Efficacy of recombinant activated factor VII vs. activated prothrombin complex concentrate for patients suffering from haemophilia complicated with inhibitors: a Bayesian meta-regression.

The optimal on-demand treatment of joint bleeds in haemophilia patients with inhibitors is a source of debate, with studies reporting various efficacy levels for different drugs and dosage regimens. To analyse, in a unified Bayesian meta-regression model, the published efficacy of recombinant activated factor VII (rFVIIa) and/or activated prothrombin complex concentrate (aPCC) as on-demand treatments for joint bleeds in haemophilia patients with inhibitors. A systematic search was carried out to identify studies reporting on dosage and efficacy of rFVIIa and aPCC in the treatment of joint bleeds in the target patient population. Data were abstracted and included in the model and adjusted for potential sources of heterogeneity. Pooled efficacy levels for typical rFVIIa and aPCC regimens were estimated. Seventeen studies, collectively reporting on >2000 joint bleeds, were included. Medication type combined with dosage was the only significant explanatory parameter. The model predicts that a typical regimen of 90 microg kg(-1) rFVII repeated every 3 h if needed results in cumulative joint bleed resolution of 66%, 88% and 95% after 12, 24 and 36 h, respectively. In comparison, a typical regimen of 75 IU kg(-1) aPCC repeated every 12 h if needed results in cumulative joint bleed resolution of 39%, 62% and 76%, respectively. These differences were statistically significant and were also robust in sensitivity analyses. This analysis suggests that a typical rFVIIa regimen will resolve joint bleeds more effectively than a typical aPCC regimen after 12, 24 and 36 h.

Cost-Effectiveness Analysis of Aripiprazole Augmentation Treatment of Patients with Major Depressive Disorder Compared to Olanzapine and Quetiapine Augmentation in Turkey: A Microsimulation Approach.

OBJECTIVES: Major depressive disorder (MDD) is a chronic illness associated with a major burden on quality of life (QOL) and health care resources. Aripiprazole augmentation to antidepressant treatment was recently approved for patients with MDD responding insufficiently to antidepressant treatment in Turkey. The objective was to estimate the cost-effectiveness of aripiprazole augmentation in this indication compared with olanzapine and quetiapine augmentation from a payer perspective. METHODS: A lifetime economic model was built simulating transitions of patients with MDD between major depressive episodes (MDEs) and remission. During MDEs, patients were treated with adjunctive aripiprazole, quetiapine, or olanzapine. Patients who did not respond switched to subsequent treatment lines. Comparative effectiveness between adjunctive aripiprazole, quetiapine, and olanzapine was estimated by using an indirect comparison. Resource utilization and costs were obtained from Turkish studies. RESULTS: Over a lifetime horizon, patients treated with aripiprazole spent less time in MDEs than did patients treated with quetiapine (-11 weeks) and olanzapine (-7 weeks). On average, patients treated with aripiprazole showed improvement in QOL compared with patients treated with quetiapine (+0.054 quality-adjusted life-years [QALYs]) and olanzapine (+0.039 QALYs) combined with cost saving of 593 Turkish lira (TL) versus quetiapine and 485 TL versus olanzapine. The probability that adjunctive aripiprazole would be cost-effective among the three strategies ranged between 74% and 75% for willingness-to-pay values between 0 TL and 100,000 TL per QALY gained. CONCLUSIONS: This is the first lifetime health-economic model in Turkey that takes patient heterogeneity into account when assessing QOL and costs of different adjunctive strategies in MDD. The results indicate that adjunctive treatment with aripiprazole provides health benefits at lower costs in patients with MDD when compared with quetiapine and olanzapine augmentation.

The cost-effectiveness of paliperidone extended release in Spain.

BACKGROUND: Paliperidone Extended Release OROS (ER) is a new atypical antipsychotic for the treatment of schizophrenia. The objective is, based on a previously published model, to analyze the clinical and economic effects of Paliperidone ER in a Spanish setting compared to olanzapine oral and aripiprazole. METHODS: An existing discrete event simulation model was adapted to reflect the treatment of schizophrenia in Spain in terms of costs, resource use, and treatment patterns. Inputs for the model were derived from clinical trial data, literature research, database analysis and interviews with local clinical experts. The time horizon is 5 years and Spanish discount rate was applied. Outputs include direct medical costs and Quality Adjusted Life-Years (QALYs). Extensive sensitivity analyses were carried out to assess the robustness of the results, using ordinary least squares analysis and cost-effectiveness scatter plots. RESULTS: The results show that the mean incremental QALYs (95% CI) compared to olanzpine is 0.033 [-0.143, 0.304] and compared to aripiprazole 0.029 [-0.107, 0.300]. The corresponding mean incremental costs and corresponding confidence intervals are -€1425 [-€10,247, €3084] and -€759 [-€10,479, €3404], respectively. The probability that paliperidone ER is cost-saving and health gaining compared to olanzapine and aripiprazole is 76% and 72%, respectively. Paliperidone ER was estimated to have 80% and 81% probability of being cost-effective compared to olanzapine at a willingness to pay of €20,000 and €30,000 and 73% and 74% compared to aripiprazole, respectively. LIMITATIONS: Some of the modeled inter-relationships had to be based on expert opinion due to a lack of information. Also, foreign sources for the disutility of adverse events had been used due to a lack of Spanish data. Prolactin-related side-effects, indirect costs, and potential compliance advantages of paliperidone ER were not considered. It is unlikely that these limitations affected the conclusions. CONCLUSION: Based on differences in drug acquisition costs, side-effects, and risk of relapse, the model predicts that, in the Spanish healthcare setting, paliperidone ER dominates oral olanzapine and aripiprazole, with a probability of 76% and 72%, respectively.

Fingolimod reduces direct medical costs compared to natalizumab in patients with relapsing-remitting multiple sclerosis in The Netherlands.

OBJECTIVE: To assess the costs of oral treatment with Gilenya® (fingolimod) compared to intravenous infusion of Tysabri® (natalizumab) in patients with relapsing-remitting multiple sclerosis (RRMS) in The Netherlands. METHODS: A cost-minimization analysis was used to compare both treatments. The following cost categories were distinguished: drug acquisition costs, administration costs, and monitoring costs. Costs were discounted at 4%, and incremental model results were presented over a 1, 2, 5, and 10 year time horizon. The robustness of the results was determined by means of a number of deterministic univariate sensitivity analyses. Additionally, a break-even analysis was carried out to determine at which natalizumab infusion costs a cost-neutral outcome would be obtained. RESULTS: Comparing fingolimod to natalizumab, the model predicted discounted incremental costs of -€2966 (95% CI: -€4209; -€1801), -€6240 (95% CI: -€8800; -€3879), -€15,328 (95% CI: -€21,539; -€9692), and -€28,287 (95% CI: -€39,661; -€17,955) over a 1, 2, 5, and 10-year time horizon, respectively. These predictions were most sensitive to changes in the costs of natalizumab infusion. Changing these costs of €255 within a range from €165-364 per infusion resulted in cost savings varying from €4031 to €8923 after 2 years. The additional break-even analysis showed that infusion costs-including aseptic preparation of the natalizumab solution-needed to be as low as the respective costs of €94 and €80 to obtain a cost neutral result after 2 and 10 years. LIMITATIONS: Neither treatment discontinuation and subsequent re-initiation nor patient compliance were taken into account. As a consequence of the applied cost-minimization technique, only direct medical costs were included. CONCLUSION: The present analysis showed that treatment with fingolimod resulted in considerable cost savings compared to natalizumab: starting at €2966 in the first year, increasing to a total of €28,287 after 10 years per RRMS patient in the Netherlands.