately after each provocation at Visits 2–4, patients received one of three test treatments: one inhalation of budesonide/formoterol 160/4.5 μg (via Turbuhaler®), two inhalations of salbutamol 100 μg (via a pressurised metered-dose inhaler [pMDI]) or placebo. All patients received each of the test treatments in a randomised order, after separate methacholine provocations. The effect of treatment on FEV1 and breathlessness (using the Borg scale) was measured at 1, 3, 5, 10, 15, 20, 25 and 30 minutes after test treatment.
Following methacholine provocation, Borg score increased from a baseline value of below 0.5 to 3.03, 3.31 and 3.50 before treatment with budesonide/formoterol, salbutamol and placebo, respectively. Budesonide/formoterol and salbutamol reversed methacholine-induced dyspnoea (breathlessness) rapidly. At 1 minute after inhalation, statistically significant decreases in Borg score were observed for budesonide/formoterol and salbutamol (p = 0.0233 and p < 0.0001, respectively, versus placebo), with similar rapid increases in FEV1 (both active treatments p < 0.0001 versus placebo). The median time to 50% recovery in Borg score after methacholine provocation was 3 minutes with budesonide/formoterol, 2 minutes with salbutamol and 10 minutes with placebo. All treatments and procedures were well tolerated.
Single doses of budesonide/formoterol and salbutamol both provided rapid relief of dyspnoea and reversal of severe airway obstruction in patients with asthma with experimentally induced bronchoconstriction. The perception of relief, as confirmed by objective lung function assessment, provides evidence that budesonide/formoterol can be used as reliever medication in asthma.
Current national and international asthma guidelines recommend treatment of children with asthma towards achieving and maintaining asthma control. These guidelines provide more stringent recommendations to increase therapy for patients with uncontrolled asthma in order to reduce asthma-related morbidity and mortality. Newer combination agents such as budesonide and formoterol have been shown to be safe and effective in treatment of asthma in children. Use of long-term controller agents like this in combination with improved compliance and treatment of co-morbid conditions have been successful in this endeavor. This review discusses control of pediatric asthma with focus on the use of budesonide in combination with formoterol.
asthma; control; children; budesonide; formoterol; long-term
Asthma’s cost-effectiveness is a major consideration in the evaluation of its treatment options. Our objective was to perform a systematic review of the cost-effectiveness of asthma medications.
We performed a systematic search of MEDLINE, EMBASE, CINAHL, Cochrane Database of Systematic Reviews, OHE-HEED, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Health Technology Assessments Database, NHS Economic Evaluation Database, and Web of Science and reviewed references from key articles between 1990 and Jan 2008.
A total of 49 RCTs met the inclusion criteria. Maintenance therapy with inhaled corticosteroids was found to be very cost-effective and in uncontrolled asthmatics patients currently being treated with ICS, the combination of an ICS/LABA represents a safe, cost-effective treatment. The simplified strategy using budesonide and formoterol for maintenance and reliever therapy was also found to be as cost-effective as salmeterol/fluticasone plus salbutamol. Omalizumab was found to be cost-effective. An important caveat with regard to the published literature is the relatively high proportion of economic evaluations which are funded by the manufacturers of specific drug treatments.
Future studies should be completed independent of industry support and ensure that the comparator arms within studies should include dosages of drugs that are equivalent.
asthma; medication; cost-effectiveness; cost of illness; economic costs
This study investigated the rapid onset of bronchodilation effect and compared lung function changes following budesonide/formoterol (Symbicort Turbuhaler®) inhalation in Chinese patients with moderate-severe chronic obstructive pulmonary disease (COPD) and bronchial asthma.
In this open-label, parallel-group clinical study, patients eligible for study were divided into COPD group (n=62, mean age 68.16±8.75 years) and asthma group (n=30, mean age 45.80±12.35 years). Lung function tests (include FEV1, FVC, FEV1/FVC, and IC) were performed at baseline (t=0 min time point, value before inhalation of budesonide/formoterol), and then eligible patients received two inhalations of budesonide/formoterol (160/4.5 μg). Lung function tests were reassessed at t=3, 10 and 30 min time point. The primary end-point was lung function change 3 min after drug inhalation, and the secondary end-points were comparison of the gas flow rate (ΔFEV1) and volume responses (ΔFVC, ΔIC) between COPD and asthma patients after inhalation of budesonide/formoterol.
Compared with the baseline, all patients significantly improved their lung function (included FEV1, FVC, FEV1/FVC, and IC) at 3 min (P<0.05). Greater bronchodilation efficacy was found in the asthma group compared with the COPD group (P<0.05). In the asthmatic patients, the curves of FEV1, FVC, FEV1/FVC, IC, showed improvement with an ascending trend at all time points from 3 to 30 min. Whereas in the COPD patients, only the curves of FEV1, FVC, IC showed similar pattern. We found that ΔFVC was significantly higher than ΔFEV1 in both groups (P<0.05), but no significant difference between ΔIC and ΔFEV1 (P>0.05). Compared with COPD group, asthma group had higher level of ΔFEV1 and ΔIC (P<0.05), but no significant difference for ΔFVC can be found.
Budesonide/formoterol has a fast onset of bronchodilation effect in patients with moderate-severe COPD and asthma. Greater efficacy was found in the asthma group compared with the COPD group. The gas flow rate and volume responses in patients with COPD differ from those with asthma after inhalation of Budesonide/formoterol.
Budesonide/formoterol; chronic obstructive pulmonary disease; bronchial asthma; lung function test
The budesonide/formoterol combination is successfully used for fast relief of asthma symptoms in addition to its use as maintenance therapy. The temporarily increased corticosteroid dose during increasing inhaler use for symptom relief is likely to suppress any temporary increase in airway inflammation and may mitigate or prevent asthma exacerbations. The relative contribution of the budesonide and formoterol components to the improved asthma control is unclear.
The acute protective effect of inhaled budesonide was tested in a model of temporarily increased airway inflammation with repeated indirect airway challenges, mimicking an acute asthma exacerbation. A randomised, double-blind, cross-over study design was used. Asthmatic patients (n = 17, mean FEV1 95% of predicted) who previously demonstrated a ≥30% fall in forced expiratory volume in 1 second (FEV1) after inhaling adenosine 5'-monophosphate (AMP), were challenged on four consecutive test days, with the same dose of AMP (at 09:00, 12:00 and 16:00 hours). Within 1 minute of the maximal AMP-induced bronchoconstriction at 09:00 hours, the patients inhaled one dose of either budesonide/formoterol (160/4.5 μg), formoterol (4.5 μg), salbutamol (2 × 100 μg) or placebo. The protective effects of the randomised treatments were assessed by serial lung function measurements over the test day.
In the AMP provocations at 3 and 7 hours after inhalation, the budesonide/formoterol combination provided a greater protective effect against AMP-induced bronchoconstriction compared with formoterol alone, salbutamol and placebo. In addition all three active treatments significantly increased FEV1 within 3 minutes of administration, at a time when inhaled AMP had induced the 30% fall in FEV1.
A single dose of budesonide/formoterol provided a greater protective effect against inhaled AMP-induced bronchoconstriction than formoterol alone, both at 3 and at 7 hours after inhalation. The acute protection against subsequent bronchoconstrictor stimuli such as inhaled AMP and the rapid reversal of airway obstruction supports the use of budesonide/formoterol for both relief and prevention in the treatment of asthma.
ClinicalTrials.gov number NCT00272753
The aim of this study was to assess the responsiveness of the asthma control test (ACT) to detect changes at the initiation of therapy and its utilization in the initiation of asthma treatment.
This study was designed as a randomized clinical trial conducted in a primary care setting. The subjects were asthma patients who had not received controller therapy for at least two months. The patients were randomized into two groups: The Saudi Initiative for Asthma (SINA) group and the Global Initiative for Asthma (GINA) group. Treatment in the SINA group was initiated at step1 when the ACT scores ≥ 20, step 2 when the score between16-19, and step 3 when the score < 16 began at step 3. The GINA group patients were started on step 2 when they had persistent asthma symptoms or step 3 when they had severely uncontrolled disease.
Forty-five patients were analyzed in each group. The improvement in ACT score after treatment initiation was significantly higher when the SINA approach was used (2.9 in the SINA group compared to 1.7 in the GINA group (p = 0.04)). The improvement in FEV1 was 5.8% in the SINA group compared to 3.4% in the GINA group (p = 0.46). The number of patients who achieved asthma control at the follow-up visit and required no treatment adjustment was 33 (73.3%) in the SINA group and 27 (60%) in the GINA group (p = 0.0125).
The ACT was responsive to change at the initiation of asthma treatment and was useful for the initiation of asthma treatment.
Trial Registration number
Asthma; Asthma control test; Guidelines; Global initiative for asthma; Saudi initiative for asthma; Control
Symptom control in patients with moderate to severe persistent asthma is essential to reduce the significant morbidity associated with the disease. Poor adherence to controller medications has been identified as a major contributing factor to the high level of uncontrolled asthma. This review examines patient perspectives on, and preferences for, controller medications (inhaled corticosteroid and long-acting β2-agonist combinations [ICS/LABA]), and how this may affect adherence to therapy. Fluticasone/salmeterol and budesonide/formoterol, the currently available ICS/LABA combination products, have similar efficacy and tolerability based on a recent meta-analysis of asthma trials. Adherence is higher with the combination ICS/LABAs than when the components are administered separately. Investigations into patient preferences for desirable attributes of asthma medications indicate that an effective reliever with a fast onset and long duration of action is preferred and may lead to improved adherence. This rapid onset of effect was perceived and highly valued in patient surveys, and was associated with greater patient satisfaction. Thus, future research should be directed at therapy that offers both anti-inflammatory activity and a rapid onset of bronchodilator effect. To further improve patient adherence and treatment outcome, the effect of these characteristics as well as other factors on adherence should also be investigated.
budesonide/formoterol; fluticasone/salmeterol; adherence; onset of effect; patient satisfaction
Conventionally, a nebulized short-acting β-2 agonist like salbutamol is often used as the reliever in acute exacerbations of asthma. However, recent worldwide respiratory outbreaks discourage routine use of nebulization. Previous studies have shown that combined budesonide/formoterol (Symbicort®, AstraZeneca) is effective as both a maintenance and reliever anti-asthmatic medication.
We performed a randomized, open-label study from March until August 2011 to compare the bronchodilatory effects of Symbicort® vs. nebulized salbutamol in acute exacerbation of mild to moderate asthmatic attack in an emergency department. Initial objective parameters measured include the oxygen saturation, peak expiratory flow rate (PEFR) and respiratory rate. During clinical reassessment, subjective parameters [i.e., Visual Analog Scale (VAS) and 5-point Likert scale of breathlessness] and the second reading of the objective parameters were measured. For the 5-point Likert scale, the patients were asked to describe their symptom relief as 1, much worse; 2, a little worse; 3, no change; 4, a little better; 5, much better.
Out of the total of 32 patients enrolled, 17 patients (53%) were randomized to receive nebulized salbutamol and 15 (47%) to receive Symbicort®. For both treatment arms, by using paired t- and Wilcoxon signed rank tests, it was shown that there were statistically significant improvements in oxygen saturation, PEFR and respiratory rate within the individual treatment groups (pre- vs. post-treatment). Comparing the effects of Symbicort® vs. nebulized salbutamol, the average improvement of oxygen saturation was 1% in both treatment arms (p = 0.464), PEFR 78.67 l/min vs. 89.41 l/min, respectively (p = 0.507), and respiratory rate 2/min vs. 2/min (p = 0.890). For subjective evaluation, all patients reported improvement in the VAS (average 2.45 cm vs. 2.20 cm), respectively (p = 0.765). All patients in both treatment arms reported either "a little better" or "much better" on the 5-point Likert scale, with none reporting "no change" or getting worse.
This study suggests that there is no statistical difference between using Symbicort® vs. nebulized salbutamol as the reliever for the first 15 min post-intervention.
Budesonide/formoterol is an effective treatment for both asthma and chronic obstructive pulmonary disease. This study compared the efficacy and safety of a novel hydrofluoroalkane (HFA) pressurised metered-dose inhaler (pMDI) formulation of budesonide/formoterol with that of budesonide pMDI and budesonide/formoterol dry-powder inhaler (DPI; Turbuhaler®).
This was a 12-week, multinational, randomised, double-blind, double-dummy study involving patients aged ≥ 12 years with asthma. All patients had a forced expiratory volume in 1 s of 50–90% predicted normal and were inadequately controlled on inhaled corticosteroids (500–1600 mu g/day) alone. Following a 2-week run-in, during which they received their usual medication, patients were randomised (two inhalations twice daily) to budesonide pMDI 200 mu g, budesonide/formoterol DPI 160/4.5 mu g or budesonide/formoterol pMDI 160/4.5 mu g. The primary efficacy end-point was change from baseline in morning peak expiratory flow (PEF).
In total, 680 patients were randomised, of whom 668 were included in the primary analysis. Therapeutically equivalent increases in morning PEF were observed with budesonide/formoterol pMDI (29.3 l/min) and budesonide/formoterol DPI (32.0 l/min) (95% confidence interval: −10.4 to 4.9; p = 0.48). The increase in morning PEF with budesonide/formoterol pMDI was significantly higher than with budesonide pMDI (+28.7 l/min; p < 0.001). Similar improvements with budesonide/formoterol pMDI vs. budesonide pMDI were seen for all secondary efficacy end-points. Both combination treatments were similarly well tolerated.
Budesonide/formoterol, administered via the HFA pMDI or DPI, is an effective and well-tolerated treatment for adult and adolescent patients with asthma, with both devices being therapeutically equivalent.
To compare the efficacy and safety of budesonide/formoterol (Symbicort®) with formoterol (Oxis®) in the treatment of patients with acute asthma who showed evidence of refractoriness to short-acting β2-agonist therapy.
In a 3 hour, randomized, double-blind study, a total of 115 patients with acute asthma (mean FEV1 40% of predicted normal) and a refractory response to salbutamol (mean reversibility 2% of predicted normal after inhalation of 400 μg), were randomized to receive either budesonide/formoterol (320/9 μg, 2 inhalations at t = -5 minutes and 2 inhalations at 0 minutes [total dose 1280/36 μg]) or formoterol (9 μg, 2 inhalations at t = -5 minutes and 2 inhalations at 0 minutes [total dose 36 μg]). The primary efficacy variable was the average FEV1 from the first intake of study medication to the measurement at 90 minutes. Secondary endpoints included changes in FEV1 at other timepoints and change in respiratory rate at 180 minutes. Treatment success, treatment failure and patient assessment of the effectiveness of the study medication were also measured.
FEV1 increased after administration of the study medication in both treatment groups. No statistically significant difference between the treatment groups was apparent for the primary outcome variable, or for any of the other efficacy endpoints. There were no statistically significant between-group differences for treatment success, treatment failure or patient assessment of medication effectiveness. Both treatments were well tolerated.
Budesonide/formoterol and formoterol provided similarly rapid relief of acute bronchoconstriction in patients with asthma who showed evidence of refractoriness to a short-acting β2-agonist.
This retrospective, observational cohort study aimed to compare treatment outcomes and healthcare costs in the year after initiation of maintenance treatment with budesonide/formoterol or salmeterol/fluticasone in a German healthcare setting.
Data on German asthma patients initiating treatment with budesonide/formoterol or salmeterol/fluticasone between June 2001 and June 2005 were obtained from the IMS Disease Analyzer database. The primary outcome was the probability of treatment success, defined according to short-acting β2-agonist prescriptions and switches or addition of controller medications, during the postindex year. A secondary definition of treatment success included hospitalisations and oral corticosteroid (OCS) prescriptions. Secondary outcomes included severe asthma exacerbations, defined as ≥1 OCS prescription, asthma-related hospitalisation and/or referral. The effect of treatment on costs was estimated using generalised linear models, adjusting for patient and physician characteristics.
There were no significant differences between the budesonide/formoterol (n=1456) and salmeterol/fluticasone (n=982) groups in disease severity markers in the pre-index year. Patients on budesonide/formoterol had a 44% greater probability of treatment success [odds ratio (OR): 1.44; p = 0.0003] according to the primary definition and a 26% greater probability (OR: 1.26; p = 0.0119) according to the secondary definition, fewer severe exacerbations (−33.4%; p = 0.0123) and fewer OCS prescriptions (−31.5%; p = 0.0082) compared with salmeterol/fluticasone, after controlling for baseline characteristics. Adjusting for covariates, budesonide/formoterol had a significant inverse relationship on asthma-related costs compared with salmeterol/fluticasone (−13.4%; p < 0.001). Total cost (asthma- and non-asthma-related costs) was 12.6% lower for budesonide/formoterol (p < 0.0001).
This study suggests that for patients with chronic asthma in Germany, budesonide/formoterol rather than salmeterol/fluticasone had a higher likelihood of treatment success, and that budesonide/formoterol is the less costly option. Although the cohorts appeared to be well matched at baseline, the results should be interpreted with caution given the observational nature of the study.
Background Previous studies have shown disparities between Black and Hispanic patients compared with other populations in response to asthma medications.
Objective: The aim of this analysis was to assess the effect of budesonide/formoterol pressurized metered-dose inhaler (BUD/FM pMDI) and BUD on predefined criteria for asthma worsening, an asthma control metric generally aligned with definitions of moderate asthma exacerbations, across four different populations.
Methods: Data were from four 12-week, randomized, double-blind,US studies of BUD/FM pMDI treatment in patients aged 12 years or older with varying asthma severities and of varying races. Predefined asthma events and withdrawals due to predefined events were assessed as secondary study endpoints. Study I (NCT00651651) includes data from predominantly White patients with mild to moderate asthma who were randomized to BUD/FM pMDI 160/9 μg twice daily (bid; n = 123) or BUDpMDI 160 μg bid (n = 121). Study II (NCT00652002) includes data from predominantly White patients withmoderate to severe asthma who were randomized to BUD/FM pMDI 320/9 μg bid (n = 124) or BUD pMDI 320 μg bid (n = 109). Study III (NCT00702325) included self-reported Black patients with moderate to severe asthma who were randomized to BUD/FM pMDI 320/9 μg bid (n = 153) or BUD dry powder inhaler 360 μg bid (n = 148). Study IV (NCT00419757) included self-reported Hispanic patients with moderate to severe asthma who were randomized to BUD/FM pMDI 320/9 μg bid (n = 127) or BUD pMDI 320 μg bid (n = 123). Patients were to be withdrawn from the studies if they developed an asthma event, as determined by predefined criteria, except for night-time awakenings, where withdrawal was left to the study physician’s judgment.
Results: Overall, fewer patients in the studies (study I, II, III, and IV, respectively) experienced ≧1 asthma event in the BUD/FM group (18.7%, 29.8%, 37.3%, 25.2%) versus the BUD group (21.5%, 44.0%, 45.3%, 31.7%); only study II results showed a statistically significant difference between treatments. Fewer patients with moderate to severe asthma (studies II, III, and IV) were withdrawn due to ≧1 asthma event in the BUD/FM group (10.5%, 11.8%, 3.1%, respectively) than in the BUD group (20.2%, 18.9%, 6.5%, respectively); however, percentages were similar in the BUD/FM (7.3%) and BUD (6.6%) groups in patients with mild to moderate asthma (study I).
Conclusions: Predefined asthma event rates were numerically or significantly lower for patients with asthma receiving BUD/FMpMDI versusBUD, regardless of race or disease severity. Differences between the BUD/FM pMDI and BUD groupswere smaller in patients with mild to moderate asthma than in those with moderate to severe asthma, most likely because patients with milder disease had lower asthma event rates. Overall, these findings support the efficacy of BUD/FM pMDI in achieving asthma control in patients with moderate to severe asthma.
Improving patients' health-related quality of life (HRQoL) is recognized as a fundamental part of asthma management. The aims of this study were to evaluate the long-term efficacy (including symptom-free days and exacerbations) and impact on HRQoL of a stable-dose regimen of salmeterol/fluticasone propionate (SAL/FP) and an adjustable maintenance dosing (AMD) regimen of formoterol/budesonide (FOR/BUD) where treatment is adjusted based on symptoms [SAM40056].
A total of 688 outpatients with asthma receiving regular low-dose inhaled corticosteroids (ICS) plus a long-acting β2-agonist, or medium dose ICS alone participated in this randomized, double-blind, double-dummy, parallel-group, 1-year trial, which was conducted in 91 centers in 15 countries. Patients were randomized to receive 1 inhalation of SAL/FP 50/250 μg BID or 2 inhalations of FOR/BUD 6/200 μg BID during Weeks 1–4. For Weeks 5–52, patients meeting strict continuation criteria for stable asthma at Week 4 received AMD with FOR/BUD or stable-dose SAL/FP.
The percentage of symptom-free days was significantly greater (58.8% vs 52.1%; p = 0.034) and the annual exacerbation rate was significantly lower (47%; p = 0.008) with stable-dose SAL/FP compared with FOR/BUD AMD. A total of 568 patients completed the Asthma Quality of Life Questionnaire (AQLQ) at least once during the study. The mean change from baseline in AQLQ overall score was numerically greater with SAL/FP than FOR/BUD at week 28 and week 52, but did not reach statistical significance (p = 0.121 at Week 52). However, in a post hoc logistic regression analyses for any AQLQ improvement, significant benefits with SAL/FP were seen at both time points (p = 0.038 and p = 0.009, respectively). The minimally important difference of ≥ 0.5-point improvement in AQLQ overall score was achieved by a significantly greater number of patients receiving SAL/FP at Week 28 (68% vs 60%; p = 0.049); a trend for this difference remained at Week 52 (71% vs 65%) (p = 0.205).
In this population of patients with persistent asthma, stable-dose SAL/FP resulted in significantly greater increases in symptom-free days, a reduction in exacerbation rates, and provided greater HRQoL benefits compared with FOR/BUD AMD.
Clinical Trials registration number NCT00479739
Asthma control is often difficult to measure. The aim of this study was to compare physicians’ personal clinical assessments of asthma control with the Global Initiative for Asthma (GINA) scoring.
Physicians in the adult pulmonary clinics of a tertiary hospital in Oman first documented their subjective judgment of asthma control on 157 consecutive patients. Immediately after that and in the same proforma, they selected the individual components from the GINA asthma control table as applicable to each patient.
The same classification of asthma control was achieved by physicians’ clinical judgment and GINA classification in 106 cases (67.5%). In the other 32.5% (n = 51), the degree of control by clinical judgment was one level higher than the GINA classification. The agreement was higher for the pulmonologists (72%) as compared to non-pulmonologists (47%; P = 0.009). Physicians classified 76 patients (48.4%) as well-controlled by clinical judgment compared to 48 (30.6%) using GINA criteria (P <0.001). Conversely, they classified 34 patients (21.7%) as uncontrolled as compared to 57 (36.3%) by GINA criteria (P <0.001). In the 28 patients who were clinically judged as well-controlled but, by GINA criteria, were only partially controlled, low peak expiratory flow rate (PEFR) (46.7%) and limitation of activity (21.4%) were the most frequent parameters for downgrading the level of control.
Using clinical judgment, physicians overestimated the level of asthma control and underestimated the uncontrolled disease. Since management decisions are based on the perceived level of control, this could potentially lead to under-treatment and therefore sub-optimal asthma control.
Asthma control; Asthma management; Physicians; Treatment; Oman
This study was performed to assess the control asthma and quality of care of asthmatic patient in primary health care facilities in Saint-Petersburg, the second largest city in Russia.
We conducted telephone interviews with 205 asthma outpatients (aged 24 to 90 years). Asthma control was assessed by using the Asthma Control Test (ACT).
During the past 12 month spirometry were performed in 26.8%. Only 2% of outpatients were consulted by allergist and 26.8% - by respiratory physicians. Inhaled corticosteroids were prescribed to persistent asthma patients in 79.1%, oral steroids for maintenance therapy were used in 7.3% of outpatients. Fixed combination of budesonide/formoterol and fluticasone/salmeterol were used in 45.4%. Asthma was uncontrolled for 72.2% of patients.
Quality of diagnostics and treatment of asthma in primary health care is not sufficient and should be improved.
To compare the cost-effectiveness of budesonide-formoterol in a single inhaler used as both maintenance and reliever medication versus clinician-directed titration of salmeterol-fluticasone as maintenance medication, plus salbutamol taken as needed, in controlling asthma in adults and adolescents.
A Canadian economic evaluation was conducted based on the results of a large (n=2143), open-label, randomized, controlled effectiveness trial in which health resource use was prospectively collected. The primary outcome measurement was the time to the first severe exacerbation. Costs included direct medical costs (physician and emergency room visits, hospitalizations, asthma drug costs, etc) and productivity (absenteeism). The time horizon was one year, which corresponded to the duration of the clinical trial. Prices were obtained from 2005 Canadian sources. Both health care and societal perspectives were considered, and deterministic univariate sensitivity analyses were conducted.
In the clinical trial, budesonide-formoterol as maintenance and reliever treatment was superior to salmeterol-fluticasone with respect to the time to the first severe exacerbation, overall rate of exacerbations and use of as-needed reliever medication. The annualized rate of severe exacerbations was 0.24 events/patient in the budesonide-formoterol arm and 0.31 events/patient in the salmeterol-fluticasone arm (P=0.0025). From a health care perspective, the mean cost per patient-year was $1,315 in the budesonide-formoterol arm versus $1,541 in the salmeterol-fluticasone arm. From a societal perspective, the mean cost per patient-year was $1,538 in the budesonide-formoterol arm and $1,854 in the salmeterol-fluticasone arm. Budesonide-formoterol was dominant (more effective and less expensive) in the base case analysis from both perspectives. The results were robust under sensitivity testing.
The strategy that allows budesonide-formoterol to be used in a single inhaler as both maintenance and reliever medication proved to be more effective and less expensive than a strategy of clinician-directed titration of salmeterol-fluticasone with salbutamol as reliever therapy.
Asthma; Budesonide-formoterol; Comparison; Economic evaluation; Salmeterol-fluticasone
The budesonide–formoterol dry powder inhaler (Symbicort® Turbuhaler® 160/4.5–640/18 μg/day) contains the long-acting β2-adrenoreceptor agonist formoterol and the inhaled corticosteroid budesonide. Two large, 12-month trials examined the effect of budesonide–formoterol 160/4.5 μg twice daily in COPD patients who met these criteria. The studies were identical, except one in which the patients had received oral prednisolone 30 mg/day and had inhaled formoterol 4.5 μg twice daily for 2 weeks before randomization. In terms of the FEV1, budesonide–formoterol produced an effect greater than that of both budesonide alone and formoterol alone reported in previous studies. The combination was generally more effective than either of the components in terms of peak expiratory flow, symptoms, and exacerbations. These advantages of the combination over those of either budesonide alone or formoterol alone were quite consistent. Improving lung function and decreasing symptoms significantly, budesonide–formoterol combination therapy provides significant clinical improvements in COPD, despite the limited reversibility of impaired lung function in the disease.
chronic obstructive lung disease; budesonide–formoterol; budesonide; formoterol; combination therapy; dry powder inhalation
A reduced response to inhaled corticosteroids (ICS) has been reported in smoking asthmatic patients but the effects of other medications remain to be evaluated in this population.
Subjects and Methods:
We evaluated the effects of a combined therapy of budesonide 200 µg twice daily and formoterol 6 µg twice daily compared with budesonide 200 µg twice daily alone on asthma control questionnaire (ACQ), asthma quality of life questionnaire (AQLQ- Juniper), pulmonary function and airway inflammation, in a cross-over randomized double-blind study with treatment periods of two months separated by a one-month wash-out period. Seventeen smoking and 22 non-smoking patients not using inhaled corticosteroids with slightly uncontrolled mild asthma completed the study.
ACQ and AQLQ scores were similar in both groups at baseline and improved similarly after treatments. β2-agonist use was higher in smokers, regardless of the treatment received (p=0.03), as it was on baseline (p=0.003). Smokers treated with budesonide/formoterol showed an increase in the number of asthma episodes (intercurrent asthma symptoms, p=0.016) while non-smoking subjects had a significant decrease in these episodes (p=0.009). No difference was found between smokers and non-smokers in regard to post-treatment airway inflammatory parameters.
No significant differences were found between smoking and non-smoking subjects with mild asthma in regard to clinical changes in asthma control, pulmonary function and airway inflammation following a 2-month treatment period with budesonide or the association of budesonide and formoterol for a period of 2 months. This should be further explored in larger groups of subjects.
Asthma; formoterol; budesonide; smoking.
A 48-year-old female patient with uncontrolled severe asthma was referred to our hospital for anti-IgE therapy. She was suffering with persistent wheezing and dyspnea after a severe asthma attack that had taken place 5 months previously. Her asthma had not been controlled with adequate asthma treatment, including budesonide at 320 μg + formoterol at 9 μg b.i.d. combination, montelukast at 10 mg/day, and oral steroids (30–40 mg/day of prednisolone), during this period. She was hospitalized for evaluation for anti-IgE therapy. Chest radiography revealed a left-sided hilar opacity. Fiberoptic bronchoscopy was performed and showed an endobronchial lesion obstructing the left lower bronchus lumen. Computed tomography also revealed a nodular lesion at the same location. The patient underwent left lower lobectomy and mediastinal lymph node dissection. Pathological examination concluded the diagnosis of typical carcinoid tumor. After surgery, her symptoms disappeared and she has had no recurrence. In conclusion, a diagnosis of severe asthma requires confirmation of asthma. Uncontrolled symptoms that linger despite aggressive therapy warrant evaluation to rule out other etiologies, such as a carcinoid tumor, before selecting new treatment options.
Asthma; carcinoid tumor; intrabronchial tumor; pulmonary carcinoids; severe allergic asthma; typical carcinoid tumor; uncontrolled asthma
Combination therapy with budesonide and formoterol reduces exacerbations of asthma, which are closely associated with human rhinovirus (RV) infections in both children and adults. These data suggest that budesonide and formoterol inhibit virus-induced inflammatory responses of airway epithelial cells.
To test this hypothesis, bronchial epithelial (BE) cells were obtained from airway brushings of 8 subjects with moderate-to-severe allergic asthma and 9 with neither asthma nor respiratory allergies. Cultured BE cells were incubated for 24 hours with budesonide (1.77 μM), formoterol (0.1 μM), both, or neither, and then inoculated with RV-16 (5×106 plaque forming units [PFU]/mL). After 24 hours, viral replication (RV RNA), cytokine secretion (CXCL8, CXCL10, TNFα, IFN-β, IL-28) and mRNA expression (CXCL8, CXCL10, TNF, IFNB1, IL28A&B) were analyzed.
RV infection induced CXCL10 protein secretion and IFNB1 and IL28 mRNA expression. Drug treatments significantly inhibited secretion of CXCL10 in mock-infected, but not RV-infected, BE cells, and inhibited secretion of TNFα under both conditions. Neither budesonide nor formoterol, alone or in combination, significantly affected viral replication, nor did they inhibit RV-induced upregulation of IFNB1 and IL28 mRNA. Overall, RV replication was positively related to CXCL10 secretion and induction of IFNB1 and IL28 mRNA, but the positive relationship between RV RNA and CXCL10 secretion was stronger in normal subjects than in subjects with asthma.
Budesonide and formoterol can inhibit BE cell inflammatory responses in vitro without interfering with viral replication or production of interferons. These effects could potentially contribute to beneficial effects of budesonide/formoterol combination therapy in preventing RV-induced asthma exacerbations.
Budesonide; Formoterol; Human rhinovirus; Bronchial epithelial cells; Asthma