RESUMO
OBJECTIVE: To review current pharmacology, pharmacokinetics/pharmacodynamics, safety, and efficacy of lecanemab in patients with Alzheimer disease. DATA SOURCES: A literature search of PubMed (April 1, 2016-November 15, 2023) and ClinicalTrials.gov search were conducted using the following search terms: lecanemab and BAN2401. Additional articles were identified by hand from references. STUDY SELECTION AND DATA EXTRACTION: We included English-language clinical trials, randomized controlled trials, reviews, and systematic reviews evaluating lecanemab pharmacology, efficacy, or safety in humans for the management of Alzheimer disease. DATA SYNTHESIS: In the Clarity AD phase III trial, lecanemab led to a decrease in brain amyloid levels and showed moderate improvement in clinical measures of cognition and function. At 18 months, lecanemab 10 mg/kg biweekly exhibited a lower least squares mean change from baseline (1.21) compared to placebo (1.66) of Clinical Dementia Rating-Sum of Boxes score, signifying a significant difference of -0.45 (95% CI, -0.67 to -0.23; P < 0.001). In a subset of 698 participants, lecanemab reduced brain amyloid burden by -59.1 Centiloids (95% CI, -62.6 to -55.6). Lecanemab demonstrated favorable differences in Alzheimer Disease Assessment Scale-cognitive subscale 14, Alzheimer Disease Composite Score, and Alzheimer Disease Cooperative Study-Mild Cognitive Impairment-Activities of Daily Living scores. Adverse events included infusion-related reactions (26.4%) and amyloid-related imaging abnormalities (12.6%). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Lecanemab reduces cognitive decline but raises concerns about intravenous administration, cost, and magnetic resonance imaging needs. Ongoing trials exploring subcutaneous dosing and positron emission tomography scans may offer solutions. CONCLUSION: Lecanemab is a humanized monoclonal antibody that is selective for soluble amyloid-beta (Aß) aggregates. Lecanemab has exhibited a decrease in brain Aß plaques and moderately less decline on clinical measures of cognitive function.
RESUMO
OBJECTIVE: To review the current pharmacology, pharmacokinetics/pharmacodynamics, safety, and efficacy of daridorexant in patients with insomnia. DATA SOURCES: A literature search of PubMed (March 1, 2018, to October 19, 2022) and ClinicalTrials.gov search was conducted using the following terms: daridorexant and ACT-541468. Additional articles were identified by hand from references. STUDY SELECTION AND DATA EXTRACTION: We included English-language articles evaluating daridorexant pharmacology, efficacy, or safety in humans for the management of insomnia. DATA SYNTHESIS: Daridorexant has a peak plasma concentration of 1-2 hours, terminal half-life of 8 hours, and absolute bioavailability of 61%. Wake after sleep onset (WASO) significantly decreased from baseline to months 1 and 3 in daridorexant 25 (-18.40 and -22.97 min, P < 0.0001) and 50 mg (-28.98 and -29.41 min, P < 0.0001) groups compared with placebo. Latency to persistent sleep (LPS) significantly decreased from baseline to months 1 and 3 for daridorexant 25 mg (-28.17 and -30.73 min, P = 0.0005 and P = 0.0015) and 50 mg (-31.20 and -34.80 min, P < 0.0001). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON TO EXISTING AGENTS: Daridorexant can be administered in diverse patient populations because of its tolerability and favorable safety profile. However, due to the lack of large scale studies that directly compare dual orexin receptor antagonists (DORAs), there is not enough data to recommend 1 DORA over another. CONCLUSIONS: Daridorexant is well tolerated and has demonstrated significant reductions in LPS and WASO in the treatment of insomnia in adult patients.
