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P1‐043: Immunotherapy Targeting Amyloid‐Beta in Alzheimer's Disease: A Meta‐Analysis
Author(s) -
Penninkilampi Ross,
Brothers Holly M.,
Eslick Guy D.
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.06.790
Subject(s) - medicine , incidence (geometry) , adverse effect , meta analysis , oncology , clinical trial , subgroup analysis , disease , immunotherapy , cancer , physics , optics
Background:b-amyloid has been posited to be central to the pathogenesis of Alzheimer’s disease (AD), in what has been called the ‘amyloid cascade hypothesis’. In recent years, there has been extensive testing of novel immunotherapeutics targeting b-amyloid in AD, with mixed results. Methods: Thirteen trials were identified involving 5554 patients were identified in a systemic search of electronic databases and manual examination of references. Randomised controlled trials involving immunotherapeutic agents targetingb-amyloid and involving the infusion of more than a single dose were eligible for inclusion. Overall, there were 4 trials for bapineuzumab, 4 trials for solanezumab, 2 trials each for CAD106 and AN1792, and 1 trial each for aducanumab, gantenerumab, and ponezumab. The main outcome to be assessed was the incidence of adverse effects, with separate analyses for the incidence of amyloid-related imaging abnormalities (ARIA), deaths, and all cancers. Results: There was no statistically significant increase in adverse effects (OR 1.04, 95%CI 0.97-1.12; p1⁄40.26), serious adverse events (OR 1.09, 95%CI 0.97-1.23; p1⁄40.16), cancer (OR 0.86, 95%CI 0.52-1.42; p1⁄40.56) or mortality (OR 1.31, 95%CI 0.87-1.98; p1⁄40.19). There was a trend towards increased mortality in the subgroup analysis of bapineuzumab only, but this was not statistically significant (OR 1.83, 95%CI 0.95-3.52; p1⁄40.07). There was a significant increased risk of developing ARIA (OR 4.81, 95%CI 1.2418.66; p1⁄40.02), which was mainly due to the high incidence of vasogenic edema in studies of bapineuzumab. Subgroup analysis found bapineuzumab had a very large increase in risk of ARIA (OR 27.83, 95%CI 7.61-101.93; p<0.001), while none of the other drug subgroups had a statistically significant change. Conclusions: The pooled results indicate that ARIA is a significant concern in the development of immunotherapeutics targeting b-amyloid, however subgroup analysis revealed that this was mainly due to the impact of bapineuzumab trials. The lack of increased risk of adverse effects, serious adverse effects and death indicate that most immunotherapeutic agents have an acceptable safety profile. Promisingly, solanezumab has not shown an increased risk of ARIA and has a favourable safety profile.