Seretide: a pharmacoeconomic analysis

Abstract

Background: The costs of asthma and chronic obstructive pulmonary disease (COPD), the two most common chronic respiratory illnesses, are substantial and rising. The fixed-dose combination of fluticasone and salmeterol has been a safe and effective therapy for these diseases.

Objectives: To review the pharmacoeconomic impact of the fixed-dose combination of inhaled fluticasone and salmeterol in asthma and COPD.

Methods: A systematic review of the literature was carried out to identify pharmacoeconomic studies with fixed-dose salmeterol and fluticasone (Seretide, Advair, Viani). In addition, abstracts from recent respiratory meetings were sought, and any unpublished data were requested from the manufacturer.

Results: For asthma, when compared to treatment with inhaled corticosteroid monotherapy and antileukotrienes, alone or combined, salmeterol/fluticasone inhalation produced a higher proportion of successfully treated weeks, improvement in lung function and quality of life, and fewer treatment failures. The costs per quality-adjusted life year (QALY) for fluticasone/salmeterol have been favourable not only in patients with moderate to severe disease but also in patients with mild disease or patients not previously treated with a maintenance therapy. The excess cost per QALY varied from US$2,670 to US$26,445. For COPD, a clear reduction in exacerbation rates and improvement in quality of life has been demonstrated with salmeterol/fluticasone along with a likely improvement in survival rates. The incremental cost per QALY ratio for fluticasone/salmeterol against placebo ranged from US$9,512 to US$64,038.

Conclusions: The data currently available suggest that the cost effectiveness of combination therapy with fluticasone and salmeterol is favourable for asthma and COPD in a variety of clinical settings.     

Respiratory-related medical expenditure and inpatient utilisation among COPD patients receiving long-acting bronchodilator therapy

Abstract

Objective:

To evaluate chronic obstructive pulmonary disease (COPD)-related expenditure and hospitalisation in COPD patients treated with tiotropium versus alternative long-acting bronchodilators (LABDs).

Methods:

Data were from the Thomson Reuters MarketScan Research Databases. COPD patients ≥35 years with at least one LABD claim between July 1, 2004 and June 30, 2006 were classified into five cohorts based on index LABD: monotherapy with tiotropium, salmeterol/fluticasone propionate, formoterol fumarate, or salmeterol or combination therapy. Demographic and clinical characteristics were evaluated for a 6-month pre-period and COPD-related utilisation and total costs were evaluated for a 12-month follow-up period. LABD relationship to COPD-related costs and hospitalisations were estimated by multivariate generalised linear modelling (GLM) and multivariate logistic regression, respectively.

Results:

Of 52,274 patients, 53% (n?=?27,457) were male, 71% (n?=?37,271) were ≥65?years, and three LABD cohorts accounted for over 90% of the sample [53% (n?=?27,654) salmeterol/fluticasone propionate, 23% (n?=?11,762) tiotropium, and 15% (n?=?7755) combination therapy]. Patients treated with salmeterol/fluticasone propionate (p?<?0.001), formoterol fumarate (p?=?0.032), salmeterol (p?=?0.004), or with combination therapy (p?<?0.001) had higher COPD-related costs and a greater risk of inpatient admission (p?<?0.01 for all) versus tiotropium.

Limitations:

These data are based on administrative claims and as such do not include clinical information or information on risk factors, like smoking status, that are relevant to this population.

Conclusions:

Patients treated with tiotropim had lower COPD-related expenditures and risk of hospitalisation than patients treated with other LABDs     

A budget impact analysis of budesonide/formoterol in patients with mild asthma in Egypt

Abstract

Background: The aim of this study is to estimate the budget impact of budesonide/formoterol fixed dose combination (FDC) vs salbutamol, both used as needed, in mild asthma patients, from the perspective of the Health Insurance Organization (HIO).

Methods: A static budget impact model was developed to assess the impact of budesonide/formoterol FDC entry on HIO budget over a 3-year period in Egyptian settings. Direct medical costs, including the costs of asthma medications, exacerbations, and management of side-effects, were obtained from HIO cost data. Population data were obtained from the World Bank and supplemented with local studies, and the rates of exacerbations, adverse effects, and number of sick leave days were elicited from the SYGMA 1 trial. Scenario analyses from a societal perspective and deterministic sensitivity analyses were conducted.

Results: The total costs (drug and non-drug costs) for managing mild asthma patients from the HIO perspective were estimated to be EGP8.563 billion before budesonide/formoterol entry compared to EGP5.525 billion post-entry, leading to a total budget savings of EGP3.038 billion after 3?years. This total budget saving included an increase in drug costs (EGP104 million) and a decrease in non-drug costs (EGP3.143 billion). Drug costs were higher in the budesonide/formoterol group than in the salbutamol group, but this cost was offset by reductions in non-drug costs, resulting in a reduction in the total costs of healthcare resources. At the societal level, the total budget savings after including the indirect costs was expected to be EGP5.976 billion after 3?years of budesonide/formoterol entry.

Conclusion: Budesonide/formoterol in mild asthma instead of salbutamol produces better patient outcomes and decreases total costs, with increases in drug cost offset by reductions in non-drug costs due to fewer exacerbations. Budesonide/formoterol is a budget saving option for guideline-directed treatment, from the economic perspective of the payer and the health perspective of the patient.     

Cost effectiveness of tiotropium for chronic obstructive pulmonary disease: a systematic review of the evidence

Abstract

Background:

Tiotropium has been shown to reduce exacerbations and improve quality of life for patients with chronic obstructive pulmonary disease (COPD), a lung disease characterized by a persistent and progressive airflow limitation.

Objectives:

To present a systematic literature review of the cost effectiveness of treatment with tiotropium compared with other currently used treatments for COPD.

Methods:

A systematic search was performed via PubMed, the Cochrane database, and EMBASE from 2002 to 2009. Methods and results by study design and by country were compared.

Results:

Seventeen studies were included in the review. Study designs were characterized as follows: modeling based on clinical trial data, and empirical analysis based on either clinical trial or observational data. Comparing monotherapy regimens (12 studies), all study designs found that treatment with tiotropium was associated with lower costs for hospitalisation and other non-drug services. Total costs, including the costs of maintenance drugs, were lower with tiotropium in some, but not all, of the studies. Tiotropium was shown to be cost effective based on commonly accepted benchmark values. Limitations of the review included the wide variety of outcome measures used in different studies, the limited number of observational database studies for monotherapy, and limited data for combination therapy regimens.

Conclusions:

The main conclusions of the economic evaluations derived from clinical trial data at the time of product approval and from later observational data reflecting clinical use are similar: use of tiotropium monotherapy is associated with lower hospital and other non-drug costs and better health outcomes and is either cost saving or cost effective compared with other maintenance monotherapies.     

联合吸入沙美特罗替卡松与噻托溴铵治疗重度慢性阻塞性肺疾病缓解期疗效观察

目的观察联合吸入沙美特罗替卡松和噻托溴铵治疗重度慢性阻塞性肺疾病缓解期的疗效。方法将60例确诊为重度COPD缓解期患者随机分为沙美特罗替卡松组、噻托溴铵组及沙美特罗替卡松联合噻托溴铵组,分别给予相对应的药物治疗6个月。记录三组治疗前后肺功能、血气分析及不良反应。结果三组COPD患者经治疗后肺功能均有改善,而沙美特罗替卡松和噻托溴铵联合吸入组比单用沙美特罗替卡松或噻托溴铵肺功能改善更显著(P<0.05),且无严重不良反应。结论联合吸入沙美特罗替卡松和噻托溴铵治疗重度慢性阻塞性肺疾病缓解期疗效显著,无严重不良反应。     

Systematic review of models used in economic analyses in moderate-to-severe asthma and COPD

Background:

Respiratory diseases exert a substantial burden on society, with newer drugs increasingly adding to the burden. Economic models are often used, but seldom reviewed.

Purpose:

To summarize economic models used in economic analyses of drugs treating moderate-to-severe/very severe asthma or chronic obstructive pulmonary disease (COPD).

Methods:

This study searched Medline and Embase from inception to the end of February 2015 for cost-effectiveness/utility analyses that examined at least one drug against placebo, another drug, or other standard therapy in asthma or COPD. Two reviewers independently searched and extracted data with differences adjudicated via consensus discussion. Data extracted included model used and its qualities, validation methods, treatments compared, disease severity, analytic perspective, time horizon, data collection (pro- or retrospective), input rates and sources, costs and sources, planned sensitivity analyses, criteria for cost-effectiveness, reported outcomes, and sponsor.

Results:

This study analyzed 53 articles; 14 (25%) on asthma and 39 (75%) COPD. Markov models were commonly used for both asthma and COPD-related economic evaluations. Relatively few studies validated their model. For asthma-related studies, 10 examined inhaled corticosteroids and nine studied omalizumab. Placebo or standard therapy was the comparison in 11 studies and active drugs in the remainder.

Conclusions:

Few studies include validation of their models. Furthermore, controversy concerning some results was uncovered in this study, which needs to be avoided in the future.     

Economic impact of using inhaled corticosteroids without prior exacerbation among elderly patients with chronic obstructive pulmonary disorder

Abstract

Objective:

To assess the economic impact of initiating inhaled corticosteroids (ICS) without evidence of prior exacerbation among elderly patients with chronic obstructive pulmonary disease (COPD) in the US.

Methods:

This retrospective study used administrative claims to identify newly diagnosed COPD patients between 1/1/2005 and 6/30/2006 who were dispensed ICS. The dispense date of the first ICS was set as the index date. Patients with prior diagnoses for asthma, cystic fibrosis, or lung cancer were excluded. Cohorts were constructed based on whether ICS therapy was concordant with recommended guidelines of having prior COPD exacerbation. Each COPD patient with prior exacerbation was matched to four patients without exacerbation based on age, gender, Charlson Comorbidity Index, and whether COPD diagnosis code was not elsewhere specified (i.e., 496). Multivariate regressions were estimated to assess the association between use of ICS therapy without prior exacerbation and total healthcare costs, controlling for demographics and clinical characteristics.

Results:

The study included 3650 patients: 730 with prior exacerbation and 2920 without prior exacerbation. Patients were 76 years of age and 54% were male. Those with prior exacerbation were more likely to have inpatient stays both prior to (74.4 vs. 44.1%, p?<?0.05) and following (37.0 vs. 33.1%, p?<?0.05) the index date. Controlling for patient characteristics, patients who were dispensed ICS without prior exacerbation had $1859 higher in total costs (p?<?0.05) compared to patients with prior exacerbation during the 12 months following ICS initiation.

Limitations:

The retrospective design of this study limits the interpretation of findings as association and not causality. This study is subject to selection bias due to unobservable confounders.

Conclusions:

Among COPD patients, initiation of ICS without prior exacerbation appears to be associated with increased healthcare costs. These findings suggest that ICS initiation without evidence of exacerbation as consistent with guidelines is associated with adverse economic consequences.     

Healthcare utilization and costs among chronic bronchitis patients treated with maintenance medications from a US managed care population

Abstract

Objectives:

This study aimed to examine the real-world healthcare resource utilization (HCRU) and direct costs among chronic bronchitis (CB) patients treated with chronic obstructive pulmonary disease (COPD) maintenance medications.

Methods:

This retrospective analysis utilized administrative claims data from 14 US commercial managed care plans. Eligible patients were ≥40 years old, had ≥2 years of continuous enrollment, ≥1 CB (ICD-9-CM code 491.xx) hospitalization or emergency department (ED) visit or ≥2 office visits between 1/1/2004 and 5/31/2011, and had ≥2 pharmacy fills for COPD medications during follow-up (first fill served as the index date). All-cause and COPD-related HCRU and costs were assessed during follow-up. Multivariate models were utilized to identify predictors of total costs.

Results:

Treated CB patients (n?=?17,382; 50.6% female; mean age 66.7 (SD?=?11.4) years) had a mean of 7.6 (SD?=?6.3) COPD maintenance medication fills during follow-up. Overall, 32.6% of patients had ≥1 COPD-related inpatient hospitalizations, 12.9% had ≥1 ED visit, and 81.8% had ≥1 office visit. Mean all-cause and COPD-related total costs were $25,747 (SD?=?$51,105) and $12,609 (SD?=?$36,801), respectively, during follow-up. Among the sub-group with ≥1 exacerbation during baseline year, 42.3% had ≥1 COPD-related inpatient hospitalization, 18.5% had ≥1 ED visit, and 88.2% had ≥1 office visit. Mean follow-up all-cause and COPD-related total costs were $29,861 (SD?=?$49,799) and $16,784 (SD?=?$34,170), respectively. The number of baseline exacerbations was a significant predictor of all-cause and COPD-related total costs during follow-up.

Limitations:

This study lacked standard measures of CB severity; however, severity proxies were utilized.

Conclusion:

HCRU and costs among CB patients were substantial during follow-up, despite treatment with COPD maintenance medications. Additional interventions aiming to prevent or reduce HCRU and costs among CB patients warrant exploration.     

Cost-effectiveness analysis of roflumilast/tiotropium therapy versus tiotropium monotherapy for treating severe-to-very severe COPD

Abstract

Objective:

To conduct a cost-effectiveness analysis comparing roflumilast/tiotropium therapy vs tiotropium monotherapy in patients with severe-to-very severe COPD.

Methods:

The economic evaluation applied a disease-based Markov cohort model with five health states: (1) severe COPD, (2) severe COPD with a history of severe exacerbation, (3) very severe COPD, (4) very severe COPD with a history of severe exacerbation, and (5) death. Within a given health state, a patient may have a mild/moderate or severe exacerbation or die. Data from roflumilast clinical trials and published literature were used to populate model parameters. The model calculated health outcomes and costs for roflumilast/tiotropium therapy vs tiotropium monotherapy over a 5-year horizon. Incremental cost and benefits were then calculated as cost-effectiveness ratios, including cost per exacerbation avoided and cost per quality adjusted life year ($/QALY).

Results:

Over a 5-year horizon, the estimated incremental costs per exacerbation and per severe exacerbation avoided were $589 and $5869, respectively, and the incremental cost per QALY was $15,815. One-way sensitivity analyses varying key parameters produced an incremental cost per QALY ranging from $1963–$32,773.

Limitations:

A number of key parameters used in the model were obtained from studies in the literature that were conducted under different contexts. Specifically, the relative risk estimate for severe COPD patients originates from a small trial not designed to demonstrate the impact of roflumilast on frequency of exacerbations. In addition, the model extrapolates the relative risk estimates over periods of 5–30 years, even though the estimates were only observed in trials that spanned less than a year.

Conclusions:

The addition of roflumilast to tiotropium is cost-effective for the treatment of severe to very severe COPD patients.     

Incremental third-party costs associated with COPD exacerbations: a retrospective claims analysis

Abstract

Background:

Exacerbations are a major contributor to the large burden of treating chronic obstructive pulmonary disease (COPD). Estimates of exacerbation costs in the United States are limited.

Objective:

To estimate incremental costs associated with COPD exacerbation, particularly severe exacerbation, in the United States.

Methods:

COPD patients with at least one exacerbation were identified in the Thomson Reuters MarketScan administrative claims database. A COPD exacerbation was defined as patient use of oral or parenteral corticosteroids on the same day or within 7 days following a claim with a COPD diagnosis. Severe exacerbation was further defined if the exacerbation was associated with hospitalization or death. Healthcare costs and exacerbations were evaluated at quarterly intervals starting from patients’ first observed claim with COPD diagnostic code in the database. Incremental costs associated with exacerbation were estimated as cost differences between quarters with exacerbation and quarters without exacerbation.

Results:

A total of 2644,174 patient-quarters, derived from 228,978 COPD patients, were included in the analysis. The average patient was followed an average of 2.9 years. The mean total cost was $17,016 per patient-quarter with severe exacerbation, $6628 per patient-quarter with non-severe exacerbation, an average of $8726 per patient-quarters with any exacerbation compared to $4762 per patient-quarter with no exacerbation. After adjusting for patient demographics, the mean incremental total cost was $11,261 per patient-quarter with severe exacerbation, $1509 per patient-quarter for non-severe exacerbation, and $3439 per patient-quarter with any exacerbation compared with patient-quarters with no exacerbation.

Limitations:

The method used for defining exacerbations does not capture mild exacerbations. Additional limitations exist due to the nature of claims data.

Conclusions:

Exacerbations, especially severe ones, result in a significant economic burden for third-party payers. Effective management of COPD and prevention of exacerbations may lead to improved patient outcomes and reduction in total healthcare costs for long-term management of COPD.     

Cost-effectiveness of omalizumab for uncontrolled allergic asthma in the Netherlands

Abstract

Background:

Omalizumab, licensed for patients with uncontrolled persistent allergic (IgE mediated) asthma, was found to be cost-effective based upon its clinical trial data. Observational studies have been undertaken to determine the real life outcomes of using omalizumab in the community.

Objective:

To determine the cost-effectiveness of omalizumab based upon observational data from the Netherlands and compare to its cost-effectiveness using clinical trial data.

Methods:

An observational study (eXpeRience) recruited allergic asthma patients eligible for Omalizumab therapy and followed them while on treatment. At 1 year, data from the Dutch patients enrolled in eXpeRience were examined to estimate the number of exacerbations and resource use while on omalizumab therapy compared to the year prior to omalizumab use. Observational data were used in a Markov model to calculate the lifetime cost-effectiveness ratios.

Results:

In the 1 year prior to omalizumab therapy the per-person rate of exacerbations was 3.39 compared to 1.07 in the year taking omalizumab. The discounted incremental lifetime additional costs for omalizumab were €55,865 for 1.46 additional quality-adjusted life years (QALY), resulting in €38,371/QALY. Using the INNOVATE clinical trial outcomes and current resource use, the prior ratio was €34,911/QALY, similar to the observational ratio. As in all observational studies, the main limitation is obtaining complete and accurate data. Patients with missing exacerbation or response data were excluded from this analysis.

Conclusion:

Non-clinical trial experience with omalizumab supported the finding of fewer exacerbations in the allergic asthma population while treated with omalizumab, and therapy was found to continue to have an attractive cost-effectiveness ratio.     

Risk of all-cause hospitalization in COPD patients initiating long-acting or short-acting beta agonist therapy

Abstract

Objective:

This retrospective claims study investigated the rates of all-cause hospitalization among chronic obstructive pulmonary disease (COPD) patients initiating treatment with short-acting beta agonists (SABA) or long-acting beta agonists (LABA).

Methods:

Data from the 5% national sample of Medicare enrollees for 2006–2008 were used. Patients initiating COPD therapy were identified as those with no COPD therapy for ≥ 6-months prior to initiating SABA or LABA (administered via dry-powder inhalers, metered-dose inhalers, or nebulizer) treatment. All patients were continuously eligible for Medicare Parts A, B, and D for 18 months. Those enrolled in Medicare Advantage, who had asthma, or were < 65 years old were excluded. Differences in the rates of all-cause hospitalizations and time to all-cause hospitalization during the 6-month follow-up period were examined, while adjusting for demographics, clinical indicators, and health service use.

Results:

Among 3017 COPD patients who met the inclusion criteria, 883 (30%) were LABA users and 2134 (70%) were SABA users. Overall, 21% of patients (16% [144/883] of LABA and 23% [492/2134] of SABA) had a hospitalization during the follow-up period. Mean time to hospitalization was 86 days for LABA vs 64 days for SABA patients (p?<?0.05). The adjusted hazard ratio for hospitalization in a Cox proportional hazards model was 0.74 (95% CI?=?0.62–0.90) for patients treated with LABA vs. SABA.

Limitations:

The analysis was adjusted for multiple background characteristics, but important measures of severity in COPD, such as measures of lung functioning, were not available and may have differed between patients treated with LABA or SABA.

Conclusions:

The results of this analysis indicate COPD patients initiating LABA treatment had a longer time to all-cause hospitalization and a 26% lower risk of hospitalization during the 6-months follow-up period compared to those initiating SABA therapy.     

Budget impact of erlotinib for maintenance therapy in advanced non-small cell lung cancer

Abstract

Objective:

Assess the budgetary impact of adding erlotinib for maintenance therapy (MTx) in advanced non-small cell lung cancer (NSCLC) from a US health plan perspective.

Methods:

A budget impact model was developed to analyze the costs (drug, administration, adverse events) associated with adding erlotinib MTx to a hypothetical 500,000 member US health plan. Treatment durations and dosing were derived from randomized controlled trials, FDA labeling, and National Comprehensive Cancer Network guidelines. Treatment patterns and assumptions were based on market research data, the SEER registry, and published literature. Cost data were obtained from Centers for Medicare and Medicaid Services payment rates and a drug pricing database. Sensitivity analyses were conducted to assess uncertainty.

Results:

Overall health plan expenditures increased by $0.010 per member per month (PMPM). The main driver of additional cost was the erlotinib drug cost (～$66,000) with the administration ($464) and side-effect ($47) costs being relatively modest. One-way sensitivity analyses showed that the results were most sensitive to the proportion of members receiving MTx; however, the PMPM did not exceed $0.013.

Conclusions:

The overall budget impact to a health plan of expanding the use of erlotinib from the 2nd/3rd-line advanced NSCLC setting to include the maintenance setting was relatively small. This was primarily due to the proportion of patients who would receive erlotinib MTx, the low cost of side-effects and minimal cost of drug administration. Additional research may be warranted to estimate the relative clinical and economic impacts of erlotinib MTx versus alternative MTx treatments.     

Comparative cost analysis of management of secondary hyperparathyroidism with paricalcitol or cinacalcet with low-dose vitamin D in hemodialysis patients

Abstract

Objective:

The objective of this analysis was to compare costs of paricalcitol or cinacalcet plus low dose vitamin D, and of phosphate binders, in patients in the IMPACT SHPT study; and to extrapolate those to estimate expected annual maintenance costs.

Methods:

IMPACT SHPT was a 28-week, randomized, open-label trial. Subjects from 12 countries received intravenous (IV) or oral paricalcitol, or oral cinacalcet plus fixed IV doxercalciferol or oral alfacalcidol. The primary end-point was the proportion of subjects who achieved a mean intact parathyroid hormone (iPTH) value of 150–300?pg/mL during weeks 21–28 (evaluation period). This study compares the costs of study drugs and phosphate binders among participants during the study and annualized. This analysis includes only those subjects that reached the evaluation period (134 in each group).

Results:

The mean total drug costs over the study period were €2606 (SD?=?€2000) in the paricalcitol group and €3034 (SD?=?€3006) in the cinacalcet group (difference €428, p?=?0.1712). The estimated annualized costs were €5387 (SD?=?€4139) in the paricalcitol group and €6870 (SD?=?€6256) in the cinacalcet group (difference €1492, p?=?0.0395). In addition, a significantly greater proportion (p?=?0.010) of subjects in the paricalcitol arm (56.0%) achieved an iPTH of 150–300?pg/mL during the evaluation period compared to the cinacalcet arm (38.2%).

Limitations:

This was a secondary analysis of the IMPACT SHPT study which was not designed or powered for costs as an outcome. The dosing of study drugs and phosphate binders in the IMPACT study may not reflect actual practice, and patients were followed for 28 weeks, while the treatment of SHPT is long-term.

Conclusion:

Patients with SHPT requiring hemodialysis who were treated with a paricalcitol-based regimen for iPTH control had lower estimated annual drug costs compared to those treated with cinacalcet plus low-dose vitamin D.     

Bambuterol is a more cost-effective treatment strategy than salmeterol in asthmatic patients with nocturnal symptoms

Summary

We aimed to compare the cost-effectiveness of oral bambuterol (Bambec®) 20?mg once daily with that of salmeterol (Serevent®) via pressurised metered dose inhaler (pMDI) 50?µg twice daily for treatment of asthma patients with nocturnal symptoms. One hundred and twenty six patients aged 18-70 years and using inhaled corticosteroids at a constant daily dose and with forced expiratory volume in one second (FEV1) 40-85% of predicted normal value, were included in this double-blind, randomised, parallel-group study (two weeks' run-in, six weeks' treatment) in the United Kingdom, Italy and Norway. During run-in, they had to have a nocturnal awakening or early awakening due to asthma symptoms that required rescue medication at least once during a two-week run-in period, and a > 15% fall in overnight peak expiratory flow (PEF) on at least three out of the last seven days. Morning and evening PEF were measured and tremor was scored. The effectiveness variables in the cost-minimisation analysis were symptom-free days and number of nights with no awakenings. Costs for both study and rescue medication were calculated.

There were no statistically significant differences between bambuterol and salmeterol regarding morning and evening PEF (change from baseline), tremor, and the effectiveness variables. Mean number of symptom-free days was 25% vs. 20% and mean number of nights with no awakenings was 69% vs. 77% in the bambuterol and salmeterol groups, respectively. However treatment costs (study plus rescue medication) were lower during bambuterol treatment in all three countries. The per patient cost savings would be 47% in the UK, 27% in Italy and 40% in Norway if a patient changes from salmeterol to bambuterol. The conclusion is that the once-daily treatment with bambuterol is more cost-effective than the twice-daily treatment with salmeterol in asthma patients with nocturnal symptoms.