Randomised, placebo controlled trial of effect of a leukotriene receptor antagonist, montelukast, on tapering inhaled corticosteroids in asthmatic patients. Effects of pranlukast, a cysteinyl leukotriene receptor 1 antagonist, combined with inhaled beclomethasone in patients with moderate or severe asthma. Zafirlukast versus budesonide on bronchial reactivity in subjects with mild-persistent asthma. Effectiveness of montelukast versus budesonide on quality of life and bronchial reactivity in subjects with mild-persistent asthma. [Pranlukast allows reduction of inhaled steroid dose without deterioration in lung function in adult asthmatics]. Leukotriene antagonist prevents exacerbation of asthma during reduction of high-dose inhaled corticosteroid. The Tokyo Joshi-Idai Asthma Research Group. Randomised controlled trial of montelukast plus inhaled budesonide versus double dose inhaled budesonide in adult patients with asthma. Zafirlukast improves asthma control in patients receiving high-dose inhaled corticosteroids. Effect of montelukast added to inhaled budesonide on control of mild to moderate asthma. Dose reduction of inhaled corticosteroids under concomitant medication with montelukast in patients with asthma. Leukotriene receptor antagonist, montelukast, can reduce the need for inhaled steroid while maintaining the clinical stability of asthmatic patients. Montelukast added to inhaled beclomethasone in treatment of asthma. Montelukast/Beclomethasone Additivity Group. Effect of the addition of montelukast to inhaled fluticasone propionate on airway inflammation.
To determine the ability of montelukast, a leukotriene receptor antagonist, to allow tapering of inhaled corticosteroids in clinically stable asthmatic patients.
                Double blind, randomised, placebo controlled, parallel group study. After a single blind placebo run in period, during which (at most) two inhaled corticosteroids dose decreases occurred, qualifying, clinically stable patients were allocated randomly to receive montelukast (10 mg tablet) or matching placebo once daily at bedtime for up to 12 weeks.
                23 academic asthma centres in United States, Canada, and Europe.
                226 clinically stable patients with chronic asthma receiving high doses of inhaled corticosteroids (113 randomised to montelukast and 113 to placebo).
                Every 2 weeks, the inhaled corticosteroids dose was tapered, maintained, or increased (rescue) based on a standardised clinical score.
                Last tolerated dose of inhaled corticosteroids.
                Compared with placebo, montelukast allowed significant (P=0. 046) reduction in the inhaled corticosteroid dose (montelukast 47% v placebo 30%; least square mean difference 17.6%, 95% confidence interval 0.3 to 34.8). Fewer patients on montelukast (18 (16%) v 34 (30%) placebo, P=0.01) required discontinuation because of failed rescue.
                Montelukast reduces the need for inhaled corticosteroids among patients requiring moderate to high doses of corticosteroid to maintain asthma control. Although inhaled steroids are used as the first line of therapy in asthmatic patients, symptoms of asthma do not improve completely in some patients.
                To investigate the effects of pranlukast, a cysteinyl leukotriene receptor 1 antagonist, in patients with moderate/severe asthma, when combined with beclomethasone dipropionate (BDP).
                Protocol 1: After a 2-week observation period, 41 patients with moderate asthma were divided into those receiving BDP at 1,600 microg/day or 800 microg/day + pranlukast (450 mg/day). The effect of treatment was evaluated by measuring AM peak expiratory flow rate, symptom score, frequency of beta2-agonists, and daily variability of peak expiratory flow rate. Protocol 2: 39 patients participated in this study including those with moderate asthma on 800 microg/day BDP (group I), severe asthma on BDP at 1,600 microg/day (group II), and severe asthma on 1,600 microg/day BDP + 5 to 20 mg prednisolone (group III). Patients of all groups were additionally treated with pranlukast.
                Protocol 1: Both treatment regimens resulted in improvement in each clinical parameter. There were no significant differences in the effects of two treatment regimens. Protocol 2: Pranlukast was effective in group I and II, but not in group III. In groups I and II, pranlukast tended to be more effective when BDP was introduced within the first year of onset of asthma.
                Pranlukast is effective for patients with moderate asthma and those patients with severe asthma who are not treated with oral steroids. Pranlukast is more effective in patients treated with BDP early after onset. Asthma is one of the most common chronic diseases in children and adults. Recent studies have shown that in asthmatic patients treated with inhaled corticosteroids there is a better diseases control when adding a second drug, than increasing the corticosteroids dose. The aim of this study has been to evaluate the effectiveness and tolerance of zafirlukast, a leukotriene receptor antagonist, versus budesonide in clinically steady patients with mild persistent bronchial asthma. We have enrolled 36 subjects non smokers, with mild persistent bronchial asthma and 12 healthy subjects as control group. At the beginning of this study and at the end of the treatment (8 weeks), all patients underwent complete clinical work-up, pulmonary function testing (FEV1, PEF and FVC) and methacholine challenge test. The patients were divided into 3 groups: group A) 20 mg of zafirlukast twice a day; group B) 400 mg of budesonide twice a day; group C) 20 mg of zafirlukast twice a day and 400 mg of budesonide twice a day. Basal FEV1 and PEF presented no significant statistical differences between control subjects and patients of group A, B and C. After eight weeks there were no significant changes for FEV1 and PEF among the three groups. After therapy a strong significant increase of PD20 was documented in group A (p&#x003C;0.005), group B (p&#x003C;0.001) and group C (p&#x003C;0.005), respect to baseline values. The antileukotriene drugs could be taken as an alternative drug, or in association with low-dose inhaled corticosteroids, in patients with mild persistent asthma, both for their clinical effectiveness and their easy ingestion, which is confirmed in compliance studies on inhaled steroids. Insufficient data exist to evaluate the comparative effects of inhaled corticosteroids (ICS) versus leukotriene receptor antagonist (LTRA) on airway inflammation and quality of life (QoL). The aim of the study was to compare the effectiveness of montelukast compared to budesonide at different doses on QoL and bronchial reactivity in mild-asthmatic adult patients. 45 subjects with bronchial asthma were randomly assigned to a different treatment and divided in 3 treatment groups: A: 400 mg of budesonide twice a day; B: 10 mg of montelukast daily; C: 10 mg of montelukast daily plus 400 mg of budesonide twice a day. At the beginning of the study and at the end of the treatment period (16 weeks) all patients underwent complete clinical evaluation, pulmonary function testing and methacholine challenge test (MCHt). In group A the increase from baseline was 153.4&amp;#x0025;, in group C was 133.2&amp;#x0025;, and in group B 247.7&amp;#x0025;, the latter increase being statistically significant compared to that in the other 2 groups (p&amp;#x003C; 0.005 Wilcoxon test). In all domains the improvement in quality of life in the group treated with montelukast (group B) was significantly greater than that in the group treated with both medications (group C): in particular, the improvement was consistent in the symptoms (p&amp;#x003C; 0.01) and emotions (p&amp;#x003C; 0.01) domains, and weaker in the physical activity (p&amp;#x003C; 0.05). A similar difference was observed between group B and A, but only in the symptoms (p&amp;#x003C;0.01), emotions (p&amp;#x003C;0.01), and environmental stimuli domains (p&amp;#x003C;0.05). The personal perception of their own disease is important for a correct therapeutic management of asthma. In order to optimize the treatment, a complete adherence of the patient to the treatment itself is required, to be achieved through simplification of therapeutic schedule and easy administration of medications. Montelukast may be considered a valid alternative in the treatment of mild-persistent asthma, both for the clinical and functional benefits and for the great advantage of the once-daily dosage, which consistently improves the compliance with the chronic treatment of the disease. We undertook a community based case-control study to measure the effect of pranlukast on the reduction of inhaled steroid in adult asthmatics. Forty-one adults completed a run-in period of 4 weeks on 800 microgram of beclomethasone dipropionate (BDP) documenting twice daily peak expiratory flow (PEF) and symptom score and therapeutic score on a standard diary. Forced expiratory volume in one second (FEV1.0), V50, V25 was measured once during the run-in period. Patients were then randomized to receive either pranlukast with 400 microgram of BDP or 400 microgram alone for 8 weeks. There was no difference in the symptom score and therapeutic between the two groups at any time point. However, morning and evening % PEF run-in expressed as a % of the PEF average during the run-in period was significantly lower at 8 weeks in the groups without pranlukast. There were subjects in the group without pranlukast (35.3%) compared to those with (20.8%) who had a 10% or more reduction in % PEF from the run-in period. The patients with an FEV1.0 < 80% predicted who were randomized to the control group were more likely (5 of 7) to have a fall in % PEF run-in and those randomized to received pranlukast were less likely to have a fall in % PEF run-in though this was not significant (2 of 6). In this study, pranlukast has demonstrated steroid sparing effect. Severe asthmatics (FEV1.0 < 80%) who deteriorate after reduction of inhaled steroid may benefit most from pranlukast. Larger studies are now required to explore this important effect. To test whether the leukotriene antagonist ONO-1078 (pranlukast) prevents asthma exacerbations during reduction of high-dose inhaled corticosteroid, we conducted a randomized, double-blind, placebo-controlled study in 79 asthma patients requiring high doses (1,500 microg/d or more) of inhaled beclomethasone dipropionate (BDI) for clinical control (duration of asthma, 11.0 +/- 3.1 yr; duration of BDI treatment, 0.5 +/- 0.3 yr; FEV1 percentage of predicted, 80.7 +/- 2.0%). After a 2-wk run-in period, the doses of BDI were halved, while the patients were assigned to receive orally ONO-1078, 450 mg twice daily, or placebo. In the placebo group FEV1 decreased by 0.33 +/- 0.20 L after 6 wk (p < 0.001). Likewise, morning and evening PEF decreased by 46 +/- 7 L/min and 18 +/- 6 L/min, respectively. By contrast these variables were sustained above baseline in the ONO-1078 group. The number of daytime and nighttime asthma symptoms and the use of beta2-agonist increased in the placebo group, whereas they remained unchanged in the ONO-1078 group. In the placebo group concentrations of serum eosinophil cationic protein and exhaled nitric oxide increased (p = 0.007 and p = 0.025, respectively), compared with no change in the ONO-1078 group. Therefore, the leukotriene antagonist ONO-1078 prevents the asthma deterioration provoked by a 6-wk reduction of the dose of inhaled BDI into half. Inhaled corticosteroids (ICS) affect many inflammatory pathways in asthma but have little impact on cysteinyl leukotrienes. This may partly explain persistent airway inflammation during chronic ICS treatment and failure to achieve adequate asthma control in some patients. This double blind, randomised, parallel group, non-inferiority, multicentre 16 week study compared the clinical benefits of adding montelukast to budesonide with doubling the budesonide dose in adults with asthma.
                After a 1 month single blind run in period, patients inadequately controlled on inhaled budesonide (800 microg/day) were randomised to receive montelukast 10 mg + inhaled budesonide 800 microg/day (n=448) or budesonide 1600 microg/day (n=441) for 12 weeks.
                Both groups showed progressive improvement in several measures of asthma control compared with baseline. Mean morning peak expiratory flow (AM PEF) improved similarly in the last 10 weeks of treatment compared with baseline in both the montelukast + budesonide group and in the double dose budesonide group (33.5 v 30.1 l/min). During days 1-3 after start of treatment, the change in AM PEF from baseline was significantly greater in the montelukast + budesonide group than in the double dose budesonide group (20.1 v 9.6 l/min, p<0.001), indicating faster onset of action in the montelukast group. Both groups showed similar improvements with respect to "as needed" beta agonist use, mean daytime symptom score, nocturnal awakenings, exacerbations, asthma free days, peripheral eosinophil counts, and asthma specific quality of life. Both montelukast + budesonide and double dose budesonide were generally well tolerated.
                The addition of montelukast to inhaled budesonide is an effective and well tolerated alternative to doubling the dose of inhaled budesonide in adult asthma patients experiencing symptoms and inadequate control on budesonide alone. Not all asthma can be adequately controlled, despite the use of high-dose inhaled corticosteroids. Because cysteinyl-leukotrienes (Cys-LT) have been implicated in the pathogenesis of asthma, we hypothesized that the leukotriene receptor antagonist zafirlukast, in combination with high-doses of inhaled corticosteroids, might be efficacious in severe asthma. In a double-blind, parallel group study, 368 chronic adult asthmatic patients treated with inhaled corticosteroids (1,000 to 4,000 microgram/d), who had a predefined level of asthma symptoms during the run in period of the study, were randomly assigned to receive additional treatment with a high dose of zafirlukast (80 mg twice daily) (n = 180) or placebo (n = 188) for 6 wk. Compared with placebo, zafirlukast produced a significant improvement over baseline in the primary study endpoint of mean morning peak expiratory flow rate (PEFR) (18.7 L/min versus 1.5 L/min, p < 0.001), as well as in evening PEFR (p < 0.01), FEV(1) (p < 0.05), daytime symptom score (p < 0.001), and beta(2)-agonist use (p < 0.001). Furthermore, zafirlukast significantly reduced the risk of an exacerbation of asthma (odds ratio [OR]: 0.61; 95% confidence interval [CI]: 0.38 to 0.99) and the risk of patients requiring a further increase in asthma controller therapy (OR: 0.4; 95% CI: 0.2 to 0.8). In conclusion, in patients taking high-dose inhaled corticosteroids, zafirlukast improves pulmonary function and asthma symptoms, and reduces the risk of an asthma exacerbation, suggesting that the contribution of leukotrienes to asthma symptoms and exacerbations is not adequately controlled by high-dose inhaled corticosteroids. Proinflammatory leukotrienes, which are not completely inhibited by inhaled corticosteroids, may contribute to asthmatic problems [corrected]. A 16 week multicentre, randomised, double blind, controlled study was undertaken to study the efficacy of adding oral montelukast, a leukotriene receptor antagonist, to a constant dose of inhaled budesonide.
                A total of 639 patients aged 18-70 years with forced expiratory volume in 1 second (FEV(1)) > or =55% predicted and a minimum predefined level of asthma symptoms during a 2 week placebo run in period were randomised to receive montelukast 10 mg (n=326) or placebo (n=313) once daily for 16 weeks. All patients received a constant dose of budesonide (400-1600 microg/day) by Turbuhaler throughout the study.
                Mean FEV(1) at baseline was 81% predicted. The median percentage of asthma exacerbation days was 35% lower (3.1% v 4.8%; p=0.03) and the median percentage of asthma free days was 56% higher (66.1% v 42.3%; p=0.001) in the montelukast group than in the placebo group. Patients receiving concomitant treatment with montelukast had significantly (p<0.05) fewer nocturnal awakenings and significantly (p<0.05) greater improvements in beta agonist use and morning peak expiratory flow rate (PEFR).
                For patients with mild airway obstruction and persistent asthma symptoms despite budesonide treatment, concomitant treatment with montelukast significantly improves asthma control. The present study aimed at comparing the effects of a dose reduction of inhaled corticosteroids on lung function, indirect measures of airway inflammation and clinical scores during treatment with a leucotriene receptor antagonist. In 50 patients (mean forced expiratory volume in one second (FEV1) 94% predicted), steroid doses (800 microg beclomethasone dipropionate) were first reduced to 50% and then to 25%, for 6 weeks each. One group received a placebo and the other group received montelukast (10 mg). The first reduction did not cause significant effects. During the second, FEV1 and peak expiratory flow decreased in both groups (p<0.001). Daytime symptoms were not altered with placebo but were reduced by montelukast (p<0.05). Night-time symptoms were slightly elevated with placebo (p<0.05) but not montelukast, as well as the use of supplemental salbutamol. Changes in provocative concentration of methacholine causing a 20% fall in FEV1 (PC20), sputum eosinophils and exhaled nitric oxide were mostly nonsignificant for both placebo and montelukast. These data demonstrate that a 75% reduction in the dose of steroid given to patients with asthma led to a deterioration in lung function not prevented by montelukast, whereas changes in clinical state seemed to favour montelukast treatment. It therefore appears that potential effects of montelukast, in the presence of low-dose steroids, could not be attributed to single indices of lung function or airway inflammation. Oral leukotriene receptor antagonists have been shown to have efficacy in chronic asthma.
                To determine whether the addition of montelukast could lead to a reduction in inhaled corticosteroid dose without a significant decrease in peak expiratory flow rate (PEFR).
                After a 4-week run-in period, 191 moderate-to-severe asthmatic patients whose asthma had been well controlled with daily inhaled corticosteroid therapy (beclometasone dipropionate 800 to 1600 micro g/day), were randomly assigned to one of two treatments - placebo (n = 98) or montelukast 10 mg once daily (n = 93) - for a 24-week, multicentre, double-blind, treatment period. At the beginning of the active treatment period, the daily dose of inhaled corticosteroid was halved in all of the patients. In addition, the inhaled corticosteroid dose was subsequently titrated every 8 weeks, based on PEFR, asthma symptoms and beta-agonist use.
                After 8 weeks of a 50% reduction in inhaled corticosteroid use, morning PEFR increased by 5.3 +/- 32.3 L/min from baseline in patients receiving montelukast and significantly decreased by 6.9 +/- 29.0 L/min in those receiving placebo (P = 0.035). In addition, evening PEFR significantly decreased by 9.8 +/- 28.5 L/min (P = 0.003) in the placebo group, but was maintained in the montelukast group. In spite of a subsequent 50% reduction in the inhaled corticosteroid dose every 8 weeks, morning and evening PEFRs were maintained over the 24-week treatment period in the montelukast group; PEFR significantly decreased in the placebo group. There was a significant difference between the two groups with regard to morning PEFR, therapy score and asthmatic score at weeks 8, 16 and 24, as well as evening PEFR at week 8. However, the symptom scores were not significantly different between the two groups or within each group.
                These data suggest that montelukast reduces the need for inhaled corticosteroids while maintaining asthma control over a 24-week period. Therefore, montelukast may be useful for long-term treatment in patients with asthma who require high doses of inhaled corticosteroids. The primary objective of this study was to determine whether montelukast, an oral leukotriene receptor antagonist, provides additional clinical benefit to the effect of inhaled corticosteroids. A total of 642 patients with chronic asthma (FEV(1) 50 to 85% of predicted value and at least a predefined level of asthma symptoms) incompletely controlled with inhaled beclomethasone, 200 microg twice daily using a spacer device, during the 4-wk run-in period were randomly allocated, in a double-blind, double-dummy manner to one of four treatment groups: (1) montelukast 10 mg plus continuing inhaled beclomethasone; (2) placebo tablet plus continuing inhaled beclomethasone; (3) montelukast 10 mg and inhaled placebo (after blind beclomethasone removal); and (4) placebo tablet and inhaled placebo (after blind beclomethasone removal). The primary endpoints were FEV(1) and daytime asthma symptoms score. Montelukast provided significant (p < 0.05) clinical benefit in addition to inhaled beclomethasone by improving FEV(1), daytime asthma symptom scores, and nocturnal awakenings. Blind removal of beclomethasone in the presence of placebo tablets caused worsening of asthma control, demonstrating that patients received clinical benefit from inhaled corticosteroids. Blind removal of beclomethasone in the presence of montelukast resulted in less asthma control but not to the level of the placebo group. All treatments were well tolerated; clinical and laboratory adverse experiences were generally similar to placebo treatment in this study. In conclusion, montelukast provided additional asthma control to patients benefitting from, but incompletely controlled on, inhaled beclomethasone. The aim of the study was to investigate the effect of addition of montelukast to inhaled fluticasone propionate (FP) therapy, compared with FP therapy alone (100 microg twice a day) on airway immunopathology in individuals with mild asthma. Twenty-eight subjects received FP (100 microg twice a day) or FP (100 microg twice a day) plus montelukast (10 mg at night) for 8 weeks and were then crossed over to the alternate treatment for a further 8 weeks. Physiological measurements and bronchial biopsies were obtained at +/- 2 days before treatment and +/- 2 days at the end of each treatment period. A two-period crossover analysis was performed and the mean and SE were calculated. There was no significant difference in percent predicted FEV1 (p = 0.51) or PC20 mg/ml (p = 0.81) between the two treatment regimes after 8 weeks of therapy. There was no difference in the efficacy of either treatment in decreasing T cell (p = 0.97), CD45RO+ (p = 0.37), mast cell (p = 0.37), or activated eosinophils (p = 0.55) numbers in bronchial biopsies. There was no significant difference in the percentage area stained for IFN-gamma (p = 0.76) or interleukin-4 (p = 0.61) between treatments. Reduction of inflammatory cell numbers in the bronchial mucosa achieved with FP plus montelukast was not significantly different from the reduction observed with FP alone in individuals with mild asthma.
The addition of licensed doses of anti-leukotrienes to add-on therapy to inhaled glucocorticoids brings modest improvement in lung function. Although addition of anti-leukotrienes to inhaled glucocorticoids appears comparable to increasing the dose of inhaled steroids, the power of the review is insufficient to confirm the equivalence of both treatment options. Addition of anti-leukotrienes is associated with superior asthma control after glucocorticoid tapering; although the glucocorticoid-sparing effect cannot be quantified at present, it appears modest.