Leukotriene Receptor Antagonists— Monotherapy/Effectiveness Studies

July 2007

Evidence Table 14. Pharmacologic Therapy: Leukotriene Receptor Antagonists— Monotherapy/Effectiveness Studies

Abbreviations used in table: AE adverse event ICS inhaled corticosteroid BCD (or B) beclomethasone dipropionate ITT intent-to-treat CPAP continuous positive airway pressure LTRA leukotriene receptor antagonist ECP eosinophil cationic protein M montelukast

FEF25%–75% forced midexpiratory flow PC20 provocative concentration causing a 20% fall in FEV1

FEV1 forced expiratory volume in 1 sec. PEF peak expiratory flow FP (or F) fluticasone propionate QoL quality of life FVC forced vital capacity RFD rescue-free days GINA Global Initiative for Asthma Guidelines SAE severe adverse event

* indicates primary outcome

1 July 2007

Evidence Table 14. Pharmacologic Therapy: Leukotriene Receptor Antagonists— Monotherapy/Effectiveness Studies

Study Population Citation Study N Asthma Severity at Baseline (Sponsor) Study Design (Number Evaluable) Population Characteristics (If Reported) Malmstrom et al. (for the Multicenter, randomized, 895 Age Chronic asthma Montelukast/Beclomethasone double-dummy, placebo-controlled, (895?; all patients at least 15–85 yr, median 35 yr Duration 0.5–67 yr, median 17 yr Study Group). Oral montelukast, parallel-group trial followed by a 1 measurement after baseline) Gender 10% using theophylline inhaled beclomethasone, and double-blind placebo washout period 40% male, 60% female 63% with history of allergic rhinitis placebo for chronic asthma: a (36 clinical centers in 19 countries; randomized, controlled trial. Ann analyses adjusted for investigator Ethnicity 79% with history of exercise-induced asthma Intern Med 1999;130(6):487–495. effect) Caucasian 52%, Hispanic 32%, other 16% FEV1, mean = 2.2 L (Merck Research Laboratories) FEV1 % pred., mean = 65 Morning PEF, mean = 335 L/min Evening PEF, mean = 353 L/min Daytime asthma symptom score, mean = 3.4 (scale 0–6)

Beta2-agonist use, mean = 5.5 puffs/day Nocturnal awakenings, mean = 5.5 nights/week Eosinophil count, mean = 0.36 cells x 103/mcL

Bisgaard and Nielsen. Randomized, placebo-controlled, 16 Age Hyperresponsive to cold, dry air challenge Bronchoprotection with a crossover study (13 in ITT analysis) 3.1–5.7 yr, mean = 4.5 yr Duration of asthma 4–62 months, mean = 39 months leukotriene receptor antagonist in (Study was repeated with 6 of original Gender Specific airway resistance, range 1.36–2.25, asthmatic preschool children. Am J sample to evaluate consistency of 69% male, 31% female mean = 1.71 kPa Respir Crit Care Med treatment response.) 2000;162(1):187–190. Ethnicity % pred. range 103%–170%, mean = 129% Not reported 62% used inhaled budesonide, mean daily dose = 350 mcg Treatment regimen was unchanged for at least 2 months prior to study 54% had first-degree relative with atopic disease. 38% had concurrent atopic dermatitis. 23% had hay fever. 23% were exposed to passive smoking at home.

2 July 2007

Study Population Citation Study N Asthma Severity at Baseline (Sponsor) Study Design (Number Evaluable) Population Characteristics (If Reported) Bleecker et al. Low-dose inhaled Multicenter, randomized, double-blind, 451 Age Persistent asthma fluticasone propionate versus oral double-dummy trial (ITT) 12–68 yr, mean = 31 yr Duration >6 months zafirlukast in the treatment of Gender FEV , mean = 2.5 L persistent asthma. J Allergy Clin 1 Immunol 2000;105(6 Pt 1): 1123– 50% male, 50% female PEF, mean = 362 L/min 1129. Ethnicity Albuterol use, mean = 4.67 puffs/day (GlaxoWellcome, Inc.) Caucasian 83%, African American 8%, other 9% Symptom score, mean = 1.15 Smoking No use of tobacco within the previous yr or a smoking history of >10 pack-yr

Busse et al. (for the Fluticasone Multicenter, randomized, double-blind, 533 Age Persistent asthma Propionate Clinical Research Study double-dummy, parallel-group study (ITT analysis) 15–83 yr, mean = 34.9 yr Duration >6 months Group). Low-dose fluticasone (52 study sites; analyses adjusted for Gender FEV1 % pred., range 50%–80%, mean = 65.5% propionate compared with site) montelukast for first-line treatment 44.8% male, 55.2% female All used short-acting beta2-agonist for 3 months before of persistent asthma: a randomized Ethnicity screening. clinical trial. J Allergy Clin Immunol 83% White, 10% African American, 7% other Symptom score, mean = 1.67 (0–5 range) 2001;107(3):461–468. (GlaxoWellcome, Inc.)

Busse et al. Fluticasone propionate Multisite, randomized double-blind, 338 Age Persistent asthma; majority had moderate asthma compared with zafirlukast in double-dummy, parallel-group study (ITT analysis) 12–75 yr Most had asthma diagnosed for >10 yr. controlling persistent asthma: a (34 sites in the United States; analyses Gender FEV1, mean = 2.44 L randomized double-blind, adjusted for investigator effect) placebo-controlled trial. J Fam 50% male, 50% female Morning PEF, mean = 349 L/min Pract 2001;50(7):595–602. Ethnicity Evening PEF, mean = 382 L/min (GlaxoWellcome, Inc.) Non-Hispanic White 86%, African American 10%, All had used short-acting beta2-agonist at least 6 weeks. other 4% Albuterol use, mean = 4.9 puffs/day Albuterol-free days, mean = 5.8% Symptom score, mean = 1.36 (0–5 range)

3 July 2007

Study Population Citation Study N Asthma Severity at Baseline (Sponsor) Study Design (Number Evaluable) Population Characteristics (If Reported) Nathan et al. A comparison of Multisite, randomized, double-blind, 294 Age Persistent asthma short-term treatment with inhaled parallel-group study (294) 12–70 yr, mean = 32 yr Morning predose FEV1, mean = 2.5 L fluticasone propionate and (25 centers in the United States; Gender FEV1 % pred., mean = 68.5 zafirlukast for patients with analyses adjusted for site) persistent asthma. Am J Med 44% male, 56% female Morning PEF, 352 L/min 2001;111(3):195–202. Ethnicity Evening PEF, mean = 389 L/min (GlaxoWellcome, Inc.) Caucasian 85%, African American 10%, other 5% Use of inhaled or oral short-acting beta2-agonist for >6 weeks Daily albuterol use, mean = 4.4 puffs/day

Storms et al. Clinical safety and Pooled analysis from 11 multicenter, 3,386 and 336 pediatric Trials: Adults Chronic asthma: mild, moderate, and severe persistent tolerability of montelukast, a randomized, controlled Phase IIb and patients in trials; 2,031 adults Age Allergic rhinitis history: 77% of adults, 94% of children leukotriene receptor antagonist, in Phase III trials and 5 long-term and 257 children in extension 15–85 yr, mean = 37 yr FEV % pred., range 40–90 controlled clinical trials in patients extension studies studies 1 aged > or = 6 years. Clin Exp Gender Allergy 2001;31(1):77–87. 49% male, 51% female (Merck and Co., Inc.) Ethnicity Caucasian 79%, Hispanic 12%, Black 4%, other 6% Trials: Children Age 6–15 yr, mean = 11 yr Gender 65% male, 35% female Ethnicity Caucasian 80%, Hispanic 4%, Black 13%, other 3% (Similar percentages of each demographic group entered into the extensions.)

Brabson et al. Efficacy and safety Multicenter randomized double-blind, 440 Age Stable persistent asthma of low-dose fluticasone propionate double-dummy trial (378; ITT) >12 yr, mean = 35.5 yr Fixed daily dose of inhaled BCD 168–336 mcg compared with zafirlukast in (44 sites in the United States) Gender (mean = 263 mcg) or triamcinolone acetonide 400–800 mcg patients with persistent asthma. Am (mean = 602 mcg) J Med 2002;113(1):15–21. 37% male, 63% female Ethnicity 38% treated by primary care physician; 52% treated by (GlaxoWellcome, Inc.) specialist Caucasian 81%, Black 4%, other 15% FEV1 % pred., mean = 73 PEF, mean = 87%

4 July 2007

Study Population Citation Study N Asthma Severity at Baseline (Sponsor) Study Design (Number Evaluable) Population Characteristics (If Reported) Israel et al. Effects of montelukast Multicenter, randomized, double-blind, 782 Age Persistent asthma and beclomethasone on airway placebo-controlled, parallel-group study (752; ITT) 15–74 yr, mean = 33.2 yr Duration >1 yr, mean = 19 yr function and asthma control. (64 centers in the United States) Gender FEV , mean = 2.5 L J Allergy Clin Immunol 1 2002;110(6):847–854. 48% male, 52% female FEV1, % pred., mean = 66.7 (Merck and Co., Inc., Whitehouse Ethnicity Reversibility %, mean = 28.8 Station, NJ; and USHH-Merck and Caucasian 85%, Black 6%, Hispanic 5%, other 4% Daily beta2-agonist use, mean = 5.7 puffs/day Co., Inc., West Point, PA) Smoking Nonsmoker for >1 yr with smoking history <7 pack-yr Kanniess et al. Montelukast versus Randomized, double-blind, crossover 40 Age Moderate, allergic bronchial asthma fluticasone: effects on lung design (40) 18–60 yr, mean = 37 yr No ICS or systemic corticosteroids within 3 or 6 months or function, airway responsiveness Gender antihistamines or theophylline within 4 weeks and inflammation in moderate FEV , mean = 2.79 L asthma. Eur Respir J 60% male, 40% female 1 2002;20(4):853–858. Ethnicity FEV1 % pred., mean = 74.0 (GlaxoSmithKline, Germany) Not reported FVC % pred., mean = 93.1 Smoking PC20 methacholine (Mch) geometric mean = 0.180 mg/mL 100% nonsmokers Sputum eosinophils, geometric mean = 4.28% Tryptase in sputum, geometric mean = 8.0 pg/mL

Baumgartner et al. Distribution of Multicenter, randomized, double-blind, 730 Age Chronic asthma therapeutic response in asthma double-dummy, placebo-controlled, (679; ITT for efficacy) >15 yr, mean = 35.7 yr Duration >1 yr, mean = 18.6 yr control between oral montelukast parallel group study Gender FEV1, mean = 2.21 L and inhaled beclomethasone. Eur (16 centers in 8 countries) Respir J 2003;21(1):123–128. 34% male, 66% female FEV1 % pred., mean = 68 Ethnicity Beta-agonist use, mean = 5.2 puffs/day Not reported Smoking Nonsmokers for >1 yr

5 July 2007

Study Population Citation Study N Asthma Severity at Baseline (Sponsor) Study Design (Number Evaluable) Population Characteristics (If Reported) Bisgaard. A randomized trial of Multicenter randomized, double-blind, 130 Age Moderate-to-severe symptoms requiring hospital admission montelukast in respiratory syncytial placebo-controlled, parallel-group study (116 for treatment period, 87 3–36 months, mean = 9.5 months Admission 2–7 days, median 4.5 days virus post-bronchiolitis. Am J (11 pediatric centers that were for followup period) Gender Treatment: O2, 29%; CPAP, 16%; beta-agonist, 81% Respir Crit Care Med secondary referral centers) 2003;167(3):379–383. 48% male, 52% female (University Hospital of Ethnicity Copenhagen, Denmark) Not reported Tobacco exposure, 42% Pets at home, 43% Atopic heredity, 38%

Ducharme. Inhaled glucocorticoids Systematic review of randomized 13 trials; 5,109 subjects Age 4 trials focused on patients with mild asthma. versus leukotriene receptor controlled trials Sample sizes ranged from 20 1 pediatric trial with mean age = 10 yr; 12 adult trials 8 trials had patients with moderate obstruction. antagonists as single agent asthma (All were parallel group designs; 10 to 666, with mean of 393 with mean age ranging from 30 to 41 yr 1 trial failed to report severity. treatment: systematic review of used double-blinding, while 3 were Gender current evidence. BMJ open label; 10 were of high Males ranged from 35% to 65% in the various trials 2003;326(7390):621–625. methodological quality.) Ethnicity Not reported Smoking Not reported

Jayaram et al. Steroid naive Multicenter, randomized, double-blind, 50 Age Persistent symptomatic asthma eosinophilic asthma: anti- double-dummy, parallel group placebo (49) 34.7 yr Had taken only short-acting bronchodilator for at least inflammatory effects of fluticasone and active controlled trial Gender 2 months and montelukast. Thorax (4 centers) FEV % pred., 75.9 (prebronchodilator) 2005;60(2):100–105. 41% male, 59% female 1 Change in FEV after bronchodilator, mean = 18.8% (GlaxoWellcome, Inc.) Ethnicity 1 Not reported 86% atopic Smoking Salbutamol use, mean = 3.1 puffs/day 10% current smoker, 14% exsmoker, 76% nonsmoker Symptom score, mean = 24.0 (range 5–35) All had induced sputum eosinophilia >3.5%.

6 July 2007

Study Population Citation Study N Asthma Severity at Baseline (Sponsor) Study Design (Number Evaluable) Population Characteristics (If Reported) Jenkins et al. Traditional and Randomized double-blind, double- 58 Age Mild-to-moderate persistent, suboptimally controlled asthma patient-centered outcomes with dummy crossover design (53) 16–70 yr, mean = 38.5 yr 67% taking ICS prior to enrollment three classes of asthma Gender FEV % pred., mean = 76.1 medication. Eur Respir J 1 2005;26(1):36–44. 60% male, 40% female FEV1/FVC ratio, mean = 0.72 (Australian Federal Government, Ethnicity AstraZeneca, Aventis Pharma, Not reported GlaxoSmithKline, Merck Sharp and Smoking Dohme, New South Wales State 19% former smokers Department of Health)

Straub et al. The effect of Randomized, double-blind, placebo- 24 Age Mild disease activity montelukast on lung function and controlled trial (24) Mean = 18.3 months FEV0.5, 175 mL exhaled nitric oxide in infants with Gender Symptom score, range 0–9; median = 4.5 (possible range, early childhood asthma. Eur Respir 0–18) J 2005;25(2):289–294. 54% male, 46% female Ethnicity Fractional exhaled nitric oxide, mean = 31.6 ppb Not reported Sensitive only to food allergens, 66.7%; sensitive only to aeroallergens 16.7%; and sensitive to both food and aeroallergens, 16.7% All had history of recurrent wheeze. All had positive family history of asthma.

Garcia-Garcia et al. Montelukast, Multicenter, randomized, double-blind, 994 Age Mild persistent at step 2 of GINA guidelines compared with fluticasone, for double-dummy, parallel-group design (966; intent-to-treat analysis) 5–15 yr, median 9 yr Clinical history of >12 months control of asthma among 6- to 14- (104 sites in 24 countries) Gender 61.7% had history of allergic rhinitis. year-old patients with mild asthma: the MOSAIC study. Pediatrics 62% male, 38% female FEV1 % pred., range 34–129, median = 86.8 2005;116(2):360–369. Ethnicity FEV1 range, 0.5–4.6 L; median = 1.8 L (Merck and Co.) 63.6% White, 21.2% Hispanic, 5.9% Asian, 0.6% Black, During 4-week run-in: asthma RFDs, range 0%–100%, 7.2% multiracial, 1.5% other median = 64%; days with beta-receptor agonist use, range Weight 0%–100%, median = 35.6% 106–181 kg, median 136 kg Height 106–181 cm, median 135 cm

7 July 2007

Study Population Citation Study N Asthma Severity at Baseline (Sponsor) Study Design (Number Evaluable) Population Characteristics (If Reported) Ostrom et al. Comparative efficacy Multisite randomized, double-blind, 342 Age Persistent asthma and safety of low-dose fluticasone double-dummy, parallel-group study (ITT analysis) 5–12 yr, mean = 9.3 yr Duration >6 months propionate and montelukast in (43 clinical centers in the United States; Gender FEV1 % pred., range 60%–85%, mean = 75.9% children with persistent asthma. investigator controlled in analysis) J Pediatr 2005;147(2):213–220. 65% male, 35% female FEV1, mean = 1.65 L (GlaxoSmithKline, Inc.) Morning PEF, mean = 230 L/min Evening PEF, mean = 242 L/min

All used short-acting beta2-agonist over the 3 months before screening. Daytime asthma symptom score, mean = 1.59 (0–5 range) Nighttime asthma symptom score, mean = 0.69 (0–3 range) % symptom-free days, mean = 18.8 Total albuterol use: mean = 2.39 puffs/day; daytime mean = 1.73 puffs/day; nighttime mean = 1.65 puffs/day % RFDs, mean = 25.4

Szefler et al. Characterization of Randomized crossover study 144 Age Mild-to-moderate asthma within-subject responses to (126) 6–17 yr Improvement in FEV1 of 12% or greater after maximal fluticasone and montelukast in Gender bronchodilation or methacholine PC20 of 12.5 mg/mL or less childhood asthma. J Allergy Clin No corticosteroid treatment within 4 weeks, no leukotriene- Immunol 2005;115(2):233–242. Not reported Ethnicity modifying agents within 2 weeks, no history of respiratory (National Heart, Lung, and Blood tract infection within 4 weeks Not reported Institute) Asthma symptoms or rescue bronchodilator use, on average, 3 or more days/week during previous 4 weeks

Zeiger et al. Short-term and long- Multicenter, randomized, 2-part, 400 Age Mild persistent asthma term asthma control in patients with parallel-group trial (176 in ITT analysis for 15–85 yr, mean = 35.2 yr Age at first treatment, mean = 20.6 yr mild persistent asthma receiving (39 sites) double-blind period; 329 for Gender Atopy, 80% montelukast or fluticasone: a open-label period) Mild Asthma Montelukast versus 31% male, 69% female FEV1, mean = 3.3 L randomized controlled trial. Am J Inhaled Corticosteroid (MIAMI) study Med 2005;118(6):649–657. Ethnicity FEV1 % pred., mean = 94 (Merck & Co., Inc.) 80.8% White, 7.9% Black, 2.6% Asian, 8.7% other Albuterol use, mean = 3.5 days/week Daytime asthma symptoms, mean = 3.6 days/week Nighttime awakenings, 65.5% <2/month, 34.5% >2/month RFDs, mean = 58.1% of days in run-in period

8 July 2007

Study Population Citation Study N Asthma Severity at Baseline (Sponsor) Study Design (Number Evaluable) Population Characteristics (If Reported) Zeiger et al. Response profiles to Multicenter, double-blind, randomized, 144 Age Mild-to-moderate persistent asthma fluticasone and montelukast in crossover trial (127) 6–17 yr with 33% 6–9 yr Absence of leukotriene modifier agents within 2 weeks mild-to-moderate persistent (Stratified by clinical center, age, and In previous 4 weeks: asthma symptoms or rescue Gender childhood asthma. J Allergy Clin FEV1 percent predicted) bronchodilator use on average of 3 or more days/week, no Immunol 2006;117(1):45–52. 59% male, 41% female corticosteroid therapy, no respiratory tract infection (National Heart, Lung, and Blood Ethnicity FEV1 % pred. >70% Institute) 48% minority >12% FEV1 reversibility after maximum bronchodilation or methacholine dose required to reduce baseline FEV1 by 20%

9 July 2007

Study Characteristics Findings Duration of Active Treatment; Duration of Postintervention/ Citation Off-Treatment Exacerbations/ (Sponsor) Treatment Dose Followup Rescue Medication Use Lung Function Symptoms Adverse Events Malmstrom et al. (for Purpose/Objective: To compare the clinical benefit of montelukast Mean difference between *Mean differences between Mean differences between B the Montelukast/ (M), placebo (P), and inhaled beclomethasone (B) B treatment and M treatment B and M treatment were 5.8% and M treatment groups were Beclomethasone for beta-agonist use was (95%CI 3.0% to 8.5%) for –0.21 (95%CI –0.33 to –0.09) Arm 1 10 mg once daily in 12-week trial after a 2- Study Group). Oral –0.67 puffs/day (95% CI FEV1, 15.4 L/min (95% CI 8.1 for daytime symptom scores montelukast, inhaled M + placebo inhaler evening + 2 puffs week, single-blind –1.10 to –0.245 puffs/day). to 22.5 L/min) for morning and –0.70 (95% CI –1.098 to beclomethasone, (n=387; from inhaler at placebo run-in period. PEF, and 11.2 L/min (95% CI –0.32) for nocturnal and placebo for 354 completers) bedtime and in Period 3 was a 3-week, 4.2 to 18.3 L/min) for evening awakenings. morning double-blind placebo chronic asthma: a PEF. Percent of days with washout period randomized, The M group had a faster and exacerbations was decreased Arm 2 100 mcg/puff twice involving a subset of controlled trial. Ann larger initial response than the by 42% with M treatment vs. B + placebo tablet daily + placebo tablet patients (approximately Intern Med B group; 7–10 days after P (p <0.05) and by 63% with 40). 1999;130(6): 487– (n=251; initiation, effect of B treatment B treatment vs. P (p <0.05). 233 completers) 495. surpassed that of M. Days with asthma (Merck Research Arm 3 Placebo tablet + 22% of B group and 34% of exacerbations were less Laboratories) P placebo inhaler M group did not show frequent, and asthma-control improvement in FEV . days were more frequent in B (n=257; All patients used 1 vs. M treatment (p <0.05). 215 completers) salbutamol No difference was found (100 mcg/puff) as between B and M groups in needed. decrease in peripheral blood eosinophil count.

10 July 2007

11 July 2007

Study Characteristics Findings Duration of Active Treatment; Duration of Postintervention/ Citation Off-Treatment Exacerbations/ (Sponsor) Treatment Dose Followup Rescue Medication Use Lung Function Symptoms Adverse Events Bleecker et al. Low- Purpose/Objective: To provide comparative data on important Albuterol use was reduced by *Treatment with FP resulted in Greater improvement in mean Incidence of AE was similar between dose inhaled objective and subjective measures related to clinical efficacy of the 2.39 puffs/day for FP greater increase in FEV1 percentage of symptom-free groups, with 10% in each group having fluticasone lowest recommended dose of the ICS fluticasone propionate (FP) treatment vs. 1.45 puffs/day compared with Z (0.42 vs. 0.20 days for FP vs. Z treatment >1 drug-related AE. propionate versus compared with that of the recommended dose of oral zafirlukast (Z) for Z treatment (p <0.001), L, p <0.001), with differences (28.5 vs. 15.6, p <0.001), with Two patients in the zafirlukast group oral zafirlukast in the with differences in favor of FP in favor of FP by week 4. differences in favor of FP by had SAE resulting in withdrawal; no Arm 1 88 mcg twice daily 12 weeks after 8-to 14- treatment of by week 1. Differences occurred in favor week 1 patient in the FP group had SAE day run-in period persistent asthma. J Inhaled FP aerosol of FP in morning PEF (49.9 vs. Greater decrease in symptom resulting in withdrawal. Allergy Clin Immunol Albuterol as needed for Arm 2 20 mg twice daily 11.68 L/min, p <0.001) and score for FP vs. Z treatment 2000; 105(6 Pt 1): symptom relief evening PEF (38.9 vs. (–0.46 vs. –0.19, p <0.001), 1123-1129. Oral Z 10.5 L/min, p <0.001), with with differences in favor of FP (GlaxoWellcome, differences in favor of FP by after week 1 Inc.) week 2. FP increased the percentage of nights with no awakenings by 21.2% vs. 8.0% with Z (p <0.001). No difference occurred in exacerbations (p=0.19): 4% with FP and 6% with Z.

12 July 2007

Study Characteristics Findings Duration of Active Treatment; Duration of Postintervention/ Citation Off-Treatment Exacerbations/ (Sponsor) Treatment Dose Followup Rescue Medication Use Lung Function Symptoms Adverse Events Busse et al. (for the Purpose/Objective: To compare the efficacy and safety of low- FP treatment as compared to *FP treatment as compared FP treatment as compared to No difference was found in incidence Fluticasone dose fluticasone propionate (FP) and montelukast (M) as first-line M treatment resulted in to M resulted in greater M treatment resulted in of AE (71% of FP group vs. 68% of Propionate Clinical maintenance therapy in symptomatic patients by using short-acting greater decrease in rescue improvement in FEV1 greater improvement in M group); very few AE were drug- Research Study beta2-agonists alone to treat persistent asthma albuterol use (3.10 vs. 2.31 (0.51 vs. 0.33, p <0.001), in asthma symptom scores related. Group). Low-dose puffs/day, p <0.001) and FVC (0.42 vs. 0.29, p=0.002), (–0.85 vs. –0.60, p <0.001), No drug-related SAE occurred. Arm 1 88 mcg twice daily 24 weeks after fluticasone percentage of RFDs (45.9 vs. and in FEF25%–75% (0.66 vs. percentage of symptom-free propionate FP + placebo through metered- 8- to 14-day run-in 31.2, p <0.001). 0.41, p <0.001). days (32.0 vs. 18.4, compared with capsule dose inhaler + period p <0.001), and nighttime montelukast for first- (n=271; placebo capsule in Patients used inhaled awakenings/night (–0.64 vs. line treatment of 194 completers) evening albuterol as needed –0.48, p=0.023). persistent asthma: a throughout study. Physician assessment and randomized clinical Arm 2 10 mg in evening + patient satisfaction favored trial. J Allergy Clin Oral (M) + placebo 2 puffs of placebo FP over M treatment Immunol inhaler twice daily through (p <0.001). metered-dose inhaler 2001;107(3): (n=262; No difference was found in 461-468. 187 completers) exacerbations (4% of FP (GlaxoWellcome, group and 8% of M group). Inc.)

13 July 2007

Study Characteristics Findings Duration of Active Treatment; Duration of Postintervention/ Citation Off-Treatment Exacerbations/ (Sponsor) Treatment Dose Followup Rescue Medication Use Lung Function Symptoms Adverse Events Busse et al. Purpose/Objective: To assess the clinical benefits of an ICS and a FP treatment compared with *FP treatment improved FP treatment compared with Percentages of patients who Fluticasone leukotriene modifier as first-line treatment for persistent asthma in placebo improved pulmonary function more than placebo improved mean experienced AE were similar across propionate patients who were symptomatic when using short-acting percentages of albuterol-free Z treatment: 23.4% vs. 15.1% symptom scores (–0.65 vs. treatment groups (67%-72%), with compared with beta2-agonists alone days (48.9% vs. 19.0%) and for FEV1, –0.43), percentages of 12%–13% of AE in each group zafirlukast in albuterol use 46.7 L/min vs. 15.2 L/min for symptom-free days (28.8 vs. potentially related to study medication. controlling persistent Arm 1 88 mcg twice daily + 12 weeks after 8- to 14- (–2.8 vs. –1.3 puffs/day) morning PEF, and 6.9), and nighttime asthma: a Fluticasone placebo capsule day run-in period (p <0.006). 33.3 L/min vs. 12.8 L/min for awakenings, (–0.32 vs. –0.17) twice daily randomized double- propionate (FP) by Albuterol as needed for Z treatment compared with evening PEF (all p <0.05), with (all p <0.006). blind, placebo- inhaler + placebo symptom relief or placebo improved percentage improvements significantly FP compared with controlled trial. J capsule corticosteroids for of albuterol-free days (37.5% greater by day 4. Patients Z treatment improved mean Fam Pract (n=113) asthma exacerbations vs. 19.0%) and albuterol use treated with FP also improved symptom scores, percentage 2001;50(7): 595– were permitted during (–1.9 vs. –1.3 puffs/day). more than those treated with of symptom-free days, and 602. Arm 2 20 mg capsule twice the study. placebo (p <0.05). number of nighttime daily + 2 puffs of FP treatment compared with (GlaxoWellcome, Oral zafirlukast (Z) Z treatment improved the awakenings (p <0.04). Inc.) + placebo by placebo by inhaler twice daily percentage of albuterol-free Physician assessment of inhaler days and albuterol use efficacy and patients’ overall (n=111) (p <0.04). satisfaction favored FP over Z (p <0.025) or placebo Arm 3 Placebo capsule + 2 (p <0.001). Placebo capsule puffs of placebo by FP produced greater and placebo by inhaler twice daily improvement in asthma QoL inhaler scores compared with Z or (n=114) placebo (p <0.04). Most differences between FP and placebo were clinically meaningful; no differences between Z and placebo were clinically meaningful.

14 July 2007

Study Characteristics Findings Duration of Active Treatment; Duration of Postintervention/ Citation Off-Treatment Exacerbations/ (Sponsor) Treatment Dose Followup Rescue Medication Use Lung Function Symptoms Adverse Events Nathan et al. A Purpose/Objective: To compare the effects of low-dose fluticasone F treatment more than *After weeks 3 and 4, F treatment increased the No difference occurred in possible comparison of short- (F) and zafirlukast (Z) on measures of clinical efficacy and safety Z treatment reduced albuterol F treatment improved morning percentage of symptom-free drug-related AE (4% of the F group and term treatment with over 4 weeks; in addition, the effect of switching patients from Z to F use (–1.8 vs. PEF more compared to days compared to treatment 10% of the Z group). inhaled fluticasone therapy was evaluated –1.1 puffs/day, p=0.019). treatment with Z (p <0.033). with Z (19.8% vs. 11.6%, No SAE occurred. propionate and At endpoint, mean change in p=0.025). Arm 1 2 puffs of 44 mcg 4 weeks after 7- to 14- zafirlukast for morning PEF was greater in No difference in change morning and evening day screening period patients with Inhaled F the F group than in the Z group occurred in asthma symptom persistent asthma. (n=144; 139 A 4-week open-label (29.3 L/min, 8.2% change vs. scores (p=0.085). treatment period Am J Med completers) 18.3 L/min, 5.3% change; During the open-label period, followed. 2001;111(3): 195– p=0.022). no difference in change 202. Arm 2 20 mg morning and No other asthma No difference in change evening occurred in percentage of (GlaxoWellcome, Oral Z medications were occurred in evening PEF or symptom-free days. permitted during the Inc.) (n=150; 138 morning predose FEV1 During the double-blind study. completers) (p >0.20). period, no difference occurred During the open-label period, in percentage of patients with patients switched from Z to F exacerbations. had improvements in morning PEF (17.2 L/min), evening PEF (13.6 L/min), and FEV1 (0.11 L) (all p <0.001).

15 July 2007

16 July 2007

Brabson et al. Purpose/Objective: To compare the efficacy and safety of Albuterol use was reduced by *Mean changes in FEV1 were F treatment resulted in No SAE occurred in either group. At Efficacy and safety fluticasone (F) with zafirlukast (Z) in patients with persistent asthma 0.6 puff/day in patients 0.24 L in the F group and greater (p=0.001) least 1 AE potentially related to of low-dose who had been treated previously with low doses of ICS receiving F vs. an increase of 0.08 L in the Z group improvements in asthma treatment was experienced by 7% of fluticasone 0.1 puff/day in patients (p <0.001). symptom scores compared F group patients and by 4% of Z group Arm 1 44 mcg morning and 6 weeks after propionate receiving Z (p <0.001). F treatment increased morning with Z treatment patients (p=0.14). evening 8-day run-in period compared with F through metered- peak flow compared with (diff = –0.17 on 0–4 scale). zafirlukast in dose inhaler Z treatment (30 vs. 6 L/min, Fluticasone patients patients with (n=224; p <0.001). experienced more symptom- persistent asthma. 207 completers) free days (22 vs. 8, p <0.001). Am J Med Arm 2 20 mg Albuterol was used as Only 1% treated with F 2002;113(1): 15–21. experienced exacerbation vs. (GlaxoWellcome, Z as single tablet needed for symptom relief. 6% treated with Z (p=0.005). Inc.) (n=216; The completer rate was 171 completers) higher in the F group (92%) vs. the Z group (79%) (p <0.001). The percentage who withdrew due to lack of efficacy was higher in the Z group (13%) than in the F group (2%).

17 July 2007

Israel et al. Effects Purpose/Objective: To compare the effects of montelukast (M) and Both treatments reduced Improved FEV1 of the M group *Percentage overlap of days Laboratory AE occurred for 3.9% of the of montelukast and beclomethasone (BCD), as judged by days of asthma control average albuterol use (0.24 L) and BCD group of asthma control for M group, 3.0% of the BCD group, and beclomethasone on compared to placebo (0.38 L) differed from the treatments was 97.7%. 4.5% of the placebo group (p >0.05). airway function and Arm 1 10 mg tablet once 6 weeks following (p <0.001), with no difference placebo group (0.10 L, Means were 41.4% for M and asthma control. J Montelukast daily in evening 2-week single-blind between M p <0.001), with the effect of 41.1% for BCD (p=0.929) vs. Allergy Clin Immunol sodium (M) placebo baseline period (–30.3%) and BCD BCD greater than that of M 26.8% for placebo (p <0.001). 2002;110(6): (n=339; Inhaled albuterol for (–31.9%). (p <0.001). Fewer patients in the M group 847-854. 328 completers) symptomatic relief and The percentage of patients than in the placebo group had (Merck and Co., Inc., short-acting who used rescue an asthma attack (3% vs. Whitehouse Station, Arm 2 200 mcg (4 puffs) antihistamines were corticosteroids did not differ 8.1%, p <0.025), with no NJ; and USHH- BCD twice daily by permitted. Up to 2 uses between treatment groups difference between the Merck and Co., Inc., (n=332; inhalation of rescue oral (p=0.473). M was better than 2 treatments (3% vs. 3.9%). corticosteroid were West Point, PA) 318 completers) placebo (2.7% vs. 7.2%, No difference was found permitted. p=0.037), but BCD was not between treatment groups in Arm 3 (3.6% vs. 7.2%, p=0.127). percentage of days of Placebo sustained asthma control (n=111; (33.4% for M, 32.1% for 106 completers) BCD), with both greater than placebo (19.3%, p <0.05).

18 July 2007

Kanniess et al. Purpose/Objective: To compare montelukast (M) with low-dose Use of rescue medication *FEV1 increased (p <0.001) (Based on diary data of Montelukast versus fluticasone (F) decreased after both after F (0.50 L) and after M 38 patients) fluticasone: effects treatments (p <0.05), with no (0.37 L), with no difference F reduced daytime symptoms Arm 1 100 mcg twice daily Two 4-week periods on lung function, difference between between treatments. (1.5 to 0.8, p=0.05) compared with a 3- to 8-week airway F + placebo tablet treatments. PC of methacholine to baseline. washout interval after a 20 responsiveness and increased 1.33, doubling 1- to 2-week screening Neither treatment had an inflammation in concentrations after F period effect on nighttime symptoms moderate asthma. (p <0.001), but there was no (p >0.15). Eur Respir J Salbutamol was effect after M (p=0.39). 2002;20(4): 853– permitted as rescue Changes differed between 858. medication. drugs. (GlaxoSmithKline, Arm 2 10 mg at nighttime Percent of eosinophils Germany) M + placebo inhaler decreased after F by a factor of 2.7 (p <0.001), but not after M (p=0.16), with difference between groups. Level of nitric oxide decreased (p <0.01) after F, but not after M, with difference (p <0.001) between treatments.

19 July 2007

Baumgartner et al. Purpose/Objective: To compare the effectiveness of montelukast Percent reduction in Overlap in change in FEV1 *Overlap in percentage of AE were more frequent in the placebo Distribution of (M) and inhaled beclomethasone (B) in the treatment of adult beta-agonist use was greater between active treatment asthma control days between group (54%) than in the M (39%) and therapeutic patients (p <0.05) for patients taking B groups was 96%. No active treatment groups was B (42%) groups. response in asthma (45.7%) than for patients difference was found between 89%. The mean in the M A higher percentage of patients Arm 1 10 mg once daily 6 weeks after control between oral taking M (35.7%), with both change in M (12.1%) and B (50.7%) and B (57.9%) discontinued because of AE in the 2-week single-blind montelukast and Oral M greater than placebo (15.7%, (13.9%) groups, with both groups was greater than in placebo group (2.9%) compared with placebo run-in period inhaled (n=313; p <0.05). greater than the placebo group the placebo group (40.0%, the M (0%) and B (1%) groups. beclomethasone. 219 completers) Short-acting inhaled (6.4%, p <0.05). p <0.05). Difference favored Eur Respir J beta-agonist was used the B group over the M group 2003;21(1): 123– Arm 2 200 mcg (4 puffs) as needed throughout (diff 7.2, p <0.05). 128. Inhaled B twice daily study. Percent of patients with >1 (n=314; asthma attack did not differ 295 completers) between M (6%) and B (4%) groups; both groups had Arm 3 fewer attacks than the Placebo placebo group (15%, (n=103; p <0.05). 93 completers)

20 July 2007

21 July 2007

Study Characteristics Findings Duration of Active Treatment; Duration of Postintervention/ Citation Off-Treatment Exacerbations/ (Sponsor) Treatment Dose Followup Rescue Medication Use Lung Function Symptoms Adverse Events Ducharme. Inhaled Purpose/Objective: To compare the safety and efficacy of anti- Within 6 weeks, patients in Within 6 weeks, patients in the *Patients treated with LTRAs No difference occurred in the number of glucocorticoids leukotrienes and inhaled glucocorticoids as monotherapy in people the inhaled glucocorticoid inhaled glucocorticoid group were 60% more likely to patients who experienced any AE versus leukotriene with asthma group, compared to the anti- compare to the anti-leukotriene experience exacerbation (RR 1.0, 95% CI 0.9 to 1.1; 11 trials). receptor antagonists leukotriene group group experienced greater requiring systemic Arm 1 10 mg once daily Ranged from 4 to 37 as single agent experienced less rescue use improvement in FEV1 (WMD glucocorticoids than those (7 trials), weeks: asthma treatment: Anti-leukotrienes: of beta2-agonists 130 mL, 95% CI treated with inhaled systematic review of Montelukast 20 mg twice daily (4 4 weeks (2 trials), (–0.78, 95% CI –0.55 to 80 mL to 170 mL; 8 trials) and glucocorticoids (RR 1.6, 95% current evidence. (8 trials), zafirlukast trials), 6 weeks (4 trials), –1.00 puffs/day; 6 trials). morning PEF (WMD 19 L/min, CI 1.2 to 2.2; 11 trials). The BMJ (4 trials), or 5 mg once daily 12 weeks (3 trials), 95% CI 14 L to magnitude of effect was not 2003;326(7390): pranlukast (1 trial) (1 trial), 16 weeks (1 trial), 25 L; 7 trials). related to LTRA, inhaled 621–625. 450 mg once daily (1 24 weeks (2 trials), glucocorticoid preparation, or trial) 37 weeks (1 trial) baseline severity (all p >0.10). Arm 2 100 mg twice daily (4 Within 6 weeks, patients in ICS trials), the inhaled glucocorticoid vs. the anti-leukotriene group Beclomethasone 100 mg 3 times daily (1 trial), experienced fewer nocturnal dipropionate (BCD) awakenings per week (WMD (8 trials), 200 mg/day (1 trial), –0.56, 95% CI –0.28 to –0.77; fluticasone 5 trials) and fewer days with propionate 200 mg twice daily (4 trials), symptoms (–9%, 95% CI (5 trials), or –5% to –13%; 3 trials). budesonide (1 trial) 200–250 mg twice daily (1 trial), Anti-leukotriene was One trial used two associated with increased risk ICS arms. 400 mg/day (3 trials) of withdrawal due to poor asthma control (RR 2.5, 95% CI 1.8 to 3.5; 12 trials).

22 July 2007

23 July 2007

Study Characteristics Findings Duration of Active Treatment; Duration of Postintervention/ Citation Off-Treatment Exacerbations/ (Sponsor) Treatment Dose Followup Rescue Medication Use Lung Function Symptoms Adverse Events Jenkins et al. Purpose/Objective: To examine the relationship between clinical *Mean morning PEF was *Median nighttime symptom Five severe exacerbations occurred Traditional and and subjective variables in the assessment of response to treatment significantly higher with score was lower with (n=3 with montelukast; n=1 with patient-centered with 3 different classes of medication eformoterol (453 L/min) and eformoterol and with eformoterol; n=1 with washout after outcomes with three with fluticasone (468 L/min) fluticasone compared with eformoterol), and 11 moderate classes of asthma Arm 1 10 mg nocte 2-week run-in period; than with montelukast montelukast (p <0.001 and exacerbations occurred (n=8 with run- medication. Eur Encapsulated two 6-week treatment (428 L/min; both p <0.001). p=0.01, respectively). in, n=2 with eformoterol, n=1 with periods separated by 1- Respir J montelukast plus No difference was found No difference was found in fluticasone). week washout periods; 2005;26(1):36–44. placebo Turbuhaler between eformoterol and daytime symptom scores 6-week single-blind (Australian Federal fluticasone. between eformoterol and Arm 2 12 mcg b.i.d. fluticasone propionate Government, No difference in clinic FEV % fluticasone compared with 250 mcg b.i.d. plus 1 AstraZeneca, Eformoterol plus Reliever salbutamol pred. was found between montelukast (p=0.054 and placebo capsules Aventis Pharma, placebo capsule was permitted montelukast and eformoterol, p=0.06, respectively). throughout the study. GlaxoSmithKline, with the effect of fluticasone Better asthma control Merck Sharp and better than both. occurred with both Dohme, New South Fluticasone >eformoterol for eformoterol and fluticasone Wales State lung function factor derived than with montelukast. Department of from PCA. Mean absolute improvement Health) in QoL scores with eformoterol and fluticasone was not clinically important. Eformoterol >fluticasone for symptom/relievers use factor and equivalent for patient- centered factor derived from PCA.

24 July 2007

Straub et al. The Purpose/Objective: To investigate the therapeutic effect of Mean FEV0.5 improved in the Median score in the M group effect of montelukast montelukast (M) in a well-defined group of very young children with M group (189.0 to 214.4 mL; improved from 5.5 to 1.5 on lung function and recurrent wheeze and a positive family history of asthma and allergy p=0.038) but not in the placebo (p=0.04) but not in the exhaled nitric oxide group (161.0 to 166.6 mL, placebo group (3.0 to 4.0, in infants with early Arm 1 4 mg daily 4 weeks p=0.026). p=0.35). childhood asthma. M Fractional exhaled nitric oxide Eur Respir J (n=12) decreased in the M group 2005;25(2): (29.8 to 19.0 ppb, p=0.01), but 289-294. Arm 2 1 placebo tablet daily not in the placebo group (33.4 Placebo to 34.5 ppb, p=0.25). (n=12) Difference in change between the groups was significant (p=0.04).

Garcia-Garcia et al. Purpose/Objective: To compare the efficacy of orally administered Percentage of days with Percentage of predicted FEV1 *Percentage of RFDs was No difference in AE (4.4% of the Montelukast, montelukast (M) with that of inhaled fluticasone (F) in the percentage beta-receptor agonist use increased from 88.1% to 89% 84% in the M group and M group and 3.2% of the F group) compared with of asthma RFDs among 6- to 14-yr-old patients with mild persistent was 15.4% in the M group in the M group and from 88.9% 86.7% in the F group, change occurred. fluticasone, for asthma and 12.8% in the F group to 91.7% in the F group; from baseline was 22.4% vs. No SAE occurred in either group. control of asthma (p=0.003), a decrease of difference of 2.2% in favor of 25.2%, a difference of among 6- to Arm 1 5 mg tablet once at 12 months after 4-week 22.7% in the M group and fluticasone (p=0.004). <1 day/month and above the 14-year-old patients M plus placebo bedtime (10 mg if run-in period 25.4% in the F group. noninferiority limit. patient turned 15 with mild asthma: inhaler The percentage of patients The percentage with asthma during study) the MOSAIC study. (n=495; n=459 with additional asthma rescue attack was 32.2% in the Pediatrics completers) medication was 20.7% in the M group vs. 25.6% in the 2005;116(2): 360– M group vs. 13.5% in the F F group (RR = 1.26, 95% CI 369. Arm 2 2 puffs of 50 mcg group (RR = 1.56, 95% CI 1.04 to 1.53). morning and evening (Merck and Co.) Fl plus placebo 1.17 to 2.06). Mean asthma-related tablet All patients received QoL score increased from (n=499; n=466 open-label salbuterol 5.4 to 6.3 in the M group and completers) inhaler to be used as from 5.3 to 6.4 in the F group needed. (p=0.036).

25 July 2007

Study Characteristics Findings Duration of Active Treatment; Duration of Postintervention/ Citation Off-Treatment Exacerbations/ (Sponsor) Treatment Dose Followup Rescue Medication Use Lung Function Symptoms Adverse Events Ostrom et al. Purpose/Objective: To evaluate efficacy, safety, health outcomes, FP vs. M treatment *FP vs. M treatment resulted FP vs. M treatment resulted in Incidence of drug-related AE was Comparative and cost-effectiveness of treatment with fluticasone propionate (FP) decreased mean total in greater increase in mean greater decrease in nighttime similar in FP (7%) and M (6%) efficacy and safety versus montelukast (M) in children with persistent asthma albuterol use (–1.43 vs. percent FEV1 (10.62 vs. 4.60; asthma symptom scores treatment. of low-dose –1.23, p=0.018) and mean p=0.002), morning PEF (39.9 (–0.40 vs. –0.19; p <.001) No SAE occurred in FP group; 1 in the Arm 1 50 mcg twice daily 12 weeks after 8- to 14- fluticasone nighttime albuterol use vs. 23.0; p=0.004), and and with no difference for M group required non-drug-related through multidose day run-in period propionate and FP + placebo (–0.39 vs. –0.21, p <0.001) evening PEF (35.5 vs. 20.4; daytime asthma symptom hospitalization. montelukast in capsule powder inhaler + but not mean daytime p=0.020). score (–0.891 vs. –0.75, placebo capsule Drug-related withdrawals occurred in children with (n=172; albuterol use Results were consistent when p=0.20) or percentage of once daily 2 patients in the FP group and 1 patient persistent asthma. J 150 completers) (–1.01 vs. –0.92, p=0.10). analyzed for each of 2 severity symptom-free days (37.7 vs. in the M group. Pediatr 2005;147(2): FP vs. M treatment increased groups separately. 31.3; p=0.087). 213-220. Arm 2 5 mg once daily + Patients used inhaled percentage of RFDs (45.1 vs. Mean daily total asthma- (GlaxoSmithKline, Oral M + placebo placebo inhaler twice albuterol as needed 35.0; p=0.002). related cost/patient in Inc.) inhaler daily throughout the study. FP treatment was one-third (n=172; that of M treatment ($1.25 vs. 134 completers) $3.49). Mean total asthma- related daily cost per successfully treated patient (achieving >15% FEV1 improvement) was $4.03 for FP and $17.45 for M.

26 July 2007

Study Characteristics Findings Duration of Active Treatment; Duration of Postintervention/ Citation Off-Treatment Exacerbations/ (Sponsor) Treatment Dose Followup Rescue Medication Use Lung Function Symptoms Adverse Events Szefler et al. Purpose/Objective: To examine the variability of response to ICSs Agreement in responses to Characterization of and LTRAs in children with asthma to identify patient features that 2 medications at end of within-subject would serve as indicators for selection of the medication most likely 8-week periods; concordance responses to to achieve a favorable response in individual patients correlation of 0.55 (95% CI fluticasone and 0.43 to 0.65; n=126) Arm 1 100 mcg per Two 8-week periods montelukast in *Mean FEV improvement was inhalation; after a 5- to 10-day 1 childhood asthma. J Fluticasone 6.8% for FP and 1.9% for 1 inhalation twice characterization period Allergy Clin Immunol propionate + M treatment groups (mean diff. daily 2005;115(2): 233– placebo tablet (FP) 4.9%, p <0.001). 242. Arm 2 1 tablet at night; First 4 weeks of 2nd Defining response as FEV1 (National Heart, 5 mg for those 6–14 treatment period were >7.5%, 17% responded to both Lung, and Blood Montelukast + placebo inhaler (M) yr of age and 10 mg considered sufficient for FP and M; 23% responded to Institute) FP only; 5% responded to M Study n=144; for those 15–18 yr of washout of medication age used in first period. only; and 55% responded to 127 completers neither. Difference in response (FP – M) was associated with lower prebronchodilator FEV1 % predicted and FEV1/FVC ratio, lower methacholine PC20 value, higher bronchodilator use, higher FEV1 response to bronchodilator, higher exhaled nitric oxide level, higher ECP level, and nonminority race. Multivariable regression model for difference in response (FP – M) included baseline prebronchodilator FEV1/FVC ratio, baseline log2 ECP value, body mass index, and log2 PC20 value.

27 July 2007

Study Characteristics Findings Duration of Active Treatment; Duration of Postintervention/ Citation Off-Treatment Exacerbations/ (Sponsor) Treatment Dose Followup Rescue Medication Use Lung Function Symptoms Adverse Events Zeiger et al. Short- Purpose/Objective: To determine whether montelukast is as *M was as effective treatment During the 12-week double- During the 12-week double- term and long-term effective as fluticasone (F) in controlling mild persistent asthma, as as F with respect to mean blind period, the F group had blind period, no difference asthma control in determined by RFDs percentage of RFDs during increase in FEV1 (2.6%, 95% was found between F and patients with mild the 12-week double-blind CI 1.2 to 3.9) vs. the M group M groups in change in persistent asthma Arm 1 2 puffs of 44 mcg 12-week double-blind period. Mean percentage of (–0.3%, 95% CI –1.6 to 1.0), asthma symptoms score receiving Inhaled F twice daily + placebo period and 36-week asthma RFDs days was with mean difference of 2.9% (p=0.08), asthma control montelukast or (n=191; 173 tablet open-label period (10% 74.9% for F group and 73.1% (94% CI 1.3 to 4.4, p <0.001). score (p=0.09), or asthma- fluticasone: a completed double- of participants switched for M group (diff. 1.8%, 95% No difference between F and specific QoL score (p=0.20). randomized blind therapy; 177 therapies to preserve CI –3.2% to 6.8%; M groups occurred in morning During the open-label period, controlled trial. Am J entered open-label masking in preceding 0.5 days/month). PEF or total eosinophil counts. F vs. M treatment group Med 2005; period; period); 3-week placebo During double-blind period, showed improved asthma 118(6):649–657. 151 completers) run-in period those in lowest quartile of symptom score (diff. –2.09, (Merck & Co., Inc.) FEV1 (<86%) had more RFDs 95% CI –3.2 to 0.8, p=0.002), Arm 2 10 mg once nightly + with F than with M treatment. with no difference in change placebo inhaler Montelukast (M) During open-label period, in control score (diff. –0.1, (n=189; 177 mean percentage of RFDs 95% CI –0.2 to 0.1) or completed double- was greater for F group vs. asthma-specific QoL score blind therapy; 173 M group (77.3% vs. 71.1%; (diff 0.1, 95% CI –0.0 to 0.3, entered open-label diff 6.2%, 95% CI 0.8% to p=0.11). period; 11.7%). 138 completers) Those in the highest quartile of days of albuterol use at baseline (5–6 days/week) had more RFDs with F than with M during the open-label period, whereas those in the lower 3 quartiles (<4 days/week) F and M groups were comparable over the 48-week study. No difference was found between F and M groups in increase in morning PEF during either period.

28 July 2007

Study Characteristics Findings Duration of Active Treatment; Duration of Postintervention/ Citation Off-Treatment Exacerbations/ (Sponsor) Treatment Dose Followup Rescue Medication Use Lung Function Symptoms Adverse Events Zeiger et al. Purpose/Objective: To determine intraindividual and interindividual Greater improvement occurred Asthma control days were Response profiles to response profiles and predictors of response to an ICS and an LTRA after FP vs. M treatment in increased by both FP fluticasone and prebronchodilator FEV1/FVC (2.8 days/week) and M montelukast in mild- Arm 1 100 mcg/ inhalation; 5–10 day run-in period; (82.2 vs. 79.0, p <0.0001), (2.1 days/week) treatment, to-moderate Fluticasone 1 inhalation twice 16-week trial, with two FEV variability (7.5 vs. 8.5, with a concordance persistent childhood propionate (FP) daily 8-week treatment p=0.03), morning PEF (334.2 correlation of 0.70 (95% CI asthma. J Allergy periods vs. 324.8, p=0.0002), R5 (0.60 0.60 to 0.78) and difference Clin Immunol 2006; Arm 2 1 tablet at night; First 4 weeks of second vs. 0.63, p=0.003), and area of between FP and M 117(1):45–-52. Montelukast (M) 5 mg for those 6–12 treatment period was reactance (1.25 vs. 1.53, (p <0.001). yr of age and 10 mg (National Heart, (n=127 completed washout period for the p=0.0003). 29.3% achieved >1 more Lung, and Blood both arms of for those 1st treatment. 15–18 yr of age Decrease occurred in exhaled day/week with FP vs. Institute) treatment) Subjects received an nitric oxide after both FP and M treatment; 12.2% achieved active drug and a M treatment (20.6 and 30.9, >1 more day/week with M vs. matching placebo for p <0.001), with the decrease FP treatment. the alternative drug. greater after FP (p=0.0028). Both FP and M treatment Higher exhaled nitric oxide increased Asthma Control levels at baseline Questionnaire scores discriminated asthma control (0.59 and 0.76, p <0.001), day response to treatments, favoring FP (p=0.009). with greater responses to FP than to M treatment (p=0.011).