Donanemab, another anti-Alzheimer ' s drug with risk and uncertain benefit

被引:4
|
作者
Hoilund-Carlsen, Poul F. [1 ,2 ]
Alavi, Abass [3 ]
Barrio, Jorge R. [4 ]
Castellani, Rudolph J. [5 ]
Costa, Tommaso [6 ,7 ,8 ]
Herrup, Karl [9 ]
Kepp, Kasper P. [10 ]
Neve, Rachael L. [11 ]
Perry, George [12 ]
Revheim, Mona-Elisabeth [13 ,14 ]
Robakis, Nikolaos K. [15 ]
Sensi, Stefano L. [16 ,17 ,18 ]
Vissel, Bryce [19 ,20 ]
机构
[1] Odense Univ Hosp, Dept Nucl Med, DK-5000 Odense C, Denmark
[2] Univ Southern Denmark, Dept Clin Res, Odense, Denmark
[3] Hosp Univ Penn, Dept Radiol, Philadelphia, PA USA
[4] David Geffen UCLA, Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA USA
[5] Northwestern Univ, Feinberg Sch Med, Dept Pathol, Chicago, IL USA
[6] Univ Turin, Koelliker Hosp, GCS fMRI, Turin, Italy
[7] Univ Turin, Dept Psychol, Turin, Italy
[8] Univ Turin, Dept Psychol, FOCUS Lab, Turin, Italy
[9] Univ Pittsburgh, Dept Neurobiol, Pittsburgh, PA USA
[10] Tech Univ Denmark, Sect Biophys & Biomed Chem, DTU Chem, Kongens Lyngby, Denmark
[11] Massachusetts Gen Hosp, Gene Delivery Technol Core, Boston, MA USA
[12] Univ Texas San Antonio, Dept Neurosci Dev & Regenerat Biol, San Antonio, TX USA
[13] Oslo Univ Hosp, Intervent Ctr, Div Technol & Innovat, Oslo, Norway
[14] Univ Oslo, Inst Clin Med, Oslo, Norway
[15] Ctr Mol Biol & Genet Neurodegenerat, Icahn Sch Med Mt Sinai Med Ctr, Dept Psychiat & Neurosci, New York, NY USA
[16] G Annunzio Univ Chieti Pescara, Dept Neurosci Imaging & Clin Sci, Chieti, Pescara, Italy
[17] G Annunzio Univ Chieti Pescara, CAST Ctr Adv Studies & Technol, Chieti, Pescara, Italy
[18] G Annunzio Univ Chieti Pescara, ITAB Inst Adv Biomed Technol, Chieti, Pescara, Italy
[19] UNSW, St Vincents Healthcare Clin Campus Fac Med & Hlth, Sch Clin Med, UNSW Med & Hlth, Sydney, NSW, Australia
[20] St Vincents Hosp Sydney, St Vincents Hosp Ctr Appl Med Res, Darlinghurst, NSW, Australia
关键词
Donanemab; Aducanumab; Lecanemab; Alzheimer's disease; Amyloid-PET; ARIA; Brain volume; FDG-PET; AMYLOID-BETA; DISEASE; VOLUME;
D O I
10.1016/j.arr.2024.102348
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Based on "reducing amyloid plaques in the brain", the U.S. Food and Drug Administration has granted accelerated and full approval for two monoclonal anti-Alzheimer's antibodies, aducanumab and lecanemab, respectively. Approval of a third antibody, donanemab, is pending. Moreover, lecanemab and donanemab are claimed to cause delay in the cognitive decline that characterizes the disease. We believe that these findings are subject to misinterpretation and statistical bias. Donanemab is claimed to cause removal of up to 86 % of cerebral amyloid and 36 % delay in cognitive decline compared to placebo. In reality, these are very small changes on an absolute scale and arguably less than what can be achieved with cholinesterase inhibitor/memantine therapy. Moreover, the "removal" of amyloid, based on the reduced accumulation of amyloid-PET tracer, most likely also reflects therapy-related tissue damage. This would also correlate with the minimal clinical effect, the increased frequency of amyloid-related imaging abnormalities, and the accelerated loss of brain volume in treated compared to placebo patients observed with these antibodies. We recommend halting approvals of anti -AD antibodies until these issues are fully understood to ensure that antibody treatment does not cause more harm than benefit to patients.
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页数:5
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