Comparison of COPD health care utilization and associated costs across patients treated with LAMA+LABA fixed-dose therapies.

BACKGROUND: There is limited clinical trial and/or real-world evidence comparing differences among currently approved fixed-dose combination (FDC) long-acting muscarinic antagonist (LAMA)/long-acting beta2-agonist (LABA) treatments. OBJECTIVE: To compare chronic obstructive pulmonary disease (COPD)-related and all-cause health care resource utilization (HCRU) and costs between COPD patients initiating tiotropium (TIO) + olodaterol (OLO) versus (a) other LAMA + LABA FDCs and (b) umeclidinium (UMEC) + vilanterol (VI), specifically. METHODS: In this retrospective observational study, patients initiating fixed-dose LAMA + LABA therapy (earliest fill date = index date) between January 1, 2014, and September 30, 2018, were identified using administrative claims data from the Optum Research Database. Patients were followed post-index for 1-12 months. Follow-up was censored at the earliest occurrence of index therapy discontinuation or switch, health plan disenrollment, study end date, or reaching the maximum 12-month allowed duration. Propensity score matching of 1:2 was used to balance differences in baseline characteristics between cohorts for each of the 2 comparisons. Annualized population averages of HCRU and costs were calculated for each cohort as [sum of visits (or costs) for all individuals during the follow-up period] ÷ [sum of follow-up on-treatment time for all individuals] × 365 days. RESULTS: After matching, compared with patients who initiated other LAMA + LABAs or UMEC + VI, patients who initiated TIO + OLO had 14.29% and 16.95% fewer mean annualized per-patient COPD-related emergency department (ED) visits (vs. other LAMA + LABAs: 0.49 vs. 0.59, P = 0.005; vs. UMEC + VI: 0.48 vs. 0.56, P = 0.026) and 3.07% and 3.14% fewer mean annualized per-patient pharmacy fills (vs. other LAMA + LABAs: 12.66 vs. 13.07, P = 0.016; vs. UMEC + VI: 12.62 vs. 13.02, P = 0.022), leading to 17.39% and 21.47% lower mean annualized per-patient COPD-related ED costs (vs. other LAMA + LABAs: $289 vs. $368, P = 0.003; vs. UMEC + VI: $285 vs. $345, P = 0.027) and 4.56% and 5.67% lower mean annualized per-patient pharmacy spending (vs. other LAMA + LABAs: $3,570 vs. $3,741, P < 0.001; vs. UMEC + VI: $3,556 vs. $3,770, P < 0.001) in the follow-up period. Similarly, patients in the TIO + OLO cohort had 15.63% and 21.17% fewer mean annualized per-patient all-cause ED visits (vs. other LAMA + LABAs: 1.08 vs. 1.37, P < 0.001; vs. UMEC + VI: 1.08 vs. 1.28, P = 0.001), 8.29% fewer mean annualized per-patient outpatient visits (vs. UMEC + VI: 13.28 vs. 14.48, P = 0.031), 3.41% fewer mean annualized per-patient pharmacy fills (vs. other LAMA + LABAs: 56.92 vs. 58.93, P = 0.028), 19.48% and 22.28% lower mean annualized per-patient all-cause ED costs (vs. other LAMA + LABAs: $755 vs. $971, P < 0.001; vs. UMEC + VI: $749 vs. $930, P < 0.001), and 10.86% lower mean annualized per-patient outpatient setting costs (vs. UMEC + VI: $3,348 vs. $3,756, P = 0.050). There were no statistically significant differences for the other outcome measures. CONCLUSIONS: In a real-world setting, differences in HCRU and costs were observed between FDC LAMA + LABAs, with patients initiating TIO + OLO having lower ED visits/costs, COPD-related pharmacy fills/costs, and all-cause pharmacy use and outpatient visits/costs than those initiating other FDC LAMA + LABAs or UMEC + VI specifically. The remaining HCRU and cost measures were not significantly different. DISCLOSURES: This study was sponsored by Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI; Ridgefield, CT). BIPI was given the opportunity to review the manuscript for medical and scientific accuracy, as well as intellectual property considerations. Palli is an employee of BIPI. Xie, Chastek, Elliott, and Bengtson are employees of Optum, which was contracted by BIPI to conduct this study. The authors received no direct compensation related to the development of the manuscript. Part of the results of this study were accepted and presented at the 30th European Respiratory Society (ERS) International Congress (September 7-9, 2020; virtual).

Effect of Age on the Efficacy and Safety of Once-Daily Single-Inhaler Triple-Therapy Fluticasone Furoate/Umeclidinium/Vilanterol in Patients With COPD: A Post Hoc Analysis of the Informing the Pathway of COPD Treatment Trial.

BACKGROUND: In the Informing the Pathway of COPD Treatment (IMPACT) trial, single-inhaler triple-therapy fluticasone furoate (FF), umeclidinium (UMEC), and vilanterol (VI) reduced moderate/severe exacerbation rates vs FF/VI and UMEC/VI in patients with symptomatic COPD and a history of exacerbations, with a similar safety profile. RESEARCH QUESTION: Are trial outcomes with single-inhaler triple-therapy FF/UMEC/VI vs FF/VI and UMEC/VI affected by age in patients with symptomatic COPD and a history of exacerbations? STUDY DESIGN AND METHODS: IMPACT was a phase III, double-blind, 52-week trial. Patients ≥ 40 years of age with symptomatic COPD and ≥ 1 moderate/severe exacerbation in the previous year were randomly assigned 2:2:1 to FF/UMEC/VI 100/62.5/25 µg, FF/VI 100/25 µg, or UMEC/VI 62.5/25 µg. End points assessed by age included annual rate of moderate/severe exacerbations, change from baseline (CFB) in trough FEV1, proportion of St. George's Respiratory Questionnaire (SGRQ) responders (≥ 4 units decrease from baseline in SGRQ total score), and safety. RESULTS: The intention-to-treat population comprised 10,355 patients; 4,724 (46%), 4,225 (41%), and 1,406 (14%) were ≤ 64, 65 to 74, and ≥ 75 years of age, respectively. FF/UMEC/VI reduced on-treatment moderate/severe exacerbation rates vs FF/VI (% reduction [95% CI]: ≤ 64 years, 8% [-1 to 16]; P = .070; 65-74 years, 22% [14-29]; P < .001; ≥ 75 years, 18% [3-31]; P = .021) and vs UMEC/VI (≤ 64 years, 16% [7-25]; P = .002; 65-74 years, 33% [25-41]; P < .001; ≥ 75 years, 24% [6-38]; P = .012), with greatest rate reduction seen in the 65 to 74 and ≥ 75 years subgroups. Post hoc analyses of CFB in trough FEV1 and proportion of SGRQ responders at week 52 were significantly greater with FF/UMEC/VI than with FF/VI or UMEC/VI in all subgroups. No new safety signals were identified. INTERPRETATION: FF/UMEC/VI reduced the rate of moderate/severe exacerbations and improved lung function and health status vs FF/VI and UMEC/VI irrespective of age for most end points, with a similar safety profile. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02164513; URL: www.clinicaltrials.govCTT116855.

Prospective observational study of the use of omeprazole and maropitant citrate in veterinary specialist care.

The proton pump inhibitor omeprazole is administered to dogs with gastroduodenal ulceration or oesophagitis, whereas the neurokinin-1 receptor antagonist maropitant citrate is licensed as an antiemetic drug. In people, omeprazole is overprescribed in hospitals, increasing the risk of adverse effects and imposing unnecessary costs in healthcare. To investigate the use of omeprazole and maropitant in our veterinary specialist hospital, we conducted a prospective observational study in its Medicine and Surgery wards, recording patient data and obtaining contemporaneous information from clinicians about their reasons for administering either drug. In doing so, we find omeprazole and maropitant are administered to a large proportion of dogs, including to many of those with no presenting signs suggestive of gastrointestinal disease. We find prescribing clinicians consider both drugs safe but often underestimate their financial cost. We find the stated reasons and objective predictors of administration of both drugs vary according to clinical setting but that these modalities yield concordant results. Reviewing the manner of administration and stated indications for use of both drugs, we find omeprazole is often administered outside dosing recommendations, and both drugs are frequently administered for aims that are unlikely to be achieved when considering their known biological effects in dogs. In conclusion, our work reveals probable overprescribing of omeprazole and maropitant citrate in hospitalised dogs, highlighting a need for initiatives to decrease inappropriate prescribing.

Cost-Effectiveness Of Once-Daily Single-Inhaler Triple Therapy In COPD: The IMPACT Trial.

Background: We assessed the cost-effectiveness of single-inhaler fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI) versus FF/VI or UMEC/VI from a Canadian public healthcare perspective, incorporating data from the IMPACT trial in chronic obstructive pulmonary disease (COPD) (NCT02164513). Methods: Baseline inputs and treatment effects from IMPACT were populated into the validated GALAXY-COPD disease progression model. Canadian unit costs and drug costs (Canadian dollars [C$], 2017) were applied to healthcare resource utilization and treatments. Future costs and health outcomes were discounted at 1.5% annually. Analyses were probabilistic, and outputs included exacerbation rates, costs, and life years (LYs) and quality-adjusted life years (QALYs) gained. Results: Compared with FF/VI and UMEC/VI over a lifetime horizon, the analyses predicted that treatment with FF/UMEC/VI resulted in fewer moderate and severe exacerbations, more LYs and more QALYs gained, with a small incremental cost. The base-case incremental cost-effectiveness ratio (ICER) per QALY gained was C$18,989 (95% confidence interval [CI]: C$14,665, C$25,753) versus FF/VI and C$13,776 (95% CI: C$9787, C$19,448) versus UMEC/VI. FF/UMEC/VI remained cost-effective versus both FF/VI and UMEC/VI in all sensitivity analyses, including in scenario analyses that considered different intervention and comparator discontinuation rates, and treatment effects for subsequent therapy. Conclusion: Treatment with FF/UMEC/VI was predicted to improve outcomes and be a cost-effective treatment option for patients with symptomatic COPD and a history of exacerbations compared with FF/VI or UMEC/VI, in Canada.

Cost-effectiveness of umeclidinium as add-on to ICS/LABA therapy in COPD: A UK perspective.

INTRODUCTION: The cost-effectiveness of long-acting muscarinic antagonist (LAMA) umeclidinium bromide (UMEC) 62.5 µg as add-on therapy to other maintenance COPD treatments is unknown. METHODS: This analysis assessed the cost-effectiveness of the following in COPD: UMEC + fluticasone furoate/vilanterol 100/25 µg (FF/VI); UMEC + fluticasone propionate/salmeterol 250/50 µg (FP/SAL); and UMEC + several alternative choices of inhaled corticosteroid/long-acting ß2-agonist (ICS/LABA). The model was informed with direct and indirect data from previously published studies, with a UK perspective and a lifetime horizon. Sensitivity analyses were also performed. RESULTS: For the lifetime horizon, compared with FF/VI, FP/SAL and ICS/LABAs, addition of UMEC was associated with incremental costs per quality-adjusted life-years (QALY) of £4050, £7210 and £5780, respectively, and incremental costs per life year gain of £3380, £6020 and £4940. All UMEC-containing regimens resulted in numerically lower exacerbation rates versus comparator regimens over a lifetime horizon. CONCLUSIONS: Addition of UMEC to various ICS/LABA treatments was associated with higher cost than ICS/LABA alone, but was cost-effective in most scenarios.

Cost-effectiveness analysis of umeclidinium bromide/vilanterol 62.5/25 mcg versus tiotropium/olodaterol 5/5 mcg in symptomatic patients with chronic obstructive pulmonary disease: a Spanish National Healthcare System perspective.

BACKGROUND: A head-to-head study demonstrated the superiority of once-daily umeclidinium bromide/vilanterol (UMEC/VI) 62.5/25 mcg on trough forced expiratory volume in 1 s (FEV1) versus once-daily tiotropium/olodaterol (TIO/OLO) 5/5 mcg in symptomatic patients with chronic obstructive pulmonary disease (COPD). This analysis evaluated the cost effectiveness of UMEC/VI versus TIO/OLO from a Spanish National Healthcare System perspective, using data from this study and Spanish literature. METHODS: This analysis was conducted from the perspective of the Spanish National Healthcare System with a 3-year horizon as base case. A disease progression model using a linked risk equation approach was used to estimate disease progression and associated healthcare costs, and quality-adjusted life years (QALYs). The Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study was used to develop the statistical risk equations for clinical endpoints, and costs were calculated using a health state approach (by dyspnea severity). Utilities for QALY calculation were estimated using patient baseline characteristics within a regression fit to Spanish observational data. Treatment effect, expressed as change from baseline in FEV1 was obtained from the head-to-head study and used in the model (UMEC/VI minus TIO/OLO difference: + 52 mL [95% confidence interval: 28, 77]). Baseline patient characteristics were sourced from Spanish literature or the head-to-head study if unavailable. A scenario analysis using only the intent-to-treat (ITT) population from the head-to-head study, and sensitivity analyses (including probabilistic sensitivity analyses), were conducted. Direct healthcare costs (2017 Euro) were obtained from Spanish sources and costs and benefits were discounted at 3% per annum. RESULTS: UMEC/VI was associated with small improvements in QALYs (+ 0.029) over a 3-year time horizon, compared with TIO/OLO, alongside cost savings of €393/patient. The ITT scenario analysis and sensitivity analyses had similar results. All probabilistic simulations resulted in UMEC/VI being less costly and more effective than TIO/OLO. CONCLUSION: UMEC/VI dominated TIO/OLO (more effective and less expensive). These results may aid payers and decision-makers in Spain when making judgements on which long-acting muscarinic antagonist/long-acting ß2-agonist (LAMA/LABA) treatments can be considered cost effective in Spain.

Cost-effectiveness analysis of umeclidinium/vilanterol for the management of patients with moderate to very severe COPD using an economic model.

BACKGROUND: Bronchodilators such as long-acting muscarinic antagonists (LAMAs) and long-acting ß2-agonists (LABAs) are central to the pharmacological management of COPD. Dual bronchodilation with umeclidinium/vilanterol (UMEC/VI; 62.5/25 µg) is a novel LAMA/LABA combination approved for maintenance treatment for patients with COPD. OBJECTIVE: The objective of this study was to assess the cost-effectiveness of maintenance treatment with UMEC/VI compared with tiotropium (TIO) 18 µg, open dual LAMA + LABA treatment, or no long-acting bronchodilator treatment in patients with moderate to very severe COPD. METHODS: A Markov model was developed to estimate the costs and outcomes associated with UMEC/VI treatment in patients with moderate to very severe COPD (GSK study number: HO-13-13411). Clinical efficacy, costs, utilities, and mortality obtained from the published literature were used as the model inputs. Costs are presented in US dollars based on 2015 prices. The model outputs are total costs, drug costs, other medical costs, number of COPD exacerbations, and quality-adjusted life-years (QALYs). Costs and outcomes were discounted at a 3% annual rate. Incremental cost-effectiveness ratios were calculated. One-way and probabilistic sensitivity analyses were conducted to assess the effects of changing parameters on the uncertainty of the results. RESULTS: UMEC/VI treatment for moderate to very severe COPD was associated with lower lifetime medical costs ($82,344) compared with TIO ($88,822), open dual LAMA + LABA treatment ($114,442), and no long-acting bronchodilator ($86,751). Fewer exacerbations were predicted to occur with UMEC/VI treatment compared with no long-acting bronchodilator treatment. UMEC/VI provided an 0.11 and 0.25 increase in QALYs compared with TIO and no long-acting bronchodilator treatment, and as such, dominated these cost-effectiveness analyses. Sensitivity analyses confirmed that the results were robust. CONCLUSION: The results from this model suggest that UMEC/VI treatment would be dominant compared with TIO and no long-acting bronchodilator treatment, and less costly than open dual LAMA + LABA treatment in patients with moderate to very severe COPD.

Economic evaluation of 5-HT3 receptor antagonists in combination with dexamethasone for the prevention of 'overall' nausea and vomiting following highly emetogenic chemotherapy in Chinese adult patients.

Background Two pivotal Phase III trials compared the efficacy of palonosetron, ondansetron and granisetron, combined with dexamethasone, for the prevention of nausea and vomiting following highly emetogenic chemotherapy. However, an economic evaluation of these three regimens in the real-world setting of Chinese adult patients has not been determined. Objectives To estimate, from the perspective of the Chinese healthcare system, which of these frequently used strategies consisting of 0.25 mg palonosetron (0.25P), 16 mg ondansetron (Onda), and 3 mg granisetron (Gran), is the most cost-effective option in patients following highly emetogenic chemotherapy. Methods A Markov decision-analytic model was developed. The health and economic outcomes of the three strategies; 0.25P, Onda, and Gran were investigated. The clinical and utility data were taken from published studies. The cost data were calculated according to current local Chinese practices. Sensitivity analyses were performed to determine the impact of uncertainty regarding the results. Results The base-case analysis showed that the 0.25P strategy yielded maximum health benefits compared with the other two strategies. However, the probabilistic sensitivity analysis demonstrated that the Gran strategy was the most cost-effective approach when the willingness-to-pay threshold was not more than US$22,515/quality-adjusted life year. Moreover, palonosetron is not cost-effective in preventing 'overall' nausea and vomiting following highly emetogenic chemotherapy in Chinese patients. Conclusions Our analysis suggests that, compared with palonosetron and ondansetron, 3 mg granisetron may be a cost-effective treatment option in the current Chinese healthcare setting.

Development and validation of an improved HPLC-MS/MS method for comparative pharmacokinetics of penehyclidine hydrochloride following a single intravenous or intramuscular injection.

Penehyclidine hydrochloride (PHC) is an anticholinergic drug with both antimuscarinic and antinicotinic activity. In order to compare the pharmacokinetics of two administration routes (intravenous injection (i.v.) and intramuscular injection (i.m.)) of PHC, an improved High Performance Liquid Chromatography Tandem Mass Spectrometry (HPLC-MS/MS) bioanalytical method was developed for the quantification of PHC in plasma and urine using verapamil as the internal standard (I.S.). Chromatography was performed using a Thermo Hypersil GOLD column (30mm×2.1mm, 3µm), with a gradient elution of 1‰ formic acid-10mmol/L ammonium acetate and acetonitrile at 0.3mL/min. Detection and quantitation were performed by electrospray ionization (ESI) and multiple reaction monitoring (MRM) in the positive ion mode. The most intense [M+H](+) MRM transition of PHC at m/z 316.2→128.3 was used for PHC quantitation, and the transition at m/z 454.6→303.2 was used to monitor I.S. The lower limit of quantification (LLOQ) was 0.05 ng/mL. The intraday precision was <6.71% and the interday precision was <11.69%. The pharmacokinetic parameters of i.v. and i.m. administration routes were as follows (i.v. vs i.m.): t1/2 15.73 vs 17.24h, Tmax 0.06 vs 0.26h, AUC0-t 69.35 vs 67.90hng/mL, AUC0-inf 78.24 vs 79.67hng/mL, Cmax 37.5 vs 9.1ng/mL, Ae0-24h 22.7 vs 25.21µg. There were no significant differences between parameters t1/2 and AUC (P>0.05), but significant differences were observed in Cmax, Tmax and Ae0-24h between the two administration routes (P<0.05). The mean absolute bioavailability of the i.m. administration route was 98.4% (95% confidence interval, 93.4-103.6%). Safety results showed that PHC appeared to be well tolerated in both i.v. and i.m. administration routes and pharmacokinetic results showed that PHC was nearly completely absorbed via i.m. administration route.

[ASSESSMENT OF EFFICIENCY OF TREATMENT OF OVERACTIVE BLADDER IN ELDERLY PATIENTS].

The effectiveness of overactive bladder treatment with M-cholinoblocker solifenacin (Vesicare) as monotherapy and in combination with α1-andrenoblocker terazosin (Setegis) or bladdrer training in elderly patients was evaluated. The results of 12 weeks treatment in all treatment modality groups were comparable. Use of solifenacin in combination with α1-andrenoblocker in comparison to solifenacin monotherapy resulted in longer symptoms remission.

[Pharmacoeconomic study of using solifenacin for the treatment of urge urinary incontinence in patients with overactive bladder syndrome].

Overactive bladder syndrome (OAB), accompanied by incontinence, is a relatively common disease. Currently, in the Russian Federation, unfortunately, management of patients with OAB includes the recommendations for symptomatic use of incontinence pads without pharmacotherapy. Along with this, the market is represented by a number of drugs that can reduce the occurrence of adverse symptoms associated with OAB syndrome. This study presents the pharmacoeconomic analysis of use of solifenacin for the treatment of patients with the OAB syndrome in Russia. Based on previous clinical studies, formal mathematical model for the development of OAB have been suggested, taking into account the concomitant symptoms (urinary incontinence), and complications (urinary tract infections, skin infections, depression and fractures). The model considers the direct medical and non-medical costs, as well as indirect social costs, arising from the traditional management of patients with OAB syndrome (no medication) and the use of solifenacin. As a result, it was found that the use of solifenacin is economically feasible option for the management of patients with OAB within 1 year, the difference in costs between these strategies per patient is 2,385 rubles. The use of solifenacin ceases to be a resource-saving if the cost of incontinence pads will reduced by more than half of the basic price included in the calculations, or if the effectiveness of solifenacin would be 15% lower than the value used in the basic model.

Cost-effectiveness analysis of solifenacin versus oxybutynin immediate-release in the treatment of patients with overactive bladder in the United Kingdom.

OBJECTIVE: To carry out a cost-utility analysis comparing initial treatment with solifenacin 5 mg/day vs oxybutynin immediate-release (IR) 15 mg/day for the treatment of patients with overactive bladder (OAB) from the perspective of the U.K. National Health Service (NHS). METHODS: A Markov model with six health states was developed to follow a cohort of OAB patients treated with either solifenacin or oxybutynin during a 1-year period. Costs and utilities were accumulated as patients transited through the health states in the model and a drop-out state. Some of the solifenacin patients were titrated from 5 mg to 10 mg/day at 8 weeks. A proportion of drop-out patients were assumed to continue treatment with tolterodine ER. Utility values were obtained from a Swedish study and pad use was based on a multinational clinical trial. Adherence rates for individual treatments were derived from a U.K. database study. For pad use and utility values, the drop-out state was split between those patients who were no longer receiving treatment and those on second-line therapy. Patients on second-line therapy who drop-out were referred for a specialist visit. Results were expressed in terms of incremental cost-utility ratios. RESULTS: Total annual costs for solifenacin and oxybutynin were £504.30 and £364.19, respectively. First-line drug use represents 49% and 4% of costs and pad use represent 23% and 40% of costs for solifenacin and oxybutynin, respectively. Differences between cumulative utilities were small but were greater for solifenacin (0.7020 vs. 0.6907). The baseline incremental cost-effectiveness ratio was £12,309/QALY. CONCLUSION: Under the baseline assumptions, solifenacin would appear to be cost-effective with an incremental cost-utility of less than £20,000/QALY. However, small differences in utility between the alternatives and the large number of drop-outs means that the results are sensitive to small adjustments in the values of utilities assigned to the drop-out state.

Initial assessment of single and repeat doses of inhaled umeclidinium in patients with chronic obstructive pulmonary disease: two randomised studies.

To characterise the safety, tolerability, pharmacodynamics (bronchodilatory effect) and pharmacokinetics of inhaled umeclidinium in patients with chronic obstructive pulmonary disease (COPD). The first investigation was a single dose, randomised, double-blind, placebo-controlled study (clinicaltrials.gov: NCT00515502) in which ipratropium bromide-sensitive patients received umeclidinium (250µg, 500µg, and 1000µg), tiotropium bromide 18µg or placebo. Patients were randomised to receive four out of five possible treatments as an incomplete block four-way cross-over. A subsequent study (clinicaltrials.gov: NCT700732472) was focused on assessment of safety, tolerability and pharmacokinetics of umeclidinium (250µg and 1000µg) administered once-daily for 7 days in a randomised, double-blind, placebo-controlled, parallel-group design. Of the 24 patients randomised for the single dose study, 20 completed; 31 out of 38 patients completed the repeat dose study. Most adverse events were mild-to-moderate and transient. Examination of heart rate, QTc interval, blood pressure and clinical laboratory assessments raised no concern over the safety of umeclidinium. Evidence of pharmacology was demonstrated in first study by statistically significant increases in specific airway conductance (sGaw) for up to 24h for all active treatments compared with placebo. Increases in forced expiratory volume in 1s were also observed. Pharmacokinetic analysis demonstrated that maximum observed plasma umeclidinium concentration (Cmax) was reached rapidly (time to Cmax: ∼5-15min) after single and repeat doses; 1.5-1.9-fold accumulation was observed after repeat-dosing. Single and repeat doses of umeclidinium were well tolerated and produced clinically relevant lung function improvements over 24h in patients with COPD.

Canadian cost-effectiveness analysis of solifenacin compared to oxybutynin immediate-release in patients with overactive bladder.

OBJECTIVE: To estimate the cost effectiveness of solifenacin 5 mg/day compared to oxybutynin immediate-release (IR) 15 mg/day in patients with overactive bladder, from the perspective of the Canadian healthcare (payer) system. RESEARCH DESIGN AND METHODS: A Markov model was adapted to estimate the incremental cost per quality-adjusted life-year (QALY) of solifenacin and oxybutynin IR over a 1-year time horizon, based on efficacy and discontinuation data from the Canadian VECTOR (VEsicare in Comparison To Oxybutynin for oveRactive bladder patients) study. In the model, patients who discontinued treatment were offered tolterodine extended release 4 mg/day as second-line. Model robustness was tested using various sensitivity analyses. Utility values were derived from published literature; incontinence pads were included in a secondary analysis. RESULTS: In the base-case analysis, total costs over 1 year were CAN$695 and CAN$550 in the solifenacin and oxybutynin IR groups, respectively. When including incontinence pad costs, there was an incremental saving of CAN$1,831 per patient with solifenacin. Solifenacin was associated with an incremental QALY gain of 0.01 over 1 year. In the base-case analysis without incontinence pads, the incremental cost-utility ratio for solifenacin was CAN$14,092. Probabilistic analyses showed no overlap in the 95% confidence intervals for total costs or QALYs with or without incontinence pads. Solifenacin was cost effective in >90% of cases, based on a willingness-to-pay threshold of CAN$50,000 per additional QALY, irrespective of whether pad costs were included in the model. The most influential variables were the discontinuation rates and the cost of incontinence pads. Limitations of the analysis relate mainly to the fact that data in the VECTOR study were collected using a direct questioning approach, which might have increased the reporting of dry mouth. CONCLUSIONS: Solifenacin 5 mg/day was a cost-effective treatment compared with oxybutynin IR 15 mg/day. TRIAL REGISTRATION: NCT00431041 (of the VECTOR study, upon which the analysis in this paper was based).

Cost-effectiveness analysis of solifenacin flexible dosing in patients with overactive bladder symptoms in four Nordic countries.

OBJECTIVE: The purpose of the present analysis was to analyze and compare the cost-effectiveness of solifenacin flexible dosing (5-10 mg) with tolterodine 4 mg sustained release (SR) or placebo (assumed to be comparable to no treatment) for patients with overactive bladder (OAB) symptoms. DESIGN: A decision-analytic model was constructed. METHODS: Costs and effects were evaluated for the three treatment options in a one-year timeframe. Costs included were treatment costs, cost of pad use, and patients productivity loss based on data from the Nordic countries. SAMPLE: Results from two randomized controlled trials were used as input data in the cost-effectiveness analysis. MAIN OUTCOME MEASURES: Quality adjusted life years and incremental cost-effectiveness ratio. RESULTS: Solifenacin flexible dosing was more effective with respect to reducing OAB symptoms compared to both placebo and tolterodine 4 mg. Treatment with both solifenacin and tolterodine was more costly compared to placebo, but treatment with solifenacin was a less costly alternative compared to tolterodine 4 mg SR. Sensitivity analyses revealed that the conclusions were robust. CONCLUSION: Solifenacin flexible dosing was a cost-effective treatment alternative compared to tolterodine 4 mg SR.

Impact of solifenacin on resource utilization, work productivity and health utility in overactive bladder patients switching from tolterodine ER.

OBJECTIVE: Assess changes in resource utilization, work and activity impairment, and health utility among OAB patients continuing to have urgency symptoms with tolterodine ER 4 mg and willing to try solifenacin 5/10 mg. RESEARCH DESIGN AND METHODS: This was an open-label, non-comparative, flexible-dosing, multicenter, 12-week study assessing the efficacy and safety of solifenacin 5/10 mg/day. Patients receiving tolterodine ER 4 mg/day for >/=4 weeks but continuing to experience residual urgency symptoms (>/=3 urgency episodes/24 h) were enrolled into the study. After a 14-day washout, patients began treatment with solifenacin 5 mg/day with dosing adjustments allowed at Weeks 4 and 8. MAIN OUTCOME MEASURES: Outcomes were assessed using the Work Productivity and Activity Impairment Questionnaire - Specific Health Problem (WPAI-SHP), Health Utilities Index (HUI), and a resource utilization questionnaire administered at Pre-Washout and Week 12. RESULTS: Patients (n=440) reported significantly fewer physician office visits (p<0.0001), UTIs (p<0.0001), and pads/diapers (p=0.0009) during the study period while receiving solifenacin 5/10 mg/day, compared with the Pre-Washout period when receiving tolterodine ER 4 mg/day. After 12 weeks of treatment with solifenacin 5/10 mg/day, patients reported a reduction in work time missed (p=0.0017), less impairment while working (p<0.0001), less overall work impairment (p<0.0001) and a reduction in activity impairment (p<0.0001) compared to Pre-Washout. There was no significant difference in health utility scores. Treatment-emergent adverse events were mostly anticholinergic in nature, and were mild to moderate in severity. CONCLUSION: Overall, solifenacin 5/10 mg/day improved work productivity, activity participation, and reduced medical care use in OAB patients who continued to have urgency symptoms with tolterodine ER 4 mg/day and wished to switch to solifenacin 5/10 mg. This was an open-label, non-comparative study; therefore, further research is needed to confirm these results.

[Assessment of symptoms severity in patients with overactive bladder].

Symptoms severity was assessed in 533 patients with urinary bladder overactivity (mean age 56.4 +/- 0.6 years). All the patients kept urination diary for 3 days, some patients filled in KHQ questionnaire to find out quality of life, were examined urodynamically. Overactive bladder (OAB) symptoms were studied in 52 patients before and after 12 weeks of solifenacin treatment in a dose 5 mg/day. The statistical analysis identified three degrees of OAB symptoms. The severity was calculated according to the formula in points (S): S = 2 x number of urinations for 3 days + number of urges for 3 days + 1*(*--in the presence of urgent urine incontinence). In 62 points and less the diagnosis was "mild severity" of the symptoms (degree 1), in 63-80 points--"moderate severity" (degree 2), in 80 points and more--"great severity" (degree 3). Of 533 patients, 119 (22.3%) had symptoms of degree 1, 148 (27.8%)--of degree 2, 266 (49.9%)--of degree 3. The patients with more severe disease had more distinct changes in urodynamic indices and worse quality of life. Solifenacin treatment reduced severity of the symptoms in most patients treated. Before solifenacin administration degrees 1, 2 and 3 of the symptoms severity were detected in 12 (23.1%), 13 (25.0%) and 27 (51.9%) patients, respectively. After treatment--in 26 (50.0%), 16 (30.8%) and 6 (11.5%) patients, respectively. OAB symptoms were absent in 4 (7.7%) patients. Thus, it is shown that the proposed system of the system assessment reflects severity of OAB clinical symptoms, the degree of urodynamic disorders and deterioration of quality of life. This classification system can be used for follow-up assessment of OAB symptoms in the treatment process. It is simple and perspective for wide application.

Assessment of the use of sialogogues in the clinical management of patients with xerostomia.

This study was conducted to assess the clinical efficacy and adverse effects of pilocarpine, bethanechol and cevimeline in patients with xerostomia. In this open-label crossover assessment in 20 patients with xerostomia, a one- to two-week course of each medication with a one-week washout period was prescribed. Side effects, symptoms, whole stimulated and unstimulated saliva were measured. Each sialogogue was found to increase saliva and decrease symptoms. A mixed-effects analysis showed a greater increase in stimulated saliva on bethanechol compared to pilocarpine (0.106, p = 0.0272). Increased sweating was the most common side effect, experienced more frequently with pilocarpine as compared to bethanechol (p = 0.0588) or cevimeline (p = 0.0143). A carryover effect beyond the washout period was seen. Effects on saliva and side effects vary between sialogogues, suggesting a benefit of trials with different sialogogues to determine individual patient preference. The observed carryover effect suggests that intermittent treatment may be an alternative to continuous treatment with sialogogues.