Objectives: Combination regimens of antiepileptic drugs (AEDs) with various mechanisms of action (MOA) are commonly used in patients with refractory epilepsy. However, outcomes related to combination AEDs with novel MOA, such as perampanel (PER), are not well described. This study compared healthcare resource utilization (HRU) among recipients of PER-based combinations versus recipients of other non-PER-based combinations.
Methods: This retrospective study used claims data from the Symphony Health's IDV® (Integrated Dataverse) database (August 2012 to July 2018). Patients were aged ≥12 years with epilepsy or non-febrile convulsions, were treated with AED combinations, and had ≥12 and ≥6 months pre- and post-index date, respectively (date of initiation of the second AED in the combination). AEDs were categorized based on MOA: selective non-competitive antagonist of AMPA receptors (i.e., PER), sodium channel blocker (SC), synaptic vesicle protein 2A binding (SV2), and gamma-aminobutyric acid analog (G). Patients were then classified into MOA-based cohorts: PER + SC, PER + SV2, PER + G, SC + SC, SC + SV2, SC + G, SV2 + G, and G + G. HRU outcomes were evaluated during follow-up and compared between PER-based cohorts and non-PER-based cohorts.
Results: On average, patients in the PER + SC (N = 3,592), PER + SV2 (N = 2,200), and PER + G (N = 1,313) cohorts were younger and had a lower Quan-Charlson comorbidity index than those in non-PER-based cohorts. PER + SC and PER + SV2 users had significantly fewer all-cause hospitalizations than non-PER-based users (adjusted RR range: 0.66-0.89, all P < 0.05), while PER + G recipients had fewer all-cause hospitalizations than recipients of SV2 + G and G + G (adjusted RR range: 0.92-0.94). Similar trends were observed for epilepsy-related hospitalizations. Across all comparisons, PER-based combinations were associated with significantly lower rates of all-cause clinic/office/outpatient visits relative to non-PER-based combinations (adjusted RR range: 0.69-0.86, all P < 0.05).
Significance: Results showed that patients treated with PER-based combinations had fewer all-cause and epilepsy-related hospitalizations, and fewer all-cause clinic/office/outpatient visits compared with patients treated with most other non-PER-based combinations.
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http://dx.doi.org/10.1016/j.yebeh.2021.107927 | DOI Listing |
Background: CT1812 is an experimental therapeutic sigma-2 receptor modulator in development for Alzheimer's disease (AD) and dementia with Lewy bodies. CT1812 reduces the affinity of Aβ oligomers to bind to neurons and exert synaptotoxic effects. This phase 2, multi-center, international, randomized, double-blind, placebo-controlled trial assessed safety, tolerability and effects of CT1812 on cognitive function in individuals with AD.
View Article and Find Full Text PDFBackground: Differences in patient characteristics across geographical regions may result in heterogeneity in clinical trial populations. evoke (NCT04777396) and evoke+ (NCT04777409) are two phase 3, multinational, randomised trials investigating semaglutide versus placebo in individuals with mild cognitive impairment or mild dementia due to Alzheimer's disease (AD) (early AD). We present baseline characteristics across the geographical regions in evoke/evoke+.
View Article and Find Full Text PDFBackground: A large body of evidence now indicates that the most pathogenic species of Aß in Alzheimer's disease (AD) consist of soluble toxic oligomers (AßO) as opposed to insoluble fibrils and monomers. Using our computational platform, we identified 4 different AßO-restricted conformational B cell epitopes (300, 301, 303, 305) that were tested as vaccines for their ability to induce an antibody response that selectively targets toxic AßO, without inducing potentially detrimental B or T cell responses against plaque or normal Aß. A novel ex vivo approach was then used to select an optimal vaccine configuration amongst the 15 possible combinations of the 4 epitopes to provide maximal binding to a toxic oligomer-enriched low molecular weight (LMW) fraction of soluble AD brain extracts.
View Article and Find Full Text PDFBackground: Evidence suggests glucagon-like peptide 1 receptor agonists (GLP-1RAs) may have therapeutic potential in Alzheimer's disease (AD). Cumulative evidence has indicated a potential reduction in cognitive decline in people with AD, while real-world evidence has shown decreased dementia risk in patients with type 2 diabetes. Non-clinical data reveal that GLP-1RAs impact neuroinflammation and other biological processes believed to be involved in AD pathophysiology, including effects on central and peripheral immune cells.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Oxford, Oxford, Oxon, United Kingdom.
Background: An estimated ∼40% of dementia cases are due to modifiable risk factors which can be targeted in lifestyle interventions. Effective interventions employ face-to-face delivery, making them resource-intensive and burdensome. Digital interventions offer scalability, accessibility and cost-effectiveness.
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