A US database study characterizing patients initiating a budesonide-formoterol combination versus tiotropium bromide as initial maintenance therapy for chronic obstructive pulmonary disease.

OBJECTIVE: To compare clinical and demographic characteristics, resource utilization and costs of chronic obstructive pulmonary disease (COPD) patients prior to initiating budesonide-formoterol combination (BFC) or tiotropium-maintenance therapy. MATERIALS AND METHODS: This cross-sectional study used claims-based diagnosis to identify COPD patients in the HealthCore Integrated Research Database who initiated BFC or tiotropium therapy between March 1, 2009 and January 31, 2012 (intake period); the index date was defined as the initial prescription fill for either agent. Patients diagnosed with respiratory tract cancer or receiving inhaled corticosteroids/long-acting ß2-adrenergic agonists or tiotropium in 12 months prior to index date were excluded. Categorical variables were evaluated with χ(2) tests; mean cost differences were evaluated using γ-regression. RESULTS: Overall, 6,940 BFC and 10,831 tiotropium patients were identified. The BFC group was younger (mean age 64 versus 67 years), with a greater proportion of females (54% versus 51%). BFC-treated patients had more comorbid respiratory conditions, including asthma (25% versus 13%), but fewer comorbid cardiovascular conditions, including atherosclerosis (7% versus 10%) and myocardial infarction (4% versus 6%). A greater proportion of BFC patients received prior respiratory medication, including oral corticosteroids (46% versus 35%) and short-acting ß2-agonists (44% versus 35%). Tiotropium-treated patients had a greater mean number of COPD-related outpatient visits (4.6 versus 4.1). BFC-treated patients had lower total all-cause ($17,259 versus $17,926) and COPD-related ($1,718 versus $1,930) health care costs, driven by lower all-cause and COPD-related inpatient expenditures. CONCLUSION: Initiators of BFC or tiotropium showed differences in clinical and demographic characteristics and health care utilization and costs prior to starting COPD maintenance therapy.

Cost-utility analysis of tiotropium versus usual care in patients with COPD in the UK and Belgium.

OBJECTIVE: To evaluate the cost-utility of adding tiotropium to usual care versus usual care alone for patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in the UK and Belgium. METHODS: A four-state Markov model was developed with three disease severity states (moderate, severe, very severe) and death. Severity was based on post-bronchodilator FEV1 and transitions were based on outcomes of the Understanding Potential Long Term Impacts on Function with Tiotropium (UPLIFT®) trial. Utilities were derived from EQ-5D scores for a subset of UPLIFT® patients. UK costs were evaluated separately for England (E), and for Scotland, Wales and Northern Ireland (SWNI). Belgian (B) costs were obtained from local sources. Uncertainty was assessed by deterministic and probabilistic sensitivity analysis (PSA). RESULTS: Adding tiotropium to usual care resulted in an incremental cost per patient of €969 (B), £796 (E), and £812 (SWNI), and incremental QALYs of 0.052 (B), and 0.051 (E, SWNI). The four-year incremental cost-effectiveness ratios (ICER) were €18,617 (B), £15,567 (E) and £15,890 (SWNI) per QALY. Probability of tiotropium being cost-effective at £30,000 (€50,000) per QALY gained was greater than 60%. CONCLUSIONS: At willingness to pay thresholds of £(€) 30,000 per QALY gained, adding tiotropium to usual care is cost-effective.

Tiotropium versus long-acting beta-agonists for stable chronic obstructive pulmonary disease.

BACKGROUND: Tiotropium and long-acting beta(2)-agonists (LABAs) are both accepted in the routine management for people with stable chronic obstructive pulmonary disease (COPD). There are new studies which have compared tiotropium with LABAs, including some that have evaluated recently introduced LABAs. OBJECTIVES: To compare the relative clinical effects of tiotropium bromide alone versus LABA alone, upon measures of quality of life, exacerbations, lung function and serious adverse events, in people with stable COPD.To critically appraise and summarise current evidence on the costs and cost-effectiveness associated with tiotropium compared to LABA in people with COPD. SEARCH METHODS: We identified randomised controlled trials (RCTs) from the Cochrane Airways Group Specialised Register of trials and economic evaluations from searching NHS EED and HEED (date of last search February 2012). We found additional trials from web-based clinical trial registers. SELECTION CRITERIA: We included RCTs and full economic evaluations if they compared effects of tiotropium alone with LABAs alone in people with COPD. We allowed co-administration of standard COPD therapy. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, then extracted data on study quality and outcomes. We contacted study authors and trial sponsors for additional information. We analysed data using the Cochrane Review Manager(RevMan 5.1) software. MAIN RESULTS: Seven clinical studies totalling 12,223 participants with COPD were included in the review. The studies used similar designs and were generally of good methodological quality. Inclusion criteria for RCTs were similar across the included studies, although studies varied in terms of smoking history and COPD severity of participants. They compared tiotropium (which was delivered by HandiHaler in all studies) with salmeterol (four studies, 8936 participants), formoterol (one study, 431 participants) and indacaterol (two studies, 2856 participants). All participants were instructed to discontinue anticholinergic or long-acting beta(2)-agonist bronchodilators during treatment, but could receive inhaled corticosteroids (ICS) at a stable dose. Study duration ranged from 3 to 12 months. We extracted data for 11,223 participants. In general, the treatment groups were well matched at baseline. Overall, the risk of bias across the included RCTs was low.In the analysis of the primary outcomes in this review, a high level of heterogeneity amongst studies meant that we did not pool data for St George's Respiratory Questionnaire quality of life score. Subgroup analyses based on the type of LABA found statistically significant differences among effects on quality of life depending on whether tiotropium was compared with salmeterol, formoterol or indacaterol. Tiotropium reduced the number of participants experiencing one or more exacerbations compared with LABA (odds ratio (OR) 0.86; 95% confidence interval (CI) 0.79 to 0.93). For this outcome, there was no difference seen among the different types of LABA. There was no statistical difference in mortality observed between the treatment groups.For secondary outcomes, tiotropium was associated with a reduction in the number of COPD exacerbations leading to hospitalisation compared with LABA treatment (OR 0.87; 95% 0.77 to 0.99), but not in the overall rate of all-cause hospitalisations. There was no statistically significant difference in forced expiratory volume in one second (FEV(1)) or symptom score between tiotropium and LABA-treated participants. There was a lower rate of non-fatal serious adverse events recorded with tiotropium compared with LABA (OR 0.88; 95% CI 0.78 to 0.99). The tiotropium group was also associated with a lower rate of study withdrawals (OR 0.89; 95% CI 0.81 to 0.99).We identified six full economic evaluations assessing the cost and cost-effectiveness of tiotropium and salmeterol. The studies were based on an economic model or empirical analysis of clinical data from RCTs. They all looked at maintenance costs and the costs for COPD exacerbations, including respiratory medications and hospitalisations. The setting for the evaluations was primary and secondary care in the UK, Greece, Netherlands, Spain and USA. All the studies estimated tiotropium to be superior to salmeterol based on better clinical outcomes (exacerbations or quality of life) and/or lower total costs. However, the authors of all evaluations reported there was substantial uncertainty around the results. AUTHORS' CONCLUSIONS: In people with COPD, the evidence is equivocal as to whether or not tiotropium offers greater benefit than LABAs in improving quality of life; however, this is complicated by differences in effect among the LABA types. Tiotropium was more effective than LABAs as a group in preventing COPD exacerbations and disease-related hospitalisations, although there were no statistical differences between groups in overall hospitalisation rates or mortality during the study periods. There were fewer serious adverse events and study withdrawals recorded with tiotropium compared with LABAs. Symptom improvement and changes in lung function were similar between the treatment groups. Given the small number of studies to date, with high levels of heterogeneity among them, one approach may be to give a COPD patient a substantial trial of tiotropium, followed by a LABA (or vice versa), then to continue prescribing the long-acting bronchodilator that the patient prefers. Further studies are needed to compare tiotropium with different LABAs, which are currently ongoing. The available economic evidence indicates that tiotropium may be cost-effective compared with salmeterol in several specific settings, but there is considerable uncertainty around this finding.

Pharmacoeconomic evaluation of tiotropium bromide in the long-term treatment of chronic obstructive pulmonary disease (COPD) in Italy.

The randomized, double-blind trial UPLIFT(®) demonstrated in 5,993 patients with moderate to very severe COPD that 4 years of tiotropium bromide therapy were associated with improvements in lung function, exacerbations, quality of life, and mortality compared with placebo. The pharmacoeconomic evaluation was performed through a probabilistic, patient-level simulation Markov model. Routine COPD care (RC) was compared with the inclusion of tiotropium bromide on it. The analysis was conducted over a lifetime horizon, with 1 year cycles and a 3.5% annual discount rate. Patients were characterized by gender, age, height, smoking status, and forced expiratory volume in 1 s (FEV1). FEV1 time trend was modeled according to the annual decline recorded in UPLIFT®. Mortality derived from that of the general Italian population was adjusted by smoking status and FEV1. Health utilities derived from published Italian observational studies and were varied in time according to UPLIFT® data. Exacerbation rates were derived from a published Italian observational prospective study. The cost perspective was that of the Italian National Health Service. Healthcare resource consumption for RC and exacerbations derived from Italian observational studies were valued according to current price and tariffs. Simulated patients in the tiotropium arm gained an average (95% CI) 0.50 (-1.63 to 6.27) Life Years (LYs) and 0.42 (-0.25 to 3.05) Quality-Adjusted Life Years (QALYs). The incremental lifetime cost resulted €3,357 (-€10,669 to €29,820). The incremental cost-effectiveness ratio (ICER) was €6,698/LY and €7,916/QALY. In the cost-effectiveness acceptability curve (CEAC), tiotropium had a 90% probability of being cost-effective for a willingness to pay (WTP) threshold of € 10,000/QALY.

Trends in health care utilization in British Columbia following public coverage for tiotropium.

OBJECTIVES: To examine the use and cost of health-care services in British Columbia, Canada, before and after public drug coverage for tiotropium bromide. METHODS: A time series analysis was performed using data from British Columbia's centralized administrative health-care databases. Linear regression on data from a stable 3-year prepolicy period was used to predict future use of inhaled anticholinergic (IAC) medications, visits to physicians, emergency hospitalizations, and costs. For each use measure, we estimated the policy effect as the difference between observed use in the postpolicy period and predicted use obtained from the prepolicy period. RESULTS: In total, over the 2.5-year period after public coverage, tiotropium use increased by 24.4% more than predicted (95% confidence interval [CI] 23.9%-24.8%). Visits to physicians were unchanged, but there were between 596 and 948 more emergency admissions for chronic obstructive pulmonary disease, and between 582 and 1940 more hospital admissions of any kind than were predicted from prepolicy data. Total cost of inhaled IAC medications increased slightly more than predicted, by between an additional CDN$1.30 million and CDN$1.71 million, but total out-of-pocket spending by patients on IAC medications was reduced by between CDN$2.83 million and CDN$3.11 million because of public coverage. Hospital costs were between CDN$3.88 million and CDN$12.93 million greater than anticipated based on prepolicy data. CONCLUSIONS: Public drug plan coverage for tiotropium in British Columbia reduced out-of-pocket costs for patients and their private insurers. Before versus after time series analysis did not show a reduction in hospitalizations or physician visits, or costs associated with those services.

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

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.

Healthcare costs associated with initial maintenance therapy with fluticasone propionate 250 µg/salmeterol 50 µg combination versus anticholinergic bronchodilators in elderly US Medicare-eligible beneficiaries with COPD.

OBJECTIVE: To compare, in elderly Medicare beneficiaries, chronic obstructive pulmonary disease (COPD)-related healthcare costs for patients initiating treatment with fluticasone propionate/salmeterol 250 µg/50 µg (FSC) with those for patients initiating treatment with ipratropium bromide/albuterol (IPA), ipratropium bromide (IPR), and tiotropium bromide (TIO). METHODS: In this retrospective, observational, cohort study, COPD-related medical costs (inpatient/emergency department, outpatient) and pharmacy costs were assessed in Medicare beneficiaries ≥ 65 years old who were enrolled in a commercial Medicare health maintenance organization plan and had a diagnosis of COPD (ICD-9-CM codes 491.xx, 492.xx, or 496.xx) within 12 months before initial treatment with FSC, IPA, IPR, or TIO. RESULTS: In these ≥ 65-year-old patients (N=14,689), initial maintenance treatment with FSC was associated with total COPD-related cost savings (medical + pharmacy) of $295 versus IPA, $1,235 versus IPR, and $110 versus TIO (p<0.05, each comparison) over a 1-year follow-up period. CONCLUSIONS: Initiation of maintenance therapy with FSC was associated with significant reduction in total costs (medical + pharmacy) relative to costs associated with the short-acting anticholinergic bronchodilators IPR and IPA and the long-acting anticholinergic bronchodilator TIO in an elderly Medicare-eligible population. These data considered in the context of the substantial efficacy and effectiveness data suggest that early introduction of maintenance treatment with FSC has both clinical and economic benefits. Limitations inherent in handling of administrative data include lack of objective clinical measures such as spirometry and smoking status. Furthermore, accuracy of diagnosis codes cannot be verified.

Modelling the 5-year cost effectiveness of tiotropium, salmeterol and ipratropium for the treatment of chronic obstructive pulmonary disease in Spain.

Our objective was to assess the 5-year cost effectiveness of bronchodilator therapy with tiotropium, salmeterol or ipratropium for chronic obstructive pulmonary disease (COPD) from the perspective of the Spanish National Health System (NHS). A probabilistic Markov model was designed wherein patients moved between moderate, severe or very severe COPD and had the risk of exacerbation and death. Probabilities were derived from clinical trials. Spanish healthcare utilisation, costs and utilities were estimated for each COPD and exacerbation state. Outcomes were exacerbations, exacerbation-free months, quality-adjusted life years (QALYs), and cost(-effectiveness). The mean (SE) 5-year number of exacerbations was 3.50 (0.14) for tiotropium, 4.16 (0.40) for salmeterol and 4.71 (0.54) for ipratropium. The mean (SE) number of QALYs was 3.15 (0.08), 3.02 (0.15) and 3.00 (0.20), respectively. Mean (SE) 5-year costs were 6,424 euro (305 euro) for tiotropium, 5,869 euro (505 euro) for salmeterol, and 5,181 euro (682 euro) for ipratropium (2005 values). Ipratropium and tiotropium formed the cost-effectiveness frontier, with tiotropium being preferred when willingness to pay (WTP) exceeded 639 euro per exacerbation-free month and 8,157 euro per QALY. In Spain, tiotropium demonstrated the highest expected net benefit for ratios of the willingness to pay per QALY, well within accepted limits.

Cost reduction strategies used by elderly patients with chronic obstructive pulmonary disease to cope with a generic-only pharmacy benefit.

BACKGROUND: Generic-only pharmacy benefits may present more of a burden to patients with chronic disease conditions such as chronic obstructive pulmonary disease (COPD), where generic drug therapy choices are more limited. OBJECTIVE: To evaluate the strategies that elderly patients with COPD use to manage their out-of-pocket (OOP) prescription expenses in a generic-only pharmacy benefit compared with similar patients with a single-tier copayment or a 2-tier pharmacy benefit with coverage of brand formulary drugs. METHODS: Surveys were mailed to a sample of 3,000 Kaiser Permanente (California) patients (aged > or = 65 years) who had a diagnosis for COPD and received at least 1 prescription for a COPD-related medication during 2003. The sample was stratified by type of pharmacy benefit: generic-only, single copayment tier, and 2 copayment tiers. The survey contained questions about strategies used to reduce OOP prescription expenses, such as stop taking a prescribed medication, purchase prescriptions out of the country, or discuss OOP prescription expenses with a physician. The likelihood of using specific strategies to reduce OOP prescription expenses was modeled using logistic regression. Covariates included social support, quality of life, smoking status, socioeconomic status, total prescription costs, and demographics. RESULTS: A total of 1,624 surveys were returned, for a 54% response rate. Results from logistic regressions indicate that COPD patients with a generic-only benefit are significantly more likely to report that they discussed their OOP costs with their physician (odds ratio [OR]=9.02; 95% confidence interval [CI], 6.15- 13.22), purchased their medications from another country (OR=6.70; 95% CI, 3.17-14.16) and reduced spending on food and clothing (OR=4.06; 95% CI, 2.70-6.12). They are also more likely to report that they had taken less than the prescribed amount of a regular medication (OR=1.70; 95% CI, 1.25-2.31) and that they stopped taking one or more of their regular medications (OR=1.77; CI, 1.27-2.47). Patients with low annual household incomes (<25,000 US dollars) were significantly more likely to discuss their OOP costs with their physician (OR=1.47; 95% CI, 1.08-2.00 ) and to reduce spending on food and clothing (OR=1.97; 95% CI, 1.42-2.73) than those with higher incomes. Approximately 15% of COPD patients obtained drug samples from their physicians as a method to reduce OOP costs, and there was no difference among the 3 groups in the prevalence of this cost management strategy. Overall, patients in the generic-only pharmacy benefit used an average of 3 methods to reduce OOP pharmacy costs compared with approximately 1.5 cost reduction methods used by patients in single-tier and 2-tier copayment designs who had coverage of formulary brand as well as generic drugs. CONCLUSION: Elderly patients with COPD and a generic-drug-only pharmacy benefit are more likely to report using a variety of strategies to reduce their OOP costs compared with similar patients with single-tier copayment or 2-tier copayment pharmacy benefits. The most common strategy was discussing OOP costs with their physician, and use of this strategy was inversely related to household income. There was no difference in the proportion of COPD patients among the 3 pharmacy benefit groups that used drug samples from their physicians as a means to reduce OOP costs.

[Cost-effectiveness analysis of tiotropium compared to ipratropium and salmeterol]. / Análisis del coste-eficacia del tiotropio frente al ipratropio y salmeterol.

OBJECTIVE: The constant increase in health care costs, in a context of limited resources and the appearance of more costly though more effective drugs, justifies an assessment of the pharmacoeconomics of these drugs. The objective of this study was to evaluate the cost-effectiveness of one of the newest drugs for the treatment of chronic obstructive pulmonary disease (COPD)-tiotropium. MATERIAL AND METHOD: A cost-effectiveness analysis (costs and outcomes) within the framework of the Spanish National Health System was done. The alternatives to tiotropium analyzed were ipratropium and salmeterol. Direct health care costs associated with hospital treatment were calculated. Forced expiratory volume in 1 second, quality of life (with the Saint George's Respiratory Questionnaire), dyspnea transitional index, mean stay in hospital, and exacerbations were the variables used to measure effectiveness. Values for these variables were taken from the main reviews and randomized clinical trials published for tiotropium. RESULTS: For COPD patients, treatment with tiotropium leads to a greater reduction in exacerbations (37% compared to ipratropium and 25% compared to salmeterol 25%), and a reduction in the number of days in hospital (33% compared to ipratropium and 14% compared to salmeterol). Therefore, use of tiotropium could save ;100 000 for the current rates of admission and lengths of hospital stay in Spain. CONCLUSIONS: Tiotropium was more effective than ipratropium and salmeterol as measured by objective clinical variables (forced expiratory volume in 1 second) and subjective ones (the Saint George's Respiratory Questionnaire and dyspnea transitional index). Hospital stays were shorter and exacerbations fewer with tiotropium. In all cases, tiotropium was more cost-effective than the alternatives, thus use of tiotropium could help hospitals to save money.