Donanemab in Early Symptomatic Alzheimer’s Disease: Efficacy and Safety in TRAILBLAZER‐ALZ 2, a Phase 3 Randomized Clinical Trial
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Le résumé fourni par la source
Abstract Background In TRAILBLAZER‐ALZ, donanemab cleared brain amyloid plaques and significantly slowed disease progression in early symptomatic Alzheimer’s disease (AD). Methods TRAILBLAZER‐ALZ 2 (NCT04437511), a multicenter, randomized, double‐blind, placebo‐controlled trial, enrolled participants with early symptomatic AD and amyloid and tau pathology by positron‐emission tomography. The study randomized participants with low/medium‐tau (n = 1182) and high‐tau (n = 552) pathology (missing tau category, n = 2). Participants (randomized 1:1) received donanemab (n = 860) or placebo (n = 876) intravenously every 4 weeks (w) for 72w. Donanemab participants meeting amyloid clearance treatment completion criteria at 24w or 52w were switched to placebo in a blinded procedure. The primary outcomes were change in Integrated AD Rating Scale (iADRS) score from baseline at 76w in either the low/medium‐tau or combined (low/medium‐tau and high‐tau) populations. Statistical testing allocated most power (80% alpha spend) to low/medium‐tau population outcomes, with the remainder for combined population outcomes, which included clinical and biomarker assessments. Results In the low/medium‐tau population, change in iADRS score at 76w was ‐6.02 with donanemab and ‐9.27 with placebo (difference, 3.25; 95% CI, 1.88 to 4.62; P <0.001), representing a 35.1% slowing of disease progression. Change in Clinical Dementia Rating Scale (CDR) – Sum of Boxes, the key secondary outcome, was 1.20 with donanemab and 1.88 with placebo (difference, ‐0.67; 95% CI ‐0.95 to ‐0.40; P <0.001), representing a 36.0% slowing. Participants receiving donanemab experienced a 38.6% lower risk of progressing to the next disease stage versus placebo over 76w (CDR‐Global score, Hazard Ratio = 0.61; P <0.001). Amyloid clearance at 24w, 52w and 76w was achieved in 34.2%, 71.3% and 80.1% of donanemab‐treated participants, respectively. Plasma P‐tau217 was significantly reduced by 39.3% from baseline with donanemab and increased by 8.4% with placebo at 76w ( P <0.001). Significant, positive results across all clinical endpoints were also observed in the combined population. The incidence of serious adverse events was 17.4% (donanemab) and 15.8% (placebo), with three deaths among patients treated with donanemab who experienced serious ARIA. Adverse events with donanemab included amyloid‐related imaging abnormalities (ARIA)‐E (24.0%, 6.1% symptomatic); ARIA‐H (31.4%); and infusion‐related reactions (8.7%). Conclusion Donanemab treatment significantly slowed clinical progression at 76w and had a safety profile consistent with earlier studies.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Donanemab in Early Symptomatic Alzheimer’s Disease: Efficacy and Safety in TRAILBLAZER‐ALZ 2, a Phase 3 Randomized Clinical Trial
- Date Crossref
- 01/12/2023
- Éditeur
- Wiley
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Eli Lilly (United States) pays non établi dans la noticeEntreprise
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Boston University pays non établi dans la noticeUniversité ou école supérieure
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Boston Center for Memory pays non établi dans la noticeÉtablissement de santé
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Lund University Clinical Memory Research Unit pays non établi dans la noticeUniversité ou école supérieure
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Skåne University Hospital Memory Clinic pays non établi dans la noticeÉtablissement de santé
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Indiana University School of Medicine Department of Neurology pays non établi dans la noticeUniversité ou école supérieure
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Eli Lilly (United States), Boston University et Boston Center for Memory, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.