Percentage Of Rescue-free Days Research Articles

The Efficacy and Safety of Fluticasone/Salmeterol Compared to Fluticasone in Children Younger Than Four Years of Age

The combination of inhaled corticosteroid (ICS) and long-acting β-2 agonist (LABA) is widely used as maintenance therapy for children with asthma. However, use in young children has not been well studied. This study investigates the efficacy and safety of combination therapy with fluticasone propionate 50 µg and salmeterol xinafoate 25 µg in children up to 4 years of age.Study participants were children aged 6 months to 4 years with asthma diagnosed according to the Japanese Pediatric Guideline for the Treatment and Management of Asthma 2012 and in whom ICS and LABA was considered necessary by their physician.This 27-week double-blind, randomized controlled trial was conducted from May 2014 to October 2016 in 70 Japanese pediatric centers. The study consisted of 4 time intervals: (1) a 2-week run-in period, during which all children received inhaled fluticasone propionate twice daily; (2) an 8-week randomized treatment period, during which fluticasone only or fluticasone and salmeterol was administered twice daily; (3) a 16-week open-label period, during which all children received fluticasone and salmeterol twice daily; and (4) a 1-week follow-up period, during which children received care that the investigator felt was appropriate. Children <2 years received 1 inhalation per dose, whereas children 2 years or older received 1 to 2 inhalations per dose, according to the investigator’s judgment. The number of inhalations remained consistent during the run-in and treatment phases but could be adjusted during the open-label phase, if appropriate. As needed, salbutamol 100 µg was allowed as a rescue inhaler. Study endpoints and compliance were assessed via twice-daily recordings in a patient diary by the parent or legal guardian.A total of 300 patients were randomized 1:1 to the double-blind period, of whom 148 completed treatment with ICS and LABA, and 142 completed treatment with ICS only. The study was completed by 268 patients. In both treatment groups, boys predominated, and the majority (≥90%) of patients had moderate or severe persistent asthma. Both groups showed reduction in total asthma symptom scores; however, the primary end point of mean change in total asthma symptom scores from baseline to the last 7 days of the treatment period was not significantly different between the 2 groups (−3.97 for ICS and LABA versus −3.01 for ICS only, P = .21). Secondary outcome analysis showed fewer exacerbations in the ICS and LABA group (3% vs 5% in the ICS group) and statistically greater mean change from baseline in Japanese Pediatric Asthma Control scores in the ICS and LABA group (0.4 points vs −0.3 points for ICS only, P = .04). Little change from baseline in daily rescue medication use or percentage of rescue-free days was seen, with no statistically significant differences between the groups. Incidence of adverse effects was virtually identical between the ICS and LABA (74%) and ICS only (73%) groups and was not associated with age or number of inhalations. No new safety concerns were identified during the open-label period. Decreased plasma cortisol was reported in 6 children during the open-label and follow-up periods, although most values normalized on recheck. No serious adverse effects were considered by the investigators to be drug related.Combination therapy with ICS and LABA showed similar safety profiles to ICS alone in children with asthma up to 4 years of age. Although combination therapy improved total asthma symptom scores, it did not show superior efficacy to ICS alone.Asthma management in young children is challenging because of inability to perform pulmonary function tests and the intermittent nature of symptoms, with many children being clinically well in between exacerbations. Importantly, this study provides new evidence regarding the safety of ICS and LABA use in young children. Regarding efficacy, statistically significant differences were seen for some secondary outcomes, which may suggest better symptom control with ICS and LABA, although it is unclear if these differences warrant the use of ICA and LABA over ICS only in this age group. Further studies are needed to make this determination and support the findings in this study.

A Phase 2a Study of DP2 Antagonist GB001 for Asthma

GB001, a DP2 antagonist, may inhibit recruitment and activation of inflammatory cells in patients with asthma, consequently reducing airway inflammation. Explore the efficacy and safety of GB001 in adults with mild to moderate asthma. During a 4-week run-in period, adult patients with asthma (N= 158) received medium-dose inhaled corticosteroid and placebo and were then randomized to treatment once daily with GB001 5 mg, 20 mg, or placebo for 16 weeks or until asthma worsening/exacerbation. Patients were tapered to and then discontinued from low-dose inhaled corticosteroid at randomization and at 4 weeks postrandomization, respectively. Primary end point was change in morning peak expiratory flow (AM PEF); secondary end points included measures of asthma control. Safety was also assessed. Baseline characteristics were similar among GB001 5 mg, 20 mg, and placebo groups. Changes in AM PEF in 5 mg and 20 mg groups versus placebo showed mean differences (95% CI) of 15.2 (3.1-27.4) L/min (P= .02) and 13.7 (1.5-25.8) L/min (P= .03), respectively. The changes in forced expiratory volume in 1 second of 55 mL and 32 mL, respectively, were not significant. There was a significant difference between GB001 20 mg and placebo for the secondary end points of time to asthma worsening/exacerbation (hazard ratio, 0.29), 5-item Asthma Control Questionnaire score (-0.60 point), the percentage of days without asthma symptoms (26%), and the percentage of rescue-free days (22%). Patients with baseline eosinophil levels greater than or equal to 300/μL had larger differences between GB001 20 mg and placebo for changes in AM PEF. Similar effects were seen in a post hoc analysis for time to worsening/exacerbations and 5-item Asthma Control Questionnaire score. The most common nonserious adverse event in the GB001 groups compared with the placebo group was nasopharyngitis. GB001 was well tolerated and although not associated with clinically meaningful changes in lung function, improvements in asthma worsening/exacerbations and markers of asthma control were demonstrated. In addition, greater treatment effects were observed in patients with high baseline blood eosinophils. Further studies are needed to confirm these findings in the context of standard of care treatment.

Once-daily long-acting beta₂-agonists/inhaled corticosteroids combined inhalers versus inhaled long-acting muscarinic antagonists for people with chronic obstructive pulmonary disease.

Three classes of inhaler medication are used to manage chronic obstructive pulmonary disease (COPD): long-acting beta₂-agonists (LABA); long-acting muscarinic antagonists (LAMA); and inhaled corticosteroids (ICS). To encourage patient adherence, two classes of medication are often combined in a single medication device; it seems that once-daily dosing offers greatest convenience to patients and may markedly influence adherence. To compare a once-daily combination of inhaled corticosteroid and long-acting beta₂-agonist inhalers (ICS/LABA) versus inhaled long-acting muscarinic antagonists alone (LAMA) for people with chronic obstructive pulmonary disease (COPD). We performed an electronic search of the Specialised Register of the Cochrane Airways Group (14 May 2018), ClinicalTrials.gov (14 May 2018), and the World Health Organization International Clinical Trials Registry Platform (20 September 2017), then a search of other resources, including reference lists of included studies and manufacturers' trial registers (10 October 2017). Two pairs of review authors screened and scrutinised selected articles. We included randomised controlled trials (RCTs) comparing once-daily administered ICS/LABA and LAMA in adults with COPD. Two review authors independently extracted data and assessed risk of bias in each study. We analysed dichotomous data as random-effects odds ratios (ORs) and continuous data as mean differences (MDs), both with 95% confidence intervals (95% CIs), using Review Manager 5. We included two studies with 880 participants. We identified one ongoing trial with planned recruitment of 80 participants. Included studies enrolled participants with both partially reversible and non-reversible COPD and baseline mean per cent predicted (%pred) forced expiratory volume in one second (FEV₁) of 43.4 to 49.6. Both studies lasted 12 weeks. Both studies used the same combination of inhaled ICS/LABA (fluticasone furoate and vilanterol 100/25 mcg once daily; FF/VI) versus LAMA (18 mcg tiotropium; TIO). They were published as full articles, and neither study was at low risk of bias in all domains.Compared to the TIO arm, results for pooled primary outcomes for the FF/VI arm were as follows: mortality: OR 0.20, 95% CI 0.02 to 1.73, 880 participants (deaths reported only in the TIO arm), very low-quality evidence; COPD exacerbation (requiring short-burst oral corticosteroids or antibiotics, or both): OR 0.72, 95% Cl 0.35 to 1.50, 880 participants, very low-quality evidence; pneumonia: reported in both studies only during treatment with FF/VI: OR 6.12, 95% Cl 0.73 to 51.24, 880 participants, very low-quality evidence; and total serious adverse events: OR 0.96, 95% Cl 0.50 to 1.83, 880 participants, very low-quality evidence. None of the pneumonias were fatal. Compared to the TIO arm, we found no statistically significant difference for pooled secondary outcomes, including St George's Respiratory Questionnaire (SGRQ) mean total score change; hospital admissions (all-cause); disease-specific adverse events; mean weekly rescue medication use (results available from only one of the studies); and mean weekly percentage of rescue-free days for FF/VI. We found no statistically significant differences between ICS/LABA and LAMA for improvement in symptoms measured by the COPD Assessment Test (CAT score) nor for FEV₁ (change from baseline trough in 24-hour weighted mean on treatment day 84). Many pooled estimates lacked precision. Data for other endpoints such as exacerbations leading to intubation and physical activity measures were not available in included trials. Based on analysis of primary and secondary outcomes, we are uncertain whether once-daily ICS/LABA, combined in one inhaler, has a different efficacy or adverse effect profile compared to LAMA for treatment of people with COPD. However, the current review is based on only two trials with the main focus on primary outcomes other than those considered in this review. The short follow-up period and the very low quality of evidence limit our confidence in the result and increase uncertainty. Further trials of longer duration are needed. Current evidence is not strong enough to demonstrate important differences between inhalers in terms of effects, nor to establish that once-daily fluticasone/vilanterol 100/25 mcg and tiotropium 18 mcg are equivalent.

Once daily Long-acting beta2 -agonists/Inhaled corticosteroids combined inhalers versus inhaled long-acting muscarinic antagonists for people with chronic obstructive pulmonary disease

Background Three classes of inhaler medication are used to manage chronic obstructive pulmonary disease (COPD): long-acting beta₂-agonists (LABA); long-acting muscarinic antagonists (LAMA); and inhaled corticosteroids (ICS). To encourage patient adherence, two classes of medication are often combined in a single medication device; it seems that once-daily dosing offers greatest convenience to patients and may markedly influence adherence. Objectives To compare a once-daily combination of inhaled corticosteroid and long-acting beta₂-agonist inhalers (ICS/LABA) versus inhaled long-acting muscarinic antagonists alone (LAMA) for people with chronic obstructive pulmonary disease (COPD). Search methods We performed an electronic search of the Specialised Register of the Cochrane Airways Group (14 May 2018), ClinicalTrials.gov (14 May 2018), and the World Health Organization International Clinical Trials Registry Platform (20 September 2017), then a search of other resources, including reference lists of included studies and manufacturers' trial registers (10 October 2017). Two pairs of review authors screened and scrutinised selected articles. Selection criteria We included randomised controlled trials (RCTs) comparing once-daily administered ICS/LABA and LAMA in adults with COPD. Data collection and analysis Two review authors independently extracted data and assessed risk of bias in each study. We analysed dichotomous data as random-effects odds ratios (ORs) and continuous data as mean differences (MDs), both with 95% confidence intervals (95% CIs), using Review Manager 5. Main results We included two studies with 880 participants. We identified one ongoing trial with planned recruitment of 80 participants. Included studies enrolled participants with both partially reversible and non-reversible COPD and baseline mean per cent predicted (%pred) forced expiratory volume in one second (FEV₁) of 43.4 to 49.6. Both studies lasted 12 weeks. Both studies used the same combination of inhaled ICS/LABA (fluticasone furoate and vilanterol 100/25 mcg once daily; FF/VI) versus LAMA (18 mcg tiotropium; TIO). They were published as full articles, and neither study was at low risk of bias in all domains.Compared to the TIO arm, results for pooled primary outcomes for the FF/VI arm were as follows: mortality: OR 0.20, 95% CI 0.02 to 1.73, 880 participants (deaths reported only in the TIO arm), very low-quality evidence; COPD exacerbation (requiring short-burst oral corticosteroids or antibiotics, or both): OR 0.72, 95% Cl 0.35 to 1.50, 880 participants, very low-quality evidence; pneumonia: reported in both studies only during treatment with FF/VI: OR 6.12, 95% Cl 0.73 to 51.24, 880 participants, very low-quality evidence; and total serious adverse events: OR 0.96, 95% Cl 0.50 to 1.83, 880 participants, very low-quality evidence. None of the pneumonias were fatal. Compared to the TIO arm, we found no statistically significant difference for pooled secondary outcomes, including St George's Respiratory Questionnaire (SGRQ) mean total score change; hospital admissions (all-cause); disease-specific adverse events; mean weekly rescue medication use (results available from only one of the studies); and mean weekly percentage of rescue-free days for FF/VI. We found no statistically significant differences between ICS/LABA and LAMA for improvement in symptoms measured by the COPD Assessment Test (CAT score) nor for FEV₁ (change from baseline trough in 24-hour weighted mean on treatment day 84). Many pooled estimates lacked precision. Data for other endpoints such as exacerbations leading to intubation and physical activity measures were not available in included trials. Authors' conclusions Based on analysis of primary and secondary outcomes, we are uncertain whether once-daily ICS/LABA, combined in one inhaler, has a different efficacy or adverse effect profile compared to LAMA for treatment of people with COPD. However, the current review is based on only two trials with the main focus on primary outcomes other than those considered in this review. The short follow-up period and the very low quality of evidence limit our confidence in the result and increase uncertainty. Further trials of longer duration are needed. Current evidence is not strong enough to demonstrate important differences between inhalers in terms of effects, nor to establish that once-daily fluticasone/vilanterol 100/25 mcg and tiotropium 18 mcg are equivalent.

An Electronic Diary Is Shown to Be More Reliable than a Paper Diary: Results from a Randomized Crossover Study in Patients with Persistent Asthma

Objectives. Test–retest reliability of an asthma paper diary versus an electronic diary (e-diary) with an integrated peak flow meter was investigated. The equivalence of the two modes was also evaluated. Methods. Prospective, randomized crossover study design in adolescents (12–17 years) and adults (≥18 years). Key inclusion criteria were persistent asthma, Asthma Control Test (ACT) scores ≥16, use of inhaled corticosteroid with or without long-acting beta-agonist for ≥12 weeks, nocturnal awakenings <2 times in the past week, and activity limitations <1 per week. Participants were randomized to either paper then e-diary or e-diary then paper, to be completed for 14 days each. Results. Forty-seven participants completed all study visits. Weekly percentage of symptom-free days (SFDs) and rescue-free days (RFDs) were calculated. Intraclass correlation coefficients (ICCs) of Week 1 mean SFD and RFD (test) and Week 2 mean SFD and RFD (retest), respectively, were estimated in three groups defined as stable: (i) minimal changes in asthma symptoms, as measured by the global patient reported symptom change question, (ii) less than 15% change (absolute value) in 1 second FEV1 at adjacent study visits, and (iii) changes in ACT scores less than three points for each mode. SFD demonstrated acceptable ICC (≥0.70) using all three definitions of asthma stability for both modes. Conclusion. Acceptable reproducibility of the percentage of RFD (ICC = 0.78) was only observed for the e-diary using the FEV1 stability criterion. The ICCs for SFD and RFD were acceptable, 0.84 and 0.70, respectively, suggesting better reliability for the e-diary.

Efficacy and Tolerability of Indacaterol 75 μg Once Daily in Patients Aged ≥40 Years With Chronic Obstructive Pulmonary Disease: Results From 2 Double-Blind, Placebo-Controlled 12-Week Studies

Background Indacaterol is the first once-daily, long-acting, inhaled β 2-agonist bronchodilator for maintenance treatment of chronic obstructive pulmonary disease (COPD). Two studies (previously reported in a Congress abstract) were performed in 2010 to provide efficacy and tolerability data to support the application for approval in the United States of indacaterol 75 μg once daily, a dose lower than that previously investigated in most studies. Objective The primary objective was to evaluate the efficacy of indacaterol 75 μg once daily in terms of 24-hour post-dose (“trough”) forced expiratory volume in the first second of respiration (FEV 1) compared with placebo after 12 weeks of treatment. Methods Patients with moderate to severe COPD were randomized to receive double-blind treatment with indacaterol 75 μg once daily (n = 163 and 159) or placebo (n = 160 and 159) for 12 weeks. In addition to trough FEV 1 after 12 weeks, rescue albuterol use, health status (St. George's Respiratory Questionnaire [SGRQ]), and tolerability were evaluated. Clinically relevant differences between active and placebo treatments were defined as ≥120 mL for trough FEV 1 and a decrease of ≥4 units in SGRQ total score. Results Of patients enrolled in the 2 studies, 54% were men, and 90% and 94% were white, with mean age 64 and 61 years. Mean duration of COPD was 7 years; smoking history was 52 pack-years; and 45% and 37% of patients were receiving inhaled corticosteroid therapy. At week 12, indacaterol demonstrated clinically relevant bronchodilator efficacy, increasing trough FEV 1 by ≥120 mL versus placebo ( P < 0.001), with significant bronchodilation maintained at all time points from 5 minutes to 24 hours post-dose. Over 12 weeks, relative to placebo, in patients receiving indacaterol therapy, rescue albuterol use was reduced by 1.2 and 0.7 puffs per day ( P < 0.01), and the percentage of rescue-free days was increased by 13.7 and 8.4 ( P < 0.01). At week 12, the SGRQ total score differed in the indacaterol group versus the placebo group by −3.8 and −3.6, respectively ( P ≤ 0.01). Adverse events were reported for 49% and 45% of patients receiving indacaterol therapy, and for 46% and 41% receiving placebo. Conclusions Compared with placebo, indacaterol 75 μg once daily provided statistically significant and clinically relevant 24-hour bronchodilation and was well tolerated. In patients receiving indacaterol, the reduction in rescue albuterol use was statistically significant. Changes in health status also were statistically significant compared with placebo, although the differences of 3.6 and 3.8 units were below the predefined 4-unit level of clinical relevance. The results of these studies suggest that indacaterol 75 μg once daily is an effective maintenance treatment in patients with moderate to severe COPD. ClinicalTrials.gov identifiers: NCT01072448 and NCT01068600.

Short-term and long-term asthma control in patients with mild persistent asthma receiving montelukast or fluticasone: a randomized controlled trial

Purpose To determine whether montelukast is as effective as fluticasone in controlling mild persistent asthma as determined by rescue-free days. Subjects and methods Participants aged 15 to 85 years with mild persistent asthma (n = 400) were randomized to oral montelukast (10 mg once nightly) or inhaled fluticasone (88 μg twice daily) in a year-long, parallel-group, multicenter study with a 12-week, double-blind period, followed by a 36-week, open-label period. Results The mean percentage of rescue-free days was similar between treatments after 12 weeks (fluticasone: 74.9%, montelukast: 73.1%; difference = 1.8%, 95% confidence interval [CI]: −3.2% to 6.8%) but not during the open-label period (fluticasone: 77.3%, montelukast: 71.1%; difference = 6.2%, 95% CI: 0.8% to 11.7%). Although both fluticasone and montelukast significantly improved symptoms, quality of life, and symptom-free days during both treatment periods, greater improvements occurred with fluticasone in lung function during both periods and in asthma control during open-label treatment. Post hoc analyses revealed a difference in rescue-free days favoring fluticasone in participants in the quartiles for lowest lung function and greatest albuterol use at baseline. Conclusion In patients with mild persistent asthma, rescue-free days and most asthma control measures improved similarly with fluticasone or montelukast over the short term, but with prolonged open-label treatment, asthma control improved more with fluticasone. Improved asthma control with fluticasone appeared to occur in those with decreased lung function and greater albuterol use at baseline. In the remaining patients, the two treatments appeared to be comparable. These results suggest that classification criteria for mild persistent asthma may need to be re-evaluated.

Salmeterol Powder Provides Significantly Better Benefit Than Montelukast in Asthmatic Patients Receiving Concomitant Inhaled Corticosteroid Therapy

Comparison of inhaled salmeterol powder vs oral montelukast treatment in patients with persistent asthma who remained symptomatic while receiving inhaled corticosteroids. Randomized, double-blind, double-dummy, parallel-group, multicenter trials of 12-week duration. Outpatients in private and university-affiliated clinics. Male and female patients > or = 15 years of age with a diagnosis of asthma (baseline FEV(1) of 50 to 80% of predicted) and symptomatic despite receiving inhaled corticosteroids. Inhaled salmeterol xinafoate powder, 50 microg bid, or oral montelukast, 10 mg qd. Treatment with salmeterol powder resulted in significantly greater improvements from baseline compared with montelukast for most efficacy measurements, including morning peak expiratory flow (35.0 L/min vs 21.7 L/min; p < 0.001), percentage of symptom-free days (24% vs 16%; p < 0.001), and the percentage of rescue-free days (27% vs 20%; p = 0.002). Total supplemental albuterol use was decreased significantly more in the salmeterol group compared with the montelukast group (- 1.90 puffs per day vs - 1.66 puffs per day; p = 0.004) and nighttime awakenings per week decreased significantly more with salmeterol than with montelukast (- 1.42 vs - 1.32; p = 0.015). Patients treated with inhaled salmeterol were significantly more satisfied with their treatment regimen and how well, how fast, and how long it worked than were patients who were treated with oral montelukast. The safety profiles for the two treatments were similar. In patients with persistent asthma who remain symptomatic while receiving inhaled corticosteroids, adding inhaled salmeterol powder provided significantly greater improvement in lung function and asthma symptoms and was preferred by patients over oral montelukast.

Analysis of montelukast in mild persistent asthmatic patients with near-normal lung function

Few studies have specifically evaluated controller therapy in patients with mild persistent asthma. We used a subgroup analysis to investigate the effects of montelukast, a potent cysteinyl leukotriene receptor antagonist, on adult patients on the milder end of the asthma severity spectrum. We have identified seven double-blind, randomized, placebo-controlled studies of adult patients with mild-to-moderate chronic asthma in which montelukast was investigated. Subsets of patients with baseline forced expiratory volume in 1 sec (FEV1) >80% and >75% predicted or further restricted by less than daily rescue β -agonist use were included as four cohorts (A, B, C, D), and efficacy measures, including change in FEV1rescue-free days, β -agonist use, nocturnal awakenings and blood eosinophil counts were evaluated. Cohorts A to D comprised 21%, 8%, 11%, and 4%, respectively, of patients from these studies. Mean pretreatment FEV1ranged from 81% to 84% predicted and daily β -agonist use from 2·4 to 4·5 puffs day−1in the four cohorts. Pooled results demonstrated a treatment effect for montelukast over placebo in all cohorts, for all endpoints. There was a significant improvement in FEV1in montelukast-treated patients (7–8% over baseline) compared with placebo (1–4% over baseline, between-group difference P≤0·02) for all cohorts. Similarly, the percentage of rescue-free days increased substantially more with montelukast (22–30%) than with placebo (8–13%). This subgroup analysis indicates that montelukast produced improvements in parameters of asthma control in patients with milder persistent asthma that should be confirmed in additional prospective trials.

Fluticasone propionate versus zafirlukast: effect in patients previously receiving inhaled corticosteroid therapy

The use of inhaled corticosteroids compared with leukotriene modifying drugs in the treatment of persistent asthma has not been extensively studied. To compare the efficacy and safety of a low dose of fluticasone propionate (FP) and zafirlukast in patients previously maintained on inhaled corticosteroids. Patients (> or = 12 years old; FEV1 = 60% to 85% of predicted) with persistent asthma who were previously treated with low doses of triamcinolone acetonide (TAA) 400 to 800 microg/day or beclomethasone dipropionate (BDP) 168 to 336 microg/day were randomized to treatment with FP aerosol 88 microg BID (FP, n = 221) or zafirlukast 20 mg BID (n = 216) over 6 weeks. Treatment with FP significantly increased the mean change at endpoint (the last post-baseline observation) in FEV1 (0.22 L versus 0.03 L, P < .001), morning PEF (17.8 versus 3.1 L/min, P = .004), evening PEF (16.7 versus 2.6 L/min, P = .002), the percentage of symptom-free days (16.2 versus 7.1%, P = .007), and the percentage of rescue-free days (23.4 versus 9.3%, P < .001), and significantly decreased rescue albuterol use (-0.66 puffs/day versus an increase of 0.27 puffs/day, P < .001) and combined symptom scores (-0.13 versus an increase of 0.08, P < .001) compared with zafirlukast. Treatment with FP maintained the percentage of awakening-free nights (-1.0 +/- 1.0); in contrast, treatment with zafirlukast reduced the percentage of awakening-free nights (-9.0 +/- 1.6, P < .001). A clinically meaningful difference (change of > or = 0.5; P < .001) was observed between FP and zafirlukast in the Asthma Quality of Life Questionnaire (AQLQ) global score and for each domain score except activity limitation (change of 0.3, P < .001). Significantly more patients in the zafirlukast group experienced an asthma exacerbation (n = 14) compared with FP-treated patients (n = 5, P = .035). Patients in the zafirlukast group were significantly more likely to be withdrawn due to lack of efficacy (P < .001). Switching patients from low doses of inhaled corticosteroids to a lower total microgram dose of FP improves pulmonary function, asthma symptoms, and quality of life, while switching to the leukotriene receptor antagonist zafirlukast may result in worsening of asthma control. This was indicated by the significant number of zafirlukast-treated patients who were dropped from the study due to lack of efficacy within 6 weeks of discontinuing inhaled corticosteroids.

Low-dose inhaled fluticasone propionate versus oral zafirlukast in the treatment of persistent asthma

Background: Few studies have compared the efficacy of inhaled corticosteroids and leukotriene modifiers for the treatment of persistent asthma. Objective: Our purpose was to compare the efficacy of a low dose of inhaled fluticasone propionate (FP) with that of oral zafirlukast in the treatment of persistent asthma previously treated with short-acting β 2-agonists alone. Methods: A 12-week, randomized, double-blind, double-dummy, multicenter study was conducted in 451 patients aged 12 years and older with asthma who were symptomatic on short-acting β 2-agonists alone. After an 8- to 14-day run-in period, patients were randomized to treatment with FP 88 μg twice daily or zafirlukast 20 mg twice daily. Results: Treatment with FP was more effective than treatment with zafirlukast in increasing morning FEV 1 (by 0.42 L vs 0.20 L over baseline, P < .001), morning peak expiratory flow (by 49.94 L/min vs 11.68 L/min over baseline, P < .001), and evening PEF (by 38.91 L/min vs 10.50 L/min over baseline, P < .001). Statistically significant differences between the two treatments in FEV 1 were noted after the first observation (week 4) and in morning and evening peak expiratory flow by week 2. Mean change in percentage of symptom-free days was greater with FP than with zafirlukast (28.5% of days vs 15.6% of days, P < .001) and FP significantly increased the percentage of rescue-free days by 40.4% of days compared with 24.2% of days with zafirlukast ( P < .001). Treatment with FP significantly reduced albuterol use by 2.39 puffs per day compared with 1.45 puffs per day ( P < .001) and increased the percentage of nights with no awakenings by 21.2% of nights compared with 8.0% of nights with zafirlukast ( P < .001). Conclusion: The clinical effectiveness of a low dose of FP as first-line therapy in patients with persistent asthma who are symptomatic on β 2-agonists alone is superior to that of zafirlukast. (J Allergy Clin Immunol 2000;105:1123-9.)

A Study on the Clinical Equivalence and Patient Preference of Fluticasone Propionate 250 μg Twice Daily via the DiskusTM/AccuhalerTM Inhaler or the DiskhalerTM* Inhaler in Adult Asthmatic Patients

The DiskusTM/AccuhalerTM inhaler (D/A) is a new multidose powder inhaler, designed to deliver all asthma drugs. This study was carried out to establish clinical equivalence between FP 250 μg twice daily (b.i.d.) via the D/A and FP 250 μg b.i.d. via the current powder inhaler, the Diskhaler (DH). Also, device handling and patient preference for both devices were determined. This was a multicenter, randomized, double-blind, double-dummy, parallel-group study. Adult asthmatics (364, aged 18–79) requiring inhaled corticosteroids in a daily dosage of 400 μg up to and including 1000 μg and demonstrating a mean morning peak expiratory flow rate (PEFR) calculated from the last 7 days of the run-in of less than 85% of the response after salbutamol, a baseline forced expiratory volume in 1 sec (FEV1 between 50 and 90% of their predicted normal value, and an ability to correctly use both devices, were randomized to a 12-week treatment period. No statistically significant differences between the two devices were seen for mean morning PEFR (p = 0.76), mean evening PEFR (p = 0.88), median daytime and nighttime symptom score (p = 0.57 and p = 0.47), median percentage of rescue-free days and nights (p = 0.43 and p = 0.24), and clinic visit lung function. No differences in the safety profile of FP were seen. Patients found the D/A easier to use and easier with respect to assessing the number of doses remaining (both p < 0.001). Sixty-five percent of the patients expressed an overall preference for the D/A over the DH (p < 0.001). The results show that FP 250 μg b.i.d. via the D/A is clinically equivalent to delivery via the DH. Both treatments proved to be equally safe and were well tolerated. The D/A was easier to use and patients preferred the D/A over the DH.