Clinical Benefits and Risks of Anti-Amyloid Antibodies in Sporadic Alzheimer’s Disease: Systematic Review and Network Meta-Analysis with Web Application (Preprint) DOI Creative Commons
Danko Jeremic, Juan D. Navarro‐López, Lydia Jiménez‐Díaz

et al.

Journal of Medical Internet Research, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 6, 2024

Despite the increasing approval of antiamyloid antibodies for Alzheimer disease (AD), their clinical relevance and risk-benefit profile remain uncertain. The heterogeneity AD limited availability long-term data make it difficult to establish a clear rationale selecting one treatment over another. aim this work was assess compare efficacy safety through an interactive online meta-analytic approach by performing conventional pair-wise meta-analyses frequentist Bayesian network phase II III trial results. To achieve this, we developed AlzMeta.app 2.0, freely accessible web application that enables researchers clinicians evaluate relative absolute risks benefits these therapies in real time, incorporating different prior choices assumptions baseline progression adverse events. We adhered PRISMA-NMA (Preferred Reporting Items Systematic Reviews Meta-Analyses extension reporting systematic reviews with meta-analysis) GRADE (Grading Recommendations, Assessment, Development, Evaluation) guidelines rating certainty evidence. Clinical reports (until September 30, 2024) were retrieved from PubMed, Google Scholar, databases (including ClinicalTrials.gov). Studies <20 sporadic patients modified Jadad score <3 excluded. Risk bias assessed RoB-2 tool. Relative have been expressed as risk ratios standardized mean differences, confidence, credible, prediction intervals calculated all outcomes. For significant results, intervention effects ranked frameworks, determined per 1000 people number needed treat (NNT) wide range control responses. Among 7 treatments tested 21,236 (26 studies low or some concerns), donanemab best-ranked on cognitive functional measures, almost 2 times more effective than aducanumab lecanemab significantly beneficial other global (cognitive functional) Dementia Rating Scale-Sum Boxes (NNT=10, 95% CI 8-16). Special caution is required regarding cerebral edema microbleeding due clinically relevant (NNT=8, 5-16), 6-17), (NNT=14, 7-31), which may outweigh benefits. Our results showed has similar lecanemab, highlighting need options improved safety. Potential introduced included trials unblinding caused frequent microbleeds, well impact COVID-19 pandemic.

Language: Английский

Clinical Benefits and Risks of Anti-Amyloid Antibodies in Sporadic Alzheimer’s Disease: Systematic Review and Network Meta-Analysis with Web Application (Preprint) DOI Creative Commons
Danko Jeremic, Juan D. Navarro‐López, Lydia Jiménez‐Díaz

et al.

Journal of Medical Internet Research, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 6, 2024

Despite the increasing approval of antiamyloid antibodies for Alzheimer disease (AD), their clinical relevance and risk-benefit profile remain uncertain. The heterogeneity AD limited availability long-term data make it difficult to establish a clear rationale selecting one treatment over another. aim this work was assess compare efficacy safety through an interactive online meta-analytic approach by performing conventional pair-wise meta-analyses frequentist Bayesian network phase II III trial results. To achieve this, we developed AlzMeta.app 2.0, freely accessible web application that enables researchers clinicians evaluate relative absolute risks benefits these therapies in real time, incorporating different prior choices assumptions baseline progression adverse events. We adhered PRISMA-NMA (Preferred Reporting Items Systematic Reviews Meta-Analyses extension reporting systematic reviews with meta-analysis) GRADE (Grading Recommendations, Assessment, Development, Evaluation) guidelines rating certainty evidence. Clinical reports (until September 30, 2024) were retrieved from PubMed, Google Scholar, databases (including ClinicalTrials.gov). Studies <20 sporadic patients modified Jadad score <3 excluded. Risk bias assessed RoB-2 tool. Relative have been expressed as risk ratios standardized mean differences, confidence, credible, prediction intervals calculated all outcomes. For significant results, intervention effects ranked frameworks, determined per 1000 people number needed treat (NNT) wide range control responses. Among 7 treatments tested 21,236 (26 studies low or some concerns), donanemab best-ranked on cognitive functional measures, almost 2 times more effective than aducanumab lecanemab significantly beneficial other global (cognitive functional) Dementia Rating Scale-Sum Boxes (NNT=10, 95% CI 8-16). Special caution is required regarding cerebral edema microbleeding due clinically relevant (NNT=8, 5-16), 6-17), (NNT=14, 7-31), which may outweigh benefits. Our results showed has similar lecanemab, highlighting need options improved safety. Potential introduced included trials unblinding caused frequent microbleeds, well impact COVID-19 pandemic.

Language: Английский

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