Health-related quality of life in pediatric patients with partial onset seizures or primary generalized tonic-clonic seizures receiving adjunctive perampanel.

RATIONALE: Study 311 (E2007-G000-311; NCT02849626) was a Phase 3, multicenter, open-label single-arm study of adjunctive perampanel oral suspension in pediatric patients (aged 4 to <12 years) with partial-onset seizures (POS) (with/without secondarily generalized tonic-clonic seizures [SGTCS]) or primary generalized tonic-clonic seizures (PGTCS). Health-related quality of life (HRQoL) was an exploratory endpoint initially analyzed through simple descriptive summaries. The aim of this post hoc analysis was to provide a more thorough assessment of HRQoL. METHODS: This analysis focused on EQ-5D-Y data collected at Baseline, Week 23, and Week 52. Individual dimensions, visual analog scale (VAS) and summed misery index (MI) were evaluated at all visits and compared by seizure type (POS versus SGTCS versus PGTCS), age (4 to <7 versus 7 to <12), and use of concomitant enzyme-inducing antiepileptic drugs (EIAEDs) (yes versus no). Paretian Classification of Health Change (PCHC) analysis summarized the proportion of patients who showed improvement or deterioration in HRQoL. Waterfall plots assessed changes in EQ-5D-Y scores by treatment-emergent adverse events (TEAEs) and by reduction in seizure frequency. Health state utility values associated with differing seizure frequency states were estimated using a linear mixed model. RESULTS: One hundred and fifteen patients completed EQ-5D-Y at relevant study visits (Seizure type: POS n = 84 [of which 21 had SGTCS], PGTCS n = 31; Age: 4 to <7 years n = 30, 7 to <12 years n = 85; Concomitant EIAEDs: Yes n = 35, No n = 80). Completion rates out of those expected to complete EQ-5D-Y were high at both timepoints (84.4% at Week 23 and 97.2% at Week 52). Overall, VAS/MI remained stable over time (did not exceed minimal important difference); this was similar according to seizure type, age, and EIAED usage. In patients with 'no problems' on any EQ-5D-Y dimension at Baseline, nearly all retained their full health at Week 23 (94.7%), and all retained it at Week 52 (100.0%). PCHC analysis showed fewer patients with POS experienced deterioration in EQ-5D-Y than patients with PGTCS at Week 23 (24.1% versus 42.1%). Not experiencing a TEAE, or remaining seizure-free, was associated with improvements in VAS score at Week 23 compared to those experiencing TEAEs or seizures, respectively. Health state utility values (HSUVs) were estimated as follows: seizure free (LS Mean 0.914 [95% CIs 0.587, 1.240]), ≥1 seizure per year (0.620 [0.506, 0.734]), ≥1 seizure per month (0.596 [0.338, 0.855]), ≥1 seizure per week (0.284 [-0.014, 0.582]). CONCLUSIONS: An in-depth analysis of EQ-5D-Y data allowed for a more nuanced exploration of HRQoL than previous descriptive summaries. Our findings provide evidence that perampanel as adjunctive therapy did not result in deterioration of patient HRQoL. The association between TEAEs or remaining seizure-free and HRQoL warrants further exploration. Increasing seizure frequency was associated with decreasing HSUVs; these can inform cost-effectiveness modeling of perampanel and other therapies aiming to reduce seizure frequency in pediatric patients.

Treatment Options for Dementia with Lewy Bodies: A Network Meta-Analysis of Randomised Control Trials.

INTRODUCTION: Dementia with Lewy bodies (DLB) is the third most common type of dementia after Alzheimer's disease (AD) and vascular dementia. Treatment is targeted at specific disease manifestations/symptoms. While donepezil is approved for the treatment of DLB in Japan, to date no other treatment has been approved for this indication anywhere in the world. Notwithstanding, many of the medications that are approved for AD are widely used in the treatment of DLB with varying degrees of success. Consequently, clinical evidence is limited, and there is a need to understand the comparative efficacy and safety of currently used therapies for DLB. The aim of this study was to conduct a network meta-analysis (NMA) to evaluate the outcomes of the available treatment options based on currently used trial endpoints. METHODS: Using data from a previously published systematic review, we conducted an NMA to investigate the efficacy and safety of treatments in patients with DLB. Networks were based on change from baseline of efficacy endpoints (Mini-Mental State Examination; Neuropsychiatric Inventory; Unified Parkinson's Disease Rating Scale) and rate of safety events (overall adverse events [AEs]; discontinuations; discontinuations due to AEs; psychiatric events). RESULTS: Focused around a common treatment option of placebo, the NMA comprised studies on donepezil, rivastigmine, memantine and quetiapine. Donepezil 3 mg, 5 mg and 10 mg doses were compared against each other and placebo. Overall, donepezil consistently performed better than the alternative treatments when compared to placebo for all efficacy and safety endpoints. However, the small sample size and/or heterogeneity of the studies led to uncertainty, resulting in no statistically significant differences favouring any treatment above another or placebo. CONCLUSION: Despite the lack of statistical significance, when assessing the efficacy and safety outcomes for each drug in the evidence network, donepezil appeared to have a more favourable overall benefit/risk profile for patients with DLB. Further comparative trials are required to improve understanding of the true difference between existing and potential future treatment options.

Economic evaluation of posaconazole versus standard azole therapy as prophylaxis against invasive fungal infections in patients with prolonged neutropenia in Canada.

INTRODUCTION: Posaconazole prophylaxis in high-risk neutropenic patients prevents invasive fungal infection (IFI). An economic model was used to assess the cost effectiveness of posaconazole from a Canadian health care system perspective. METHODS: A decision-analytic model was developed based on data from a randomized trial comparing posaconazole with standard azole (fluconazole or itraconazole) therapy. The model was extrapolated to a lifetime horizon using one-month Markov cycles; lifetime survival was specific to the underlying disease. Drug and treatment costs associated with IFI were estimated using published literature. The model was used to estimate total costs, IFIs avoided, life-years gained and the incremental cost-effectiveness ratio of posaconazole versus standard azole therapy, in 2007 Canadian dollars. RESULTS: Based on the clinical trial data, posaconazole was associated with fewer cases of IFI (0.05 versus 0.11; P=0.003), increased life-years (2.52 years versus 2.43 years) and slightly lower costs ($6,601 versus $7,045) per patient relative to standard azole therapy over a lifetime horizon. Higher acquisition costs for posaconazole were offset by IFI-associated inpatient costs for those prophylaxed with standard azoles. Probabilistic sensitivity analysis indicated a 59% probability that posaconazole was cost-saving versus standard azole therapy and a 96% probability that the incremental cost-effectiveness ratio for posaconazole was at or below the $50,000 per life-year saved threshold. DISCUSSION: In Canada, posaconazole appears to be cost-saving relative to standard azole therapy in IFI prevention among high-risk neutropenic patients.

INTRODUCTION: La prophylaxie au posaconazole chez les patients neutropéniques à haut risque prévient l'infection fongique invasive (IFI). Les chercheurs ont utilisé un modèle économique pour évaluer le rapport coût-efficacité du posaconazole dans un système de santé canadien. MÉTHODOLOGIE: Les chercheurs ont mis au point un modèle de décision analytique fondé sur des données tirées d'un essai aléatoire comparant le posaconazole à un traitement standard à l'azole (fluconazole ou itraconazole). Ils ont extrapolé le modèle à l'horizon d'une vie au moyen de modèles de Markov sur un mois. La survie longitudinale dépendait de la maladie sous-jacente. Ils ont estimé les coûts des médicaments et des traitements associés à l'IFI d'après des publications scientifiques et utilisé le modèle pour estimer les coûts totaux, les IFI évitées, les années de vie gagnées et le rapport coût-efficacité incrémentiel (RCEI) du posaconazole par rapport à une thérapie standard à l'azole, en dollars canadiens de 2007. RÉSULTATS: D'après les données d'essai clinique, le posaconazole s'associait à un moins grand nombre de cas d'IFI (0,05 par rapport à 0,11; P=0,003), à l'augmentation des années de vie (2,52 ans par rapport à 2,43 ans) et à des coûts légèrement moins élevés (6 601 $ par rapport à 7 045 $) par patient par rapport à la thérapie standard à l'azole sur l'horizon d'une vie. Les coûts d'acquisition plus élevés du posaconazole étaient contrebalancés par les coûts d'hospitalisation des patients en raison d'une IFI qui recevaient une prophylaxie standard aux azoles. D'après l'analyse de sensibilité probabiliste, il y avait 59 % de probabilité que le posaconazole soit plus économique que la thérapie standard à l'azole et 96 % de probabilité que le RCEI du posaconazole corresponde ou soit inférieur au seuil de 50 000 $ par année de vie épargnée. EXPOSÉ: Au Canada, le posaconazole semble être économique par rapport à la thérapie standard à l'azole pour prévenir l'IFI chez les patients neutropéniques à haut risque.

Cost effectiveness of the sirolimus-eluting stent in high-risk patients in Canada: an analysis from the C-SIRIUS trial.

BACKGROUND: The cost effectiveness of drug-eluting stents in Canada is debated and deserves further evaluation in high-risk patients. METHODS: We performed an economic analysis from the third-party payer perspective based on the clinical results and resource-utilization data of the C-SIRIUS (The Canadian Study of the Sirolimus-Eluting Stent in the Treatment of Patients with Long De Novo Lesions in Small Native Coronary Arteries) trial, which examined the safety and efficacy of sirolimus-eluting stents (SES) versus bare metal stents (BMS) in high-risk patients with single long de novo lesions in small coronary arteries. Only inpatient costs were considered, including physician fees. We postulated that the incremental cost required to avoid a repeat revascularization (RR) procedure with BMS versus simple balloon angioplasty (BA) could be considered the willingness to pay (WTP) to avoid restenosis in Canada. We assessed the incremental cost-effectiveness ratio (ICER) of SES compared with BMS in these high-risk patients compared with WTP. Results are expressed in 2003 Canadian dollars. RESULTS: With a 7% absolute reduction in the need for RR compared with BA, BMS are associated on average with an ICER of US dollars 12,551/RR avoided (RRA) in Canada. In C-SIRIUS, SES further reduced the need for RR at 1 year from 22% to 4% (p = 0.015) compared with BMS. With a 1.5 stent-to-lesion (STL) ratio and an SES retail price of US dollars 2,700 compared with US dollars 700 for BMS, the ICER of SES versus BMS was US dollars 11,275/RRA -- borderline cost effective compared with the implicit WTP of US dollars 12,551 for such health benefit in Canada. Using a lower STL ratio (1.2) would improve the ICER to US dollars 7941/RRA. CONCLUSIONS: Treatment of long lesions in small vessels with SES increases net healthcare costs. However, the ICER for SES compares favorably with the currently accepted comparator, i.e. BMS, to reduce coronary restenosis -- at least for higher risk patients undergoing single-vessel revascularization.