Objective: Head-to-head randomized controlled trials (RCTs) are the gold standard for assessing comparative treatment effects. In the absence of direct comparisons between all possible antiepileptic drugs (AEDs), however, clinical decision-making in focal (partial onset) epilepsy relies on alternative evidence borne from indirect comparisons including network meta-analyses (NMAs) and from real-world evidence (RWE) studies. We review NMAs and observational RWE studies comparing AEDs in the adjunctive setting to compare the robustness of these methods and to formulate recommendations for future evidence development. Methods: A literature review identified NMAs and RWE studies comparing AEDs for the adjunctive treatment of focal seizures published between January 2008 and October 2018. NMAs were evaluated for robustness using a framework based on guidelines from the National Institute for Health and Care Excellence Decision Support Unit and the International Society for Pharmacoeconomics and OutcomesResearch. RWE studies were evaluated using the GRACE checklist. Results: From a total of 1993 records, 11 NMAs and six RWE studies were eligible. Key limitations identified in the NMAs include nonsystematic selection of RCTs, unexplored heterogeneity between included RCTs in terms of study and patient characteristics, and selection of AEDs and AED doses or dosing strategies that are not reflective of clinical practice. The main limitations of RWE studies concern sample size, design, and analysis methods. Approximately 90% of comparisons between individual AEDs were nonsignificant in the NMAs. None of the RWE studies adjusted for baseline differences between comparator groups; therefore, they lack the validity to make comparative conclusions. Significance: Current NMAs and RWE studies provide only nominal comparative evidence for AED treatments in focal epilepsy, and should be used with caution for decision-making due to their methodological limitations. To overcome these hurdles, adherence to methodological guidelines and concerted efforts to collect relevant outcome data in the real world are needed. |

BackgroundSome antiepileptic drugs (AEDs) induce expression of hepatic enzymes. This can contribute to comorbidities via interference with metabolic pathways and concomitant drug metabolization, thereby increasing the likelihood of health care interventions. Using medical records, we compared the direct health care cost in patients initiating epilepsy therapy with enzyme-inducing AEDs (EIAEDs) vs non-enzyme-active AEDs (nEAAEDs) over up to 12 years.MethodsPatients with untreated epilepsy were indexed in the UK Clinical Practice Research Datalink and Hospital Episode Statistics database when prescribed a new EIAED or nEAAED between January 2001 and December 2010. Propensity score matching reduced confounding factors between cohorts. Patients were followed until cohort treatment failure or data cut-off. The primary outcome was the median standardized monthly direct health care cost during follow-up in 2014 £GBP, calculated using published reference costs and compared using a Mann–Whitney U test.ResultsThe unmatched EIAED cohort (n = 2752) was older (54 vs 46 years), more likely to be male, had more comorbidities, and higher health care resource use/cost during the 1-year pre-index period (median £3014 vs £2516) than the nEAAED cohort (n = 2,137). The most common index EIAED and nEAAED were carbamazepine (63.3%) and lamotrigine (58.0%), respectively. After matching, cohorts had similar features (n = 951 each). Over up to 12 years of follow-up, the median standardized monthly direct health care cost was £229 for the EIAED and £188 for the nEAAED cohorts (p = 0.0091). The median cost was higher for the EIAED cohort in every year of follow-up. In the two cohorts, 25.1% and 20.1% of total mean cost during follow-up was epilepsy-related, with approximately 4.6% and 3.0% for AED acquisition, respectively. The median time to cohort treatment failure was shorter in the matched EIAED cohort (468 vs 1194 days).ConclusionsPatients in the UK who initiated epilepsy therapy with an EIAED appeared to be at higher risk of complications associated with enzyme induction. In long-term matched cohort analyses, the median total direct health care cost associated with EIAED therapy was higher than with nEAAEDs. Changing current treatment practices could potentially improve patient outcomes and reduce costs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12883-017-0837-y) contains supplementary material, which is available to authorized users.

Embase, Scielo and LILACS using the key words "multiple sclerosis" and "esclerosis múltiple" plus "Latin America" and all country names. Full articles or abstracts from meetings reporting original research on cost or economic analyses, budget impact or resource utilization were obtained. No restrictions were placed on publication date or language. All work was done in duplicate by two independent reviewers with adjudication by consensus discussion. Results: We identified 1482 papers, of which 27 were considered for analysis. There were 7 economic analyses (5 costeffectiveness, 2 cost-utility), 5 budget impact analyses, 10 cost analyses (6 drug expenditures and 4 cost of illness), 4 on resource utilization and 1 on productivity loss. Studies were obtained from 5 countries (18 Brazil, 3 Argentina, 3 Colombia, 2 Mexico, 1 Chile). Mostly (22/27, 81%) were published as abstracts; 5 were published as full text articles (19%). Dates for these publications ranged from 2002 to 2013, with an exponential increase over time. The number of MS patients is increasing rapidly (71% increase in Brazil between 2006 and 2009). However, hospitalization rates (overall and per patient) have been decreasing, as newer more effective drugs have been increasingly used. Disease modulating therapies are predominantly used. Costs of care are quite high and have risen dramatically, e. g. > 200% in Brazil between 2007-2012, with beta-interferons mostly used (78%). Some high cost drugs such as fingolimod and natalizumab have been found cost-effective over older drugs such as beta-interferons or glatiramer acetate in Mexico, Brazil and Colombia, with modest impact on budgets. ConClusions: Very little evidence related to cost of MS has been produced in Latin America. More research is needed to better support decisions regarding care of MS patients.

Background: In elderly patients (≥65 years of age) with epilepsy who take medications for comorbid conditions, some antiepileptic drugs (AEDs) may alter the metabolism of other treatments and increase the risk of adverse consequences and healthcare utilisation. This analysis compares healthcare costs associated with enzyme-inducing AEDs (EIAEDs) and non-enzyme active AEDs (nEAAEDs) use in elderly patients with epilepsy. Methods: This retrospective matched cohort study used the Clinical Practice Research Datalink (CPRD) of UK primary care medical records, linked to the Hospital Episode Statistics (HES) database. Selected patients with epilepsy were ≥ 65 years and prescribed an EIAED or nEAAED between 2001 and 2010 (index) after ≥1 year without AEDs (baseline) and followed until the first occurrence of the following: end of HES data coverage, end of GP registration, or death; practice's up-to-standard status or addition of an AED belonging to another cohort or discontinuation of the last AED of that cohort. Propensity score matching reduced confounding factor effects between cohorts. Key outcomes included time to cohort treatment failure, time to index AED treatment failure, and direct healthcare costs in 2014 Pound Sterling (£) values. Results: Overall, 1425 elderly patients were included: 964 with EIAEDs and 461 with nEAAEDs. At baseline, the EIAED cohort was older (mean age, 76.2 vs. 75.1 years) and a higher proportion were male. Baseline direct healthcare costs were similar. After matching (n = 210 each), and over the entire follow-up period, median monthly direct healthcare costs were higher for patients taking EIAEDs than nEAAEDs (£403 vs. £317; p = 0.0150, Mann-Whitney U). Costs were higher for patients remaining in the EIAED cohort after 3 follow-up years. The median time to cohort treatment failure for the EIAED cohort was 1110 days vs. 1175 days for the nEAAED cohort. Conclusion: Newly treated elderly patients with epilepsy were more likely to be prescribed EIAEDs than nEAAEDs. In matched cohorts, elderly patients with epilepsy treated with EIAEDs had higher average total direct and epilepsyrelated healthcare costs than nEAAED-treated patients; this difference was greater than previously reported in the overall adult population. Changing treatment practices could improve patient care and reduce costs.

A629ment was associated with 38% fewer unplanned admissions (981 vs. 604, X 1 2 = 89.2, p< 0.001) and 58% fewer unplanned bed nights (8,817 vs. 3,681, X 1 2 = 2109.8, p< 0.001) in the year following treatment initiation compared with the year before. A 14% reduction in all outpatient appointments was also observed, due principally to a 25% reduction in neurological outpatient appointments (from 7,826 to 5,901, X 1 2 = 269.7, p< 0.001). Evidence from this study indicates that duration of treatment is a significant factor in this response; patients receiving between 12 and 14 doses (n= 1,122) experienced 70% reduction in unplanned admissions and 90% reduction in unplanned bed nights. ConClusions: Our data support the notion that natalizumab treatment significantly reduces unplanned hospital treatment and outpatient attendance.