Episode-free Days Research Articles

Intermittent Tiotropium Bromide for Episodic Wheezing: A Randomized Trial.

Options to treat and prevent episodic wheezing in children are scarce. Our objective was to assess the efficacy of intermittent tiotropium bromide treatment in early childhood episodic wheezing. This 48-week, randomized, open-label, controlled, parallel-group trial was conducted at 4 hospitals in Finland. Children aged 6 to 35 months with 2 to 4 physician-confirmed episodes of wheeze and/or shortness of breath were considered eligible. Study participants were randomly allocated to receive 1 of 3 treatments: once-daily tiotropium bromide 5 µg for 7 to 14 days during respiratory tract infections and as-needed albuterol sulfate 0.2 mg (n = 27), twice-daily fluticasone propionate 125 µg for 7 to 14 days during respiratory tract infections and as-needed albuterol sulfate 0.2 mg (n = 25), or as-needed albuterol sulfate 0.2 mg alone (n = 28). The primary outcome was efficacy, assessed as intention-to-treat by comparing the proportion of episode-free days (the days lacking symptoms or treatments) between the treatment groups. The proportion of episode-free days was higher in those receiving intermittent tiotropium bromide (median 97% [interquartile range, 93% to 99%]) than in those receiving intermittent fluticasone propionate (87% [78% to 93%], P = .002), or with as-needed albuterol sulfate alone (88% [79% to 95%], P = .003). Adjustment with allergic sensitization, the baseline number of physician-confirmed episodes of wheeze and/or shortness of breath, or short-course glucocorticoid treatment in the 2 weeks before the enrollment, did not affect the result. Intervention-related adverse events were not seen. Intermittent tiotropium bromide treatment may be an effective alternative to current therapies for episodic wheezing. Before implementation of use, further research on safety and efficacy is indicated.

Comparing the efficacy of Budesonide and Montelukast in children with asthma: a prospective interventional open label controlled clinical study

Background: Bronchial asthma is a chronic inflammatory airway disease and is more prevalent in children. Inhaled corticosteroids (Budesonide) and leukotriene receptor antagonist (Montelukast) are the drugs of choice for asthma in children. The present study was aimed to compare the efficacy of these drugs in childhood asthma at tertiary care center.Methods: This is a prospective interventional open label controlled clinical study carried out from January 2012 to December 2014. Children recently diagnosed with mild persistent asthma that attended Asthma clinic or admitted in ward of department of paediatrics LTMMC and Hospital, Sion, Mumbai was participated in the study. A total of 70 patients were selected for the study and are categorized into two groups consisting of 35 in each group. Group A patients were given metered dose inhaler (MDI) Budesonide 200 mcg 1 puff twice a day (with MDI spacer and mask for children <5 years and without mask for children >5 years. Group B patients were given Montelukast 4 mg (<5 years) and 5 mg (>5 years) tablet as once a daily in the evening for 1 year. Primary and secondary outcome measures were calculated and analysed.Results: No significant difference on the basis of age and gender was observed among both groups. The complaints of cough, wheeze and breathlessness, lesser emergency department visits, nebulization and lesser number of systemic steroids (days/year) was significantly lesser in patients of group A (p<0.05) compared to group B. Group A subjects had lesser number of acute exacerbations, required lesser number of systemic steroids courses and the frequency of hospitalization. Statistically significant (p<0.05) difference was observed in episode free days in a year among both groups.Conclusions: The findings of the study prove that Budesonide had better efficacy over Montelukast in control of asthma.

Analysis of 2-Week Data from Two Randomized, Controlled Trials Conducted in Subjects with Frequent Heartburn Treated with Esomeprazole 20 mg

PurposeThese secondary analyses used data from 2 similarly designed studies in subjects experiencing frequent heartburn to evaluate the efficacy of esomeprazole 20 mg once daily for 2 weeks, which reflects the approved over-the-counter dosage and duration. MethodsSubjects without endoscopically identified erosive esophagitis who were experiencing heartburn for ≥6 months and ≥4 of 7 days prior to baseline (study 1, N = 368; study 2, N = 349) were randomly assigned to receive double-blind treatment with esomeprazole 40 or 20 mg (administered as esomeprazole magnesium trihydrate 44.5 and 22.3 mg, respectively) or placebo once daily for 4 weeks. Subjects recorded the severity of heartburn in a daily diary, and investigators assessed subjects at each study visit. Two-week assessments were the primary end points of interest in these analyses and included the percentage of subjects with complete heartburn resolution (no episodes during 7 consecutive days), time to sustained complete heartburn resolution (the first of 7 consecutive episode-free days), and heartburn relief (no episodes other than ≤1 mild episode during 7 consecutive days). FindingsAt week 2, the percentages of subjects who experienced complete heartburn resolution were significantly greater with esomeprazole 40 mg (study 1, 26.1%; study 2, 35.3%) and 20 mg (study 1, 25.2%; study 2, 35.7%) compared with placebo (study 1, 9.0%; study 2, 3.4%) (all, P ≤ 0.001). Beginning on day 1, the percentages of subjects who experienced sustained heartburn resolution was significantly greater in the groups treated with esomeprazole 40 mg (study 1, 19%; study 2, 19%; P < 0.0001) and 20 mg (study 1, 10%; study 2, 15%; P < 0.05) compared with the group that received placebo (study 1, 2%; study 2, 1%). Additionally, at week 2, the percentages of subjects experiencing heartburn relief were significantly greater with esomeprazole 40 mg (study 1, 35.3%; study 2, 40.5%) and 20 mg (study 1, 34.5%; study 2, 46.4%) compared with placebo (study 1, 16.5%; study 2, 8.6%) (all, P ≤ 0.001). ImplicationsThe results of this study demonstrate that once-daily treatment with esomeprazole 20 mg for 2 weeks effectively resolved subjects׳ heartburn compared with placebo, beginning on day 1. Studies precede FDA Act 801 clinical trial registration and results submission requirements.

Three decades of recurrent manic episodes modulated by nineteen years of lithium therapy

Investigations of mania without depression are limited. This study is based on a 34‐year record by one of the authors (nlc) who first experienced a manic episode in 1978 at the age of 36. Lithium therapy was begun in the midst of an episode seven years later, continued for 19 years, then discontinued. Overall, without depression, there were 102 manic episodes with a mean duration of 18 days per episode. Episodes before (Period I), during (Period II), and after (Period III) lithium therapy were compared. In Period I (7 yrs) there were 12.7 episodes with a mean frequency of 1.8 episodes per year and a mean duration of 17 days per episode. In Period II (19 yrs) there were 63.3 episodes with a mean frequency of 3.4 episodes per year and a mean duration of 14 days per episode. In Period III (9 yrs) there were 26.0 episodes with a mean frequency of 3.0 episodes per year and a mean duration of 28 days per episode. Overall, 85% of the days were episode‐free during the 34‐year period of recurrent manic episodes. In Periods I, II and III, 92%, 87% and 77%, respectively, of the days were episode‐free. This demonstrates that episode‐free days were not increased during or after 19 years of lithium therapy.

Episodic Use of an Inhaled Corticosteroid or Leukotriene Receptor Antagonist in Preschool Children With Moderate-To-Severe Intermittent Wheezing

Bacharier LB, Phillips BR, Zeiger RS, et al. J Allergy Clin Immunol. 2008;122(6):1127–1135PURPOSE OF THE STUDY. To examine the effectiveness of episodic use of an inhaled corticosteroid (ICS) or leukotriene receptor antagonist (LTRA) in preschool-aged children with moderate-to-severe intermittent wheezing associated with respiratory tract illness (RTI).STUDY POPULATION. Children 12 to 59 months of age with ≥2 episodes of wheezing with RTI in the previous year and either 2 urgent care visits for wheezing, 2 wheezing episodes requiring oral steroid treatment (<6 courses), or 1 episode requiring urgent care and oral steroid treatment.METHODS. The study design was a randomized, double-blind, placebo-controlled trial, with children assigned randomly to 1 of 3 treatment groups with instructions to treat for 7 days at the onset of each RTI-associated symptom set during a 12-month period: (1) budesonide suspension (1 mg twice daily) plus LTRA placebo, (2) montelukast (4 mg daily) plus ICS placebo, or (3) ICS placebo plus LTRA placebo. All groups received albuterol 4 times per day for the first 48 hours of illness plus as-needed dosing. Orally administered steroids were available if needed, but other asthma medications were prohibited. Symptom/treatment diaries were maintained, and clinic/telephone follow-up evaluations were conducted. The primary outcome was the proportion of episode-free days (EFDs). Secondary outcomes included severity of lower respiratory tract symptoms in the 14-day period after initiation of treatment, time to initiation and number of orally administered steroids, number of wheezing episodes, days missed from day care and work, caregiver quality of life, unscheduled visits because of acute wheezing, and linear growth.RESULTS. Two hundred thirty-eight children were randomly assigned and were well matched with respect to baseline characteristics. Adherence to therapy was similar between the groups. EFDs did not differ among the 3 treatment groups (adjusted EFD mean: budesonide: 76%; montelukast: 73%; placebo: 74%). Relative to placebo, there were significant reductions in trouble breathing (budesonide: 37.5%; montelukast: 36.8%; P = .003) and interference with activity (budesonide: 31.9%; P = .01; montelukast: 39.6%; P = .001). Wheezing scores were reduced with montelukast (33.5%; P = .02) but not with budesonide (24.6%; P = .09). Overall, total symptom scores were reduced with montelukast (29.6%; P = .006) and budesonide (24.6%; P = .02). Among participants with positive asthma predictive index status, both budesonide and montelukast significantly reduced scores for trouble breathing (budesonide: 48.0%; P = .001; montelukast: 40.3%; P = .007) and activity interference (budesonide: 43.6%; montelukast: 53.7%; P < .001); only montelukast reduced wheezing (P = .049). Similar findings were seen for children with previous oral steroid therapy use.CONCLUSIONS. For preschool-aged children with moderate-to-severe intermittent wheezing, episodic use of either budesonide or montelukast early in RTIs did not increase the proportion of EFDs. However episodic use of an ICS or LTRA decreased symptom burden, particularly for those with risk factors for asthma or greater illness severity (use of oral corticosteroid therapy).REVIEWERS COMMENTS. This study was conducted to address an important clinical question: is the episodic use of an ICS or LTRA effective in decreasing the morbidity associated with severe intermittent wheezing in preschool-aged children? Using a unique study design, the authors demonstrated benefit for children with symptoms and treatment predictive of asthma, indicating consideration for the early use of antiinflammatory medications. Additional study is needed to address this important question fully.

Patient characteristics associated with improved outcomes with use of an inhaled corticosteroid in preschool children at risk for asthma

Maintenance inhaled corticosteroid (ICS) therapy in preschool children with recurrent wheezing at high-risk for development of asthma produces multiple clinical benefits. However, determination of baseline features associated with ICS responsiveness may identify children most likely to benefit from ICS treatment. To determine if demographic and atopic features predict response to ICS in preschool children at high risk for asthma. Two years of treatment with an ICS, fluticasone propionate (88 microg twice daily), was compared with matching placebo in a double-masked, randomized, multicenter study of 285 children 2 and 3 years old at high risk for asthma development. Baseline demographic and atopic features were related to clinical outcomes in a post hoc subgroup analysis. Multivariate analysis demonstrated significantly greater improvement with fluticasone than placebo in terms of episode-free days among boys, white subjects, participants with an emergency department (ED) visit or hospitalization within the past year, and those who experienced more symptomatic days at baseline. Children with aeroallergen sensitization experienced greater benefits in terms of oral corticosteroid use, urgent care and ED visits, and use of supplemental controller medications. More favorable responses to ICS than placebo in high-risk preschool children over a 2-year period were more likely in those with a ED visit or hospitalization for asthma within the past year, children with aeroallergen sensitization, boys, and white subjects.

Episodic use of an inhaled corticosteroid or leukotriene receptor antagonist in preschool children with moderate-to-severe intermittent wheezing

Acute wheezing illnesses in preschoolers require better management strategies to reduce morbidity. We sought to examine the effectiveness of episodic use of an inhaled corticosteroid and a leukotriene receptor antagonist in preschoolers with intermittent wheezing. In a randomized, double-blind, placebo-controlled 12-month trial, 238 children aged 12 to 59 months with moderate-to-severe intermittent wheezing received 7 days of either budesonide inhalation suspension (1 mg twice daily), montelukast (4 mg daily), or placebo in addition to albuterol with each identified respiratory tract illness (RTI). Proportion of episode-free days (EFDs) during the 12-month trial was the primary outcome. The 3 treatment groups did not differ in proportions of EFDs, with adjusted mean EFDs of 76% (95% CI, 70% to 81%) for budesonide, 73% (95% CI, 66% to 79%) for montelukast, and 74% (95% CI, 65% to 81%) for conventional therapy (P = .66). The 3 groups did not differ in oral corticosteroid use, health care use, quality of life, or linear growth. However, during RTIs, budesonide and montelukast therapy led to modest reductions in trouble breathing (38% [P = .003] and 37% [P = .003], respectively) and interference with activity scores (32% [P = .01] and 40% [P = .001], respectively) that were most evident in those with positive asthma predictive indices. In preschool children with moderate-to-severe intermittent wheezing, episodic use of either budesonide or montelukast early in RTIs, when added to albuterol, did not increase the proportion of EFDs or decrease oral corticosteroid use over a 12-month period. However, indicators of severity of acute illnesses were reduced, particularly in children with positive asthma predictive indices.

Long-term Inhaled Corticosteroids in Preschool Children at High Risk for Asthma

Guilbert TW, Morgan WJ, Zeiger RS, et al. N Engl J Med. 2006;354:1985–1997 PURPOSE OF THE STUDY. To determine the role of inhaled corticosteroid (ICS) in preventing the development of asthma in a group of high-risk children before the development of symptomatic disease or abnormal lung function. STUDY POPULATION. Subjects were 285 children aged 2 to 3 years at high risk for developing asthma. METHODS. Subjects were assigned to fluticasone propionate (FP) 88 μg twice per day with a pressurized metered-dose inhaler with spacer or placebo for a 2-year treatment period. The patients were observed without treatment for 1 year. RESULTS. During the 2-year treatment period, there was significant improvement in symptom-free days for those in the FP group (86.8%–85.9%). Children in the FP group had more episode-free days, decreased exacerbations, and decreased need for extra controller medication. Those in the ICS group had a 1.1-cm decrement in growth after the first 2 years of the study, but this difference decreased to 0.7 cm after the 1-year observation period. CONCLUSIONS. Although ICS had a significant effect on the burden of asthma during the treatment period, there was no evidence that a long-term effect was carried over to the 1-year observation period. REVIEWER COMMENTS. The burden of childhood asthma is benefited with administration of ICS, but there is no evidence that long-term disease modification occurs.

What do parents want from their child's asthma treatment?

Nearly 5 million children in the United States are affected by asthma, which is more than 5% of the population younger than 18 years. In children four years or younger, the prevalence increased 160% from 1980 to 1994. There are several effective drugs that relieve the symptoms of asthma and others are currently being developed, but even when these medications are prescribed, they may be underutilized because parents fear the possibility of adverse events. Up to now there is no knowledge which are the main drivers of caregiver's preferences for a safe and effective medication for preschool children in general. The study population was caregivers with children aged 4 years or below. Sample size was 42; results were checked by Monte Carlo simulation. FOR A CONJOINT ANALYSIS A STATUS QUO TREATMENT AND HYPOTHETICAL TREATMENT OPTIONS WERE DEFINED BY FOUR ATTRIBUTES: Episode-free days, risk of exacerbation, information available for the long-term impact of the treatment, and out-of-pocket expenses. It was possible to use the status quo as the reference scenario, permitting to couch this ranking in terms of a decision to purchase the product. Relative importances for each product attribute as well as utility estimations for each attribute level were calculated. The overall result was that the most important feature for an asthma treatment, in this study, was the attribute of episode-free days. On a scale from 0 to 100 this attribute got the calculated relative importance of 44.2. In contrast to this finding is the relative importance of the attribute EXACERBATION, which only reached 16.2, which is the most unimportant attribute of the attributes offered. Even the variable INFORMATION available on long-term effects in children between 4 years and 14 years of age was more important than the side effects (19.2). Out-of-pocket expenses per month were the second most (relative) important attribute (20.5).

Willingness-to-pay for caregivers of children with asthma or wheezing conditions

Nearly 5 million children in the United States are affected by asthma, which is more than 5% of the population younger than 18 years. In children four years or younger, the prevalence increased 160% from 1980 to 1994. There are several effective drugs that relieve the symptoms of asthma and others are currently being developed, but even when these medications are prescribed, they may be underutilized because parents fear the possibility of adverse events. There is no knowledge whether caregivers would be willing to pay (WTP) for safe and effective medications in general. IN A CONJOINT ANALYSIS, THE STATUS QUO AND HYPOTHETICAL TREATMENT OPTIONS ARE DEFINED BY FOUR ATTRIBUTES: episode-free days, risk of exacerbation, information available on the long-term impact of the treatment, and out-of-pocket expenses. Based on random utility theory, a binary purchase decision equation is specified and estimated using probit. Several tests were performed with regards to the scaling of the attribute variables, the linearity of the utility function used, and the derivation of a final model. Marginal willingness-to-pay per month for 20 additional episode-free days due to a new treatment turns out to be US$6.00. An interesting question from the (industry) policy point of view for possible new products is the amount of WTP for the product as a whole. Assuming that the final model is correctly specified, the (negative) constant may be interpreted as indicating that caregivers feel confident with the asthma treatment options already on the market and having hence not a positive relation to a new treatment.

Forced Expiratory Volume in 1 Second Percentage Improves the Classification of Severity Among Children With Asthma

Spirometry is an important component of the National Asthma Education and Prevention Program guidelines for asthma, yet published data show variable associations between forced expiratory volume in 1 second percentage (FEV1%) predicted, symptoms and health care utilization. The objective of this analysis was to examine the association between FEV1% and future risk of exacerbations among a well-characterized population of children with asthma. Using data that are available from the Childhood Asthma Management Program, we examined the relationship between prebronchodilator FEV1% and important clinical outcomes. Multiple observations of FEV1 were available for each patient; multivariate regression analysis, using a general estimating equation approach, was used to control for the correlation between repeated measurements among individuals and potential confounders. FEV1% was categorized into 4 levels and as a continuous variable. Outcomes of interest included mean symptom score (0-3), episode-free days, and asthma-related events (oral steroid use, emergency department visits, and hospitalizations) during the ensuing 4-month period. Our analysis was limited to the placebo group (N = 417). We observed a clear relationship between prebronchodilator FEV1% and important clinical outcomes. In multivariable models that simultaneously controlled for covariates of interest, age at baseline, time, previous event history, and nocturnal awakenings, a significant relationship between FEV1% and asthma symptoms and serious asthma exacerbations (oral steroids, emergency department visits, and hospitalizations) was observed. Compared with children with an FEV1% > or = 100%, children with FEV1% 80% to 99%, 60% to 79%, and < 60% were 1.3, 1.8, and 4.8, respectively, more likely to have a serious asthma exacerbation during the ensuing 4 months. CONCLUSIONS. In children with mild to moderate asthma, FEV1% predicted is independently associated with future asthma symptoms and health care utilization. Previous asthma-related hospitalizations and nocturnal symptoms also were independently associated with risk for future adverse events. FEV1 is an important component of asthma health status and asthma severity classification.

Long-Term Inhaled Corticosteroids in Preschool Children at High Risk for Asthma

It is unknown whether inhaled corticosteroids can modify the subsequent development of asthma in preschool children at high risk for asthma. We randomly assigned 285 participants two or three years of age with a positive asthma predictive index to treatment with fluticasone propionate (at a dose of 88 mug twice daily) or masked placebo for two years, followed by a one-year period without study medication. The primary outcome was the proportion of episode-free days during the observation year. During the observation year, no significant differences were seen between the two groups in the proportion of episode-free days, the number of exacerbations, or lung function. During the treatment period, as compared with placebo use, use of the inhaled corticosteroid was associated with a greater proportion of episode-free days (P=0.006) and a lower rate of exacerbations (P<0.001) and of supplementary use of controller medication (P<0.001). In the inhaled-corticosteroid group, as compared with the placebo group, the mean increase in height was 1.1 cm less at 24 months (P<0.001), but by the end of the trial, the height increase was 0.7 cm less (P=0.008). During treatment, the inhaled corticosteroid reduced symptoms and exacerbations but slowed growth, albeit temporarily and not progressively. In preschool children at high risk for asthma, two years of inhaled-corticosteroid therapy did not change the development of asthma symptoms or lung function during a third, treatment-free year. These findings do not provide support for a subsequent disease-modifying effect of inhaled corticosteroids after the treatment is discontinued. (ClinicalTrials.gov number, NCT00272441.).

Single-Inhaler Combination Therapy for Asthma

Clinical studies have shown that the combination of an inhaled corticosteroid (ICS) and a long-acting beta(2)-adrenoceptor agonist (LABA) for patients with asthma is more effective than the use of ICS alone in equivalent or higher doses, as well as the use of other combinations. However, the relatively higher acquisition costs for the combination therapy require assessment of the value of the incremental costs, especially from a societal perspective. This review provides an overall assessment of the cost effectiveness of ICS plus LABA combination therapy for asthma. A systematic literature research was conducted in MEDLINE to identify studies published between January 1994 and September 2005. Cost-effectiveness studies derived from 11 clinical studies were identified. The ICS plus LABA combination was compared with ICS alone in eight studies, ICS plus a leukotriene antagonist in two studies, and a leukotriene antagonist alone in one study. All studies focused on measuring direct medical costs in a total of six different healthcare systems, and three studies conducted sensitivity analyses, including productivity costs. Outcomes were measured in treatment success (changes in lung function), episode-free days, and symptom-free days by evaluating short-term follow-up. The combination of ICS and LABA was found to be more efficacious and cost effective compared with ICS alone or alternative combinations of controller medications. Further considerations for measuring long-term outcomes and dose-response relationships might be required to provide further evidence on the cost effectiveness of combination therapy with ICS plus LABA.

Cost-effectiveness analysis of budesonide/formoterol compared with fluticasone in moderate-persistent asthma

In this economic evaluation, conducted alongside a randomized, double-blind clinical trial, economic data were collected from 339 patients with moderate-persistent asthma randomized to receive twice-daily, double-blind treatment with budesonide/formoterol 160/4.5 microg in a single inhaler (n=166) or fluticasone propionate 250 microg (n=173) for 12 weeks. The mean number of episode-free days (EFD) per patient was significantly greater in the budesonide/formoterol group than the fluticasone group (48.71 compared with 42.34, P=0.0185). Data on medication use, visits to healthcare professionals, and hospitalization were pooled across all six countries and combined with German and Dutch unit cost data to calculate total healthcare costs. Using German unit costs, budesonide/formoterol was associated with significantly lower total healthcare costs per patient over the 12-week period compared with fluticasone (euro 131 compared with euro 210, P=0.0043). Using Dutch unit costs, total healthcare costs were slightly numerically lower in the budesonide/formoterol group than the fluticasone group (euro 102 compared with euro 104), but the difference did not reach statistical significance. Budesonide/formoterol in a single inhaler is more effective than a higher microgram dose of fluticasone alone. It is cost-neutral and may provide cost-savings in some countries.

Fixed and adjustable dose asthma action plans based on combination therapy: A pilot study

The use of combination inhaled corticosteroid/long-acting beta-agonist therapy within the framework of a self-management plan has yet to be investigated. In this randomized open-label study, 69 adult asthmatic patients taking >or= 1,000 microg per day of beclomethasone dipropionate (BDP) or equivalent were treated for 3 months with Symbicort Turbuhaler (200 microg budesonide/6 microg formoterol). Patients were assigned to one of two self-management plans, based on either a fixed or adjustable dose regimen. The primary outcome variable was episode-free days. Both regimens resulted in good asthma control, at least comparable to that obtained with previous high dose inhaled corticosteroid therapy. There were no significant differences in clinical outcome measures between the regimens. The mean (+/- SD) usage of Symbicort was similar for the fixed and adjustable dose regimens (3.8 +/- 0.68 vs 3.6 +/- 1.54 puffs per day, respectively). We conclude that Symbicort is effective when administered as either a fixed or adjustable dose regimen as part of a self-management plan.

Salmeterol/Fluticasone Propionate versus Fluticasone Propionate Plus Montelukast

Asthma, owing to its chronic nature, is associated with a substantial economic burden. Healthcare providers need to compare the cost effectiveness of alternative asthma treatment options to ensure that they obtain the best value for money from the resources they control. The objective of the current study was to compare the cost effectiveness of salmeterol/fluticasone propionate in combination with fluticasone propionate plus montelukast in patients with symptomatic asthma uncontrolled with inhaled corticosteroid (ICS) monotherapy. Direct healthcare resource data were prospectively collected during a double-blind, randomized, 12-week clinical study of inhaled salmeterol/fluticasone propionate 50/100 microg twice daily (n = 356) and inhaled fluticasone propionate 100 microg twice daily plus oral montelukast 10mg daily (n = 369). Resources were costed in Dutch guilders (NLG) from the perspective of The Netherlands healthcare system using 1999/2000 prices, but have been presented in US dollars and euros. The primary effectiveness measure was the proportion of successfully treated weeks (based on mean morning PEF values). Secondary measures were episode-free days, symptom-free days, and symptom-free nights. Salmeterol/fluticasone propionate was more effective than fluticasone propionate plus montelukast as measured by the proportion of successfully treated weeks mean 63.3% vs 39.0%; median difference 25%; p < 0.001). Salmeterol/fluticasone propionate was also more effective than fluticasone propionate plus montelukast according to the secondary effectiveness measures. The mean total direct daily healthcare costs per patient were 16% higher with fluticasone propionate plus montelukast than with salmeterol/fluticasone propionate mainly due to higher drug costs in the former group (2.25 US dollars vs 1.94; 1.92 euro vs 1.66, respectively; the NLG was fixed against the euro at a rate of 1 euro = NLG2.2 on 31 December 1998; 1 US dollars = NLG1.883, June 2003; 1 US dollars= 0.848 euro, June 2003). Incremental cost-effectiveness analyses showed that salmeterol/fluticasone propionate was dominant over fluticasone propionate plus montelukast and sensitivity analyses showed these results to be robust. Salmeterol/fluticasone propionate is a more cost-effective treatment option than fluticasone propionate plus montelukast for patients with symptomatic asthma uncontrolled by ICS.

Effectiveness of budesonide administered via dry-powder inhaler versus triamcinolone acetonide administered via pressurized metered-dose inhaler for adults with persistent asthma in managed care settings

Background: Clinical studies have demonstrated the efficacy and relative safety of inhaled corticosteroids in the treatment of asthma. However, effectiveness and cost-effectiveness comparisons of available inhaled corticosteroids in real-life clinical settings are lacking. Objective: This study compared the effectiveness and safety of budesonide administered via dry-powder inhaler versus that of triamcinolone acetonide administered via pressurized metered-dose inhaler in the treatment of adult patients with persistent asthma treated in a managed care setting. Methods: This was a randomized, open-labe, 52-week study of adult patients (aged ≥ 18 years) with persistent asthma enrolled in 25 US health plans. The primary study outcome was mean change from baseline to the end of treatment in symptom-free days. Secondary variables were changes from baseline in number of episode-free days, episode-free days at 52 weeks, forced expiratory volume in 1 second (FEV 1), forced vital capacity, asthma symptom scores, breakthrough bronchdilator use, patient discontinuations, and health-related quality of life. Patients were issued diaries in which to record use of study medication and concomitant asthma medication use, as well as daytime and nightime asthma symptom severity. Patients were assessed at weeks 4, 13, 26, 39, and 52. Safety was assessed based on adverse events and changes in laboratory tests, vital signs, and physical examinations. Results: A total of 945 patients (344 men, 601 women; mean [SD] age, 46.8 [14] years) were enrolled; 631 received budesonide and 314 received triacinolane acetonide. Improvements in all effectiveness variables were observed with both treatments. The mean increase from baseline in the number of symptom-free days per month assessed at month 12 was 7.74 (95% CI, 6.81–8.66) for patients receiving budesonide and 3.78 (95% CI, 2.47–5.09) for patients receiving triamcinoline acetonide ( P < 0.001). The estimated annual mean (SD) number sympton-free days for patients recieving budesonide was 141.1 (125.0) over the treatment phase, compared with 99.3 (112.1) for those receiving triamcinolone acetonide ( P < 0.001). Patients receiving budesonide demonstrated significant improvements (compared with those receiving triamcinolone acetonide) in overall quality of life, daytime and nightime asthma symptom severity, breakthrough bronchodilator use, and FEV 1 (all P < 0.001). Safety measures were similar between groups. Conclusion: In these managed care settings, budesonide inhalation powder administered via dry-powder inhaler was significantly more effective than triamcinolone acetonide administered via pressurized metered-dose inhaler in the treatment of adults with persistent asthma.

Comparison of the efficacy of formoterol and salmeterol in patients with reversible obstructive airway disease: a multicenter, randomized, open-label trial

Background: Beta 2-adrenergic agonists are frequently used for the prevention and relief of bronchospasm in patients with reversible obstructive airway disease. Formoterol and salmeterol are long-acting beta 2-agonists. In addition to its long duration of action, formoterol has been reported to have an onset of action similar to that of albuterol. Objective: This study compared the effects on lung function of regular twice-daily inhalation of formoterol or salmeterol in adults with moderate to moderately severe persistent asthma who were receiving daily inhaled corticosteroids. Methods: In this 6-month, multicenter, open-label, parallel-group study, patients with moderate or moderately severe asthma were randomized to receive either formoterol 12 μg BID or salmeterol 50 μg BID. The primary end point was mean morning peak expiratory flow (PEF) measured 5 minutes after dosing and entered in a patient diary each day during the first 4 weeks of treatment. Secondary end points included mean morning and evening predose PEF and number of episode-free days recorded in the patient diaries during the first 4 weeks of treatment, use and time of rescue medication, symptom scores, and overall mean morning predose PEF (spirometric measurements made by the physician during scheduled visits) for the entire treatment period. Safety assessments included spontaneously reported adverse events and vital signs. Results: A total of 528 patients were randomized to study treatment, 262 to formoterol and 266 to salmeterol. There were no significant differences in demographic or baseline characteristics between treatment groups, except in the proportion of current smokers in the formoterol group (4.6%) compared with the salmeterol group (1.5%; P = 0.039). Based on the information recorded in patients' diaries, those receiving formoterol showed significant improvement in mean morning PEF measured 5 minutes after dosing ( P < 0.001), reduced use of rescue medication ( P < 0.03), and an increased number of episode-free days ( P < 0.04) compared with patients receiving salmeterol. Mean predose morning and evening PEF and symptom scores based on diary data and mean morning predose PEF based on measurements obtained during office visits were comparable between the 2 treatment groups throughout the study. Conclusions: In this open-label trial, patients randomized to formoterol treatment had greater improvement in mean PEF 5 minutes after dosing, required significantly less rescue medication (fewer actuations of albuterol), and experienced more episode-free days compared with patients receiving salmeterol. Thus, although both formoterol and salmeterol are long-acting beta 2-agonists, formoterol had a more rapid onset of action.

Cost-efficacy comparison of inhaled fluticasone propionate and budesonide in the treatment of asthma

Background: The results of a recent meta-analysis comparing 2 inhaled corticosteroids, fluticasone propionate (FP) and budesonide, demonstrated that FP had an improved efficacy-to-safety ratio compared with budesonide. However, limited data are available on the relative economic benefits of these 2 regimens. Objective: This pharmacoeconomic analysis used individual patient data from studies in the meta-analysis to compare the relative cost-efficacy of 2 asthma regimens from the perspective of a US third-party payer. Methods: This analysis included all 7 studies in the meta-analysis that compared budesonide with FP dosed at approximately half the dose of budesonide and that included measurement of daily morning peak expiratory flow (PEF). Results: The total daily per-person cost of asthma management was higher for patients treated with budesonide than with FP ($3.00 vs $2.25, respectively). Treatment with FP had greater cost-efficacy than treatment with budesonide, based on a range of outcome measures that included improvement in morning PEF, symptom-free days, and episode-free days. The daily cost per effectively treated patient (an increase in PEF of ≥ 10%) was $5.62 with FP and $10.05 with budesonide. The cost per symptom-free day was $4.36 with FP, compared with $6.67 with budesonide. The cost per episode-free day was $5.60 with FP and $9.42 with budesonide. The pharmacoeconomic difference continued to favor FP as the criteria for success were made more stringent and the cost of budesonide was lowered. Conclusion: Based on data from the 7 randomized, controlled trials, treatment of asthma with FP was more effective and less expensive, using US health care assumptions and costs, than treatment with budesonide.

Inhaled salmeterol/fluticasone propionate combination. A pharmacoeconomic review of its use in the management of asthma.

Cost estimates from developed countries indicate that asthma accounts for up to 2% of the economic cost of all diseases. A large proportion of asthma-related costs are attributable to poor asthma control. Treatment strategies which improve clinical outcomes in patients with asthma, therefore, have the potential for significant economic benefits, and it is important to evaluate new asthma therapies for cost effectiveness. Several studies have established that salmeterol and fluticasone propionate combined in a single dry powder inhalation device are at least as effective as a combination of the 2 drugs administered via separate dry powder inhalers and more effective than monotherapy with fluticasone propionate or budesonide. Importantly, pharmacoeconomic analysis of several of these studies show that the salmeterol/fluticasone propionate combination is cost effective relative to monotherapy with fluticasone propionate or budesonide. Although the total cost of asthma management tended to be slightly higher with salmeterol/fluticasone propionate than with inhaled corticosteroid monotherapy, in most cases mean cost-effectiveness ratios were lower (i.e. more favourable) for salmeterol/fluticasone propionate than either fluticasone propionate or budesonide. Cost effectiveness was assessed according to 3 end-points: successfully treated weeks, symptom-free days and episode-free days. Mean cost-effectiveness ratios consistently favoured salmeterol/fluticasone propionate over the comparator drug for the end-point successfully treated weeks, and in most cases the other 2 end-points also favoured the combination product over the comparator. In a further study, salmeterol/fluticasone was also less costly than therapy with formoterol and budesonide administered via 2 separate inhalers. Studies of health-related quality of life (HR-QOL) using the Asthma Quality of Life Questionnaire indicate that salmeterol/fluticasone propionate produces clinically meaningful improvements in overall HR-QOL relative to salmeterol monotherapy or placebo. Improvements in overall HR-QOL were statistically significantly greater for salmeterol/fluticasone propionate than with fluticasone propionate or budesonide alone, although the differences between treatments did not exceed the threshold for clinical significance. In conclusion, short term cost-effectiveness data show that salmeterol/fluticasone propionate is more cost effective than the inhaled corticosteroids budesonide and fluticasone propionate alone. The combination product also appears to improve HR-QOL relative to placebo or salmeterol alone.