Economic evaluation of aclidinium bromide in the management of moderate to severe COPD: an analysis over 5 years.

PURPOSE: Aclidinium bromide is a long-acting muscarinic antagonistic used in maintenance treatment of chronic obstructive pulmonary disease (COPD). A model-based health economic study evaluated the cost-effectiveness of aclidinium 400 µg bid as an alternative to tiotropium 18 µg od for this indication in the US. PATIENTS AND METHODS: PATIENT CHARACTERISTICS IN THIS MODEL REFLECT THOSE IN THE ACLIDINIUM CLINICAL STUDIES: age >40 years, stable moderate-to-severe COPD, current or ex-smokers (>10 pack-years), post-salbutamol forced expiratory volume in 1 second (FEV1) ≥30% and <80% of predicted normal value, and FEV1/forced vital capacity <70%. The model consists of five main health states indicating severity of COPD and the level of utility, resource use, and costs. Treatment efficacy over 5 years was modeled using FEV1% predicted; a network meta-analysis comparing aclidinium and tiotropium was used to estimate disease progression during the first 24 weeks, and results from the UPLIFT trial were used for time points after 24 weeks. Quality of life was assessed using utility scores in US patients from the UPLIFT trial. Cost-effectiveness was assessed as the incremental cost per quality-adjusted life year (QALY) gained. RESULTS: Over 5 years, QALYs were 3.50 for aclidinium versus 3.49 for tiotropium; life years accumulated were 4.52 for both. In this economic model, aclidinium versus tiotropium showed marginally fewer exacerbations (3.364 versus 3.390, respectively) and mean total health care costs (US$126,274 versus US$128,591, respectively). In all scenario analyses performed (discount factors of 0% and 6% for benefits and costs; time horizon of 1 year; mapping St George's Respiratory Questionnaire to European Quality of Life-5 Dimensions; excluding pharmacy costs, COPD-related cost only; cost of exacerbations; including ACCORD II trial in the network meta-analysis), aclidinium was associated with lower costs and marginally greater QALYs versus tiotropium. CONCLUSION: Aclidinium is potentially cost-effective compared with tiotropium for maintenance treatment of moderate-to-severe COPD.

A network meta-analysis of the efficacy of opioid analgesics for the management of breakthrough cancer pain episodes.

CONTEXT: With many medications available for the management of breakthrough cancer pain (BTCP), physicians may require additional guidance in selecting an appropriate medication to suit an individual patient's needs. OBJECTIVES: To identify all the evidence and assess the relative clinical value of currently approved BTCP medications. METHODS: Following a systematic literature search (2007-2010), the results of 10 randomized controlled trials investigating the effects of BTCP medications (intranasal fentanyl spray [INFS], fentanyl pectin nasal spray, fentanyl sublingual tablets, fentanyl buccal soluble film, fentanyl buccal tablets, oral transmucosal fentanyl citrate, and morphine sulfate immediate release) were synthesized using a network meta-analysis. The main outcome was pain intensity difference (PID) relative to placebo up to 60 minutes after the intake of medication. RESULTS: INFS, fentanyl pectin nasal spray, fentanyl buccal tablet, and oral transmucosal fentanyl citrate showed greater PIDs relative to placebo than other BTCP medications 15 minutes after intake. All other medications showed greater PIDs relative to placebo at 30 minutes, except morphine sulfate immediate release, which did not show efficacy over placebo until 45 minutes. Only INFS produced clinically meaningful pain relief (absolute PID ≥2) at 15 minutes. CONCLUSION: From current evidence, although all BTCP medications provided pain relief within the time frames assessed, transmucosal fentanyl medications achieved a greater level of pain relief in a shorter time frame than placebo or oral morphine.

Relative efficacy of bivalirudin versus heparin monotherapy in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention: a network meta-analysis.

In the absence of head-to-head clinical data, the objective of this study was to indirectly compare the efficacy and safety of a bivalirudin-based anticoagulation strategy with that of heparin monotherapy in patients with ST-elevation myocardial infarction (STEMI) intended for primary percutaneous coronary intervention. A systematic literature review was performed to identify randomized controlled trials to build a network of bivalirudin and heparin monotherapy strategies in STEMI patients using heparin, with glycoprotein IIb/IIIa inhibitor as a common reference strategy. At 30 days, the bivalirudin-based strategy was expected to result in lower mortality rates than heparin monotherapy (odds ratio [OR], 0.55; credible limit [CrL], 0.32-0.95). This relationship was sustained at 1 year. At 30 days, the risk for stroke (OR, 0.88; CrL, 0.37-2.13), myocardial infarction (OR, 0.79; CrL, 0.40-1.55), and thrombolysis in myocardial infarction major and minor bleedings (OR, 0.66; CrL, 0.45-0.98) tended to be numerically reduced with bivalirudin in comparison with heparin monotherapy. For patients with STEMI intended for primary percutaneous coronary intervention, bivalirudin is associated with lower mortality rates in comparison with heparin monotherapy. This study suggests that bivalirudin is more effective and safer than heparin monotherapy and should therefore be preferred over heparin monotherapy.

The time consuming nature of phenylketonuria: a cross-sectional study investigating time burden and costs of phenylketonuria in the Netherlands.

BACKGROUND: Phenylketonuria (PKU) is a rare inborn error of metabolism that affects the ability of patients to metabolise phenylalanine (Phe). Lifelong management of blood Phe levels is required in order to avoid the complications associated with PKU. This constitutes a severely protein restricted diet, and regular monitoring of Phe levels. Management of PKU may be costly and time-consuming for adult patients or caregivers of PKU-affected children. A cross-sectional study was performed with patients or their caregivers in the Netherlands to gain insight into the personal time burden and cost of living with PKU. METHODS: A systematic literature review was performed to identify all aspects of PKU management that may pose a financial or time burden on patients or caregivers. Findings were confirmed through interviews with PKU experts and feedback from patients and caregivers, and consolidated into a questionnaire that aimed to evaluate the impact of each of these factors. Early and continuously treated adult patients and caregivers from seven metabolic centres were recruited to complete the questionnaire online. RESULTS: 22 adult patients and 24 caregivers participated in the study. Managing a Phe-restricted diet represented an extra time burden of 1 h and 24 min for caregivers and 30 min for adult patients per day. Caregivers reported a significantly higher time burden than adult patients. The median total out-of-pocket cost (OOPC) for patients was €604 annually, with 99% of expenditure on low-protein food products. Greater disease severity was significantly associated with increased OOPC and time burden for both adult patients and caregivers. CONCLUSIONS: Management of PKU is associated with a considerable time burden for both caregivers of children with PKU and adult patients. Caregivers of PKU-affected children reported a significantly higher time burden than adult patients. The OOPC of caregivers and patients was mainly driven by the expenditure on low protein food.

Indirect treatment comparison of abatacept with methotrexate versus other biologic agents for active rheumatoid arthritis despite methotrexate therapy in the United kingdom.

OBJECTIVE: To compare the efficacy of abatacept and alternative biologic disease-modifying antirheumatic drugs (DMARD) in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX) in the United Kingdom. METHODS: A systematic literature search identified 11 individual studies investigating the efficacy of abatacept, infliximab, adalimumab, etanercept, certolizumab pegol, and golimumab in adult patients with RA that did not respond to MTX. The clinical trials included in this analysis were similar in trial design, baseline patient characteristics, and background therapy (i.e., MTX). The key clinical endpoints of interest were the Health Assessment Questionnaire (HAQ) change from baseline (CFB) and the American College of Rheumatology (ACR) responses at 6 months (24-28 weeks). Results were analyzed using Bayesian network metaanalysis methods, and were expressed as differences in HAQ CFB and ACR20/50/70 relative risks, with 95% credible limits (CrL). RESULTS: Analysis of HAQ CFB at 6 months showed that abatacept is more efficacious than placebo [mean difference in HAQ CFB: -0.30 (95% CrL -0.42; -0.16)] and comparable to all other biologic agents, in patients receiving MTX as background treatment. Abatacept is also expected to result in a higher proportion of ACR responders compared to placebo, with relative risks ranging from 1.90 (95% CrL 1.24; 2.57) for ACR20 to 3.72 (95% CrL 1.50; 10.52) for ACR70, and to result in comparable proportions of ACR responders as other biologic agents, at 6 months. CONCLUSION: Abatacept is expected to result in improvement in functional status comparable to other recommended biologic agents in patients with RA who are unresponsive to MTX in the UK.