Anti-Aβ agents for mild to moderate Alzheimer's disease: systematic review and meta-analysis

• Published in: Journal of neurology, neurosurgery and psychiatry Vol. 91; no. 12; pp. 1316 - 1324
• Main Authors: Lu, Liming, Zheng, Xiaoyan, Wang, Shengwen, Tang, Chunzhi, Zhang, Yuqing, Yao, Gaolei, Zeng, Jingchun, Ge, Shuqi, Wen, Hao, Xu, Mingzhu, Guyatt, Gordon, Xu, Nenggui
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 01.12.2020; BMJ Publishing Group LTD
• Subjects: Acitretin - therapeutic use; Activities of daily living; Alanine - analogs & derivatives; Alanine - therapeutic use; Alzheimer Disease - drug therapy; Alzheimer Disease - metabolism; Alzheimer Disease - physiopathology; Alzheimer Disease - psychology; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Amyloid beta-Peptides - therapeutic use; Antibodies, Monoclonal, Humanized - therapeutic use; Anxiety - chemically induced; Azepines - therapeutic use; Bias; Clinical trials; Clioquinol - analogs & derivatives; Clioquinol - therapeutic use; Cognitive ability; Copper - therapeutic use; Cyclic S-Oxides - therapeutic use; Dementia; Depression - chemically induced; Diarrhea - chemically induced; Drug dosages; Exanthema - chemically induced; Fatigue - chemically induced; Flurbiprofen - therapeutic use; Humans; Hypotheses; Immunoglobulins, Intravenous - therapeutic use; Inositol - therapeutic use; Mental Status and Dementia Tests; Meta-analysis; Minimal Clinically Important Difference; Neurodegeneration; Orotic Acid - therapeutic use; Oxadiazoles - therapeutic use; Severity of Illness Index; Software; Subject heading schemes; Sulfonamides - therapeutic use; Syncope - chemically induced; Systematic review; Thiadiazines - therapeutic use; Treatment Outcome; Vomiting - chemically induced; Web portals
• ISSN: 0022-3050; 1468-330X; 1468-330X
• DOI: 10.1136/jnnp-2020-323497

ObjectiveTo assess the efficacy and safety of Aβ-targeting agents for mild to moderate Alzheimer’s disease.MethodsThe MEDLINE, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, ClinicalTrials.gov and the WHO’s International Clinical Trials Registry Platform search portal were searched from their inception to April 2020. We generated pooled estimates using random effects meta-analyses.ResultsNineteen randomised controlled trials, of which 17 had a low risk of bias, included 12 903 participants. The meta-analysis showed no difference in the cognitive subscale of Alzheimer’s Disease Assessment Scale (ADAS-Cog) between anti-Aβ drugs and placebo (mean difference (MD): 0.20, 95% CI −0.40 to 0.81; I 2=99.8%; minimal important difference 3.1–3.8 points, moderate-certainty evidence). For ADAS-Cog, results suggested that one drug that increases Aβ clearance may differ in effect (MD: −0.96, 95% CI −0.99 to −0.92) from drugs that reduce Aβ production (MD: 0.78, 95% CI 0.25 to 1.32) (interaction p<0.000001); this difference also existed in the outcome of MMSE and CDR-SOB. Compared with placebo, anti-Aβ drug-related adverse events were as follows: anxiety, depression, diarrhoea, fatigue, rash, syncope and vomit.DiscussionFrom current evidence, anti-Aβ interventions are unlikely to have an important impact on slowing cognitive or functional decline. Although the subgroup analysis suggested possible benefits from Aβ clearance drugs, the analysis has limited credibility, and a benefit from drugs that increase clearance, if real, is very small.Trial registration numberPROSPERO registration number CRD42019126272.