PMID- 38253509
OWN - NLM
STAT- MEDLINE
DCOM- 20240124
LR  - 20240417
IS  - 1544-1717 (Electronic)
IS  - 1544-1709 (Linking)
VI  - 22
IP  - 1
DP  - 2024 Jan-Feb
TI  - Clinically Important Benefits and Harms of Monoclonal Antibodies Targeting 
      Amyloid for the Treatment of Alzheimer Disease: A Systematic Review and 
      Meta-Analysis.
PG  - 50-62
LID - 10.1370/afm.3050 [doi]
AB  - PURPOSE: We conducted a meta-analysis to evaluate clinically meaningful benefits 
      and harms of monoclonal antibodies targeting amyloid in patients with Alzheimer 
      dementia. METHODS: We searched PubMed, Cochrane CENTRAL, and 5 trial registries, 
      as well as the reference lists of identified studies. We included randomized 
      controlled trials comparing a monoclonal antibody with placebo at a dose 
      consistent with that used in phase 3 trials or for Food and Drug Administration 
      approval. Studies had to report at least 1 clinically relevant benefit or harm. 
      Data were extracted independently by at least 2 researchers for random effects 
      meta-analysis. Changes in cognitive and functional scales were compared between 
      groups, and each difference was assessed to determine if it met the minimal 
      clinically important difference (MCID). RESULTS: We identified 19 publications 
      with 23,202 total participants that evaluated 8 anti-amyloid antibodies. There 
      were small improvements over placebo in the Alzheimer's Disease Assessment Scale 
      (ADAS)-Cog-11 to -14 score (standardized mean difference = -0.07; 95% CI, -0.10 
      to -0.04), Mini Mental State Examination score (0.32 points; 95% CI, 0.13 to 
      0.50), and Clinical Dementia Rating-Sum of Boxes scale score (mean difference 
      =-0.18 points; 95% CI, -0.34 to -0.03), and the combined functional scores 
      (standardized mean difference = 0.09; 95% CI, 0.05 to 0.13). None of the changes, 
      including those for lecanemab, aducanumab, and donanemab, exceeded the MCID. 
      Harms included significantly increased risks of amyloid-related imaging 
      abnormalities (ARIA)-edema (relative risk [RR] = 10.29; number needed to harm 
      [NNH] = 9), ARIA-hemorrhage (RR = 1.74; NNH = 13), and symptomatic ARIA-edema (RR 
      = 24.3; NNH = 86). CONCLUSIONS: Although monoclonal antibodies targeting amyloid 
      provide small benefits on cognitive and functional scales in patients with 
      Alzheimer dementia, these improvements are far below the MCID for each outcome 
      and are accompanied by clinically meaningful harms.
CI  - (c) 2024 Annals of Family Medicine, Inc.
FAU - Ebell, Mark H
AU  - Ebell MH
AD  - Department of Epidemiology and Biostatistics, College of Public Health, the 
      University of Georgia, Athens, Georgia ebell@uga.edu.
FAU - Barry, Henry C
AU  - Barry HC
AD  - Department of Family Medicine, College of Human Medicine, Michigan State 
      University, East Lansing, Michigan.
FAU - Baduni, Kanishka
AU  - Baduni K
AD  - Department of Kinesiology, College of Education, the University of Georgia, 
      Athens, Georgia.
FAU - Grasso, Gabrielle
AU  - Grasso G
AD  - Department of Epidemiology and Biostatistics, College of Public Health, the 
      University of Georgia, Athens, Georgia.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Review
PT  - Systematic Review
PL  - United States
TA  - Ann Fam Med
JT  - Annals of family medicine
JID - 101167762
RN  - 0 (donanemab)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
SB  - IM
MH  - United States
MH  - Humans
MH  - *Alzheimer Disease/drug therapy
MH  - Antibodies, Monoclonal/therapeutic use
MH  - Mental Status and Dementia Tests
MH  - Edema
MH  - *Antibodies, Monoclonal, Humanized
OTO - NOTNLM
OT  - ARIA
OT  - Alzheimer dementia
OT  - Alzheimer disease
OT  - aducanumab
OT  - aged
OT  - amyloid
OT  - antibodies, monoclonal
OT  - biological therapy
OT  - cerebral edema
OT  - cerebral hemorrhage
OT  - chronic disease
OT  - dementia
OT  - donanemab
OT  - drug approval
OT  - lecanemab
OT  - meta-analysis
OT  - risks and benefits
OT  - systematic review
EDAT- 2024/01/23 00:42
MHDA- 2024/01/24 06:44
CRDT- 2024/01/22 23:31
PHST- 2023/05/04 00:00 [received]
PHST- 2023/09/20 00:00 [revised]
PHST- 2023/09/21 00:00 [accepted]
PHST- 2024/01/24 06:44 [medline]
PHST- 2024/01/23 00:42 [pubmed]
PHST- 2024/01/22 23:31 [entrez]
AID - 22/1/50 [pii]
AID - 10.1370/afm.3050 [doi]
PST - ppublish
SO  - Ann Fam Med. 2024 Jan-Feb;22(1):50-62. doi: 10.1370/afm.3050.