Value contribution of cenobamate for the treatment of Focal-Onset Seizures (FOS) in patients with drug-resistant epilepsy (DRE) in Spain through reflective Multi-Criteria Decision Analysis (MCDA).

INTRODUCTION: Epilepsy is one of the most common neurological conditions worldwide. The main goal of its treatment is to achieve seizure freedom without intolerable adverse effects. However, despite the availability of many anti-seizure medications, including the latest options, called third-generation anti-seizure medications (ASMs), approximately 40% of people with epilepsy present drug-resistant epilepsy (DRE). Cenobamate is the first ASM approved in Spain for the adjunctive treatment of Focal-Onset Seizures (FOS) in adult patients with DRE. In a chronic disease with a portfolio of available ASMs, the decision to introduce a new therapeutic alternative must follow a holistic evaluation of value provided. Reflective Multi-Criteria Decision Analysis (MCDA) methodology allows to determine the value contribution of a treatment in a given indication considering all relevant criteria for healthcare decision-making in a transparent and systematic manner from the perspective of relevant stakeholders. PURPOSE: The aim of this study was to determine the relative value contribution of cenobamate in the treatment of FOS in patients with DRE compared with third-generation ASMs using reflective MCDA-based methodology. METHODS: A systematic literature review (combining biomedical databases and grey literature sources) was performed to populate the Evidence and Value: Impact on DEcisionMaking (EVIDEM) MCDA framework adapted to determine what represents value in the management of FOS in patients with DRE in Spain. The study was conducted in two phases. The first took place in 2021 with a multi-stakeholder group of eight participants. The second phase was conducted in 2022 with a multi-stakeholder group of 32 participants. Participants were trained in MCDA methodology and scored four evidence matrices (cenobamate vs. brivaracetam, vs. perampanel, vs. lacosamide and vs. eslicarbazepine acetate). Results were analyzed and discussed in a group meeting through reflective MCDA discussion methodology. RESULTS: DRE is considered a very severe condition associated with many important unmet needs, mainly with regard to the lack of more effective treatments to achieve the ultimate goal of treatment. Compared to third-generation ASMs, cenobamate is perceived to have a better efficacy profile based on improvements in responder rate and seizure freedom. Regarding safety, it is considered to have a similar profile to alternatives and a positive quality-of-life profile. Cenobamate results in lower direct medical costs (excluding pharmacological) and indirect costs. Overall, cenobamate is regarded as providing a high therapeutic impact and supported by high-quality evidence. CONCLUSIONS: Based on reflective MCDA methodology and stakeholders' experience in clinical management of epilepsy in Spain, cenobamate is perceived as a value-added option for the treatment of patients with DRE when compared with third-generation ASMs.

Compliance with the DPP-4 inhibitors dose adjustment recommendations based on renal function in a population database. / Cumplimiento de las recomendaciones de ajuste de la dosis de inhibidores DPP4 según la función renal en una base de datos poblacional.

OBJECTIVE: To examine the prescription pattern of the different dipeptidyl peptidase-4 inhibitors (DPP4is), depending on the estimated glomerular filtration rate (eGFR) under real-world clinical practice conditions. METHOD: This was a descriptive, observational study using a population database (SIDIAP Catalonia). Subjects diagnosed with T2DM with kidney function assessed and on active treatment with DPP4is were enrolled. Patients were included at the time of the measurement of eGFR (CKD-EPI) and were monitored for 6 months after enrolment. For each subject, the prescribed daily dose (PDD) of DPP4i, the theoretical dose according to the degree of renal failure established by the recommendations in the summary of product characteristics (DDD-adj), and the PDR ratio (PDD/DDD-adj) were estimated. A subject was considered overtreated if his/her RDR was greater than 1.2 (>20%). RESULTS: The study sample consisted of 72,135 subjects with a mean age of 69.7 (±11.6) years and 55.9% males. The proportion of patients overtreated varied depending on the type of DPP4i and the renal function stage. Overall, overdosage was recorded in 7.15% of all DPP4i treatments. In advanced stages (IIIb, IV and V), overdosage was much higher (36.8% for all DPP4is, and 58.7% if linagliptin is excluded). DISCUSSION: Under real-world clinical practice conditions, more than one third of T2DM patients with advanced renal failure were overdosed with DPP4is because the doses were not adequately adjusted to the glomerular filtration rate of each patient.