Cognitive outcomes of anti‐amyloid‐β monoclonal antibodies in patients with Alzheimer's disease: A systematic review and meta‐analysis of randomized controlled trials

Fernandez, Paulo Eduardo Lahoz; Silva, Guilherme Diogo

doi:10.1002/alz.057778

Cited by 6 publications

(7 citation statements)

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“…In (23). Other analyses did not estimate a cognitive benefit per amyloid change, but indicated either null effects or small benefits were plausible (6)(7)(8)(9)(10). None of these meta-analyses include the most recent data from CLARITY-AD (1) or GRADUATE I & II (unpublished).…”

Section: Discussionmentioning

confidence: 99%

“…The results of the CLARITY-AD trial rekindled discussion and debate on the value of reducing brain amyloid levels with amyloid-targeting drugs (1)(2)(3)(4). Previous meta-analyses of randomized trials of amyloid-targeting drugs suggested the effects of amyloid-removal on cognitive outcomes were close to null (5)(6)(7)(8)(9)(10), and these studies continue to be cited and referenced as evidence that an overall effect of this mechanism is likely to be negligible. Some have interpreted the small statistically significant effects reported in CLARITY-AD as unconvincing.…”

Section: Introductionmentioning

confidence: 99%

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Estimated Effects of Amyloid Reduction on Cognitive Change: A Bayesian Update across a Range of Priors

Ackley

Wang

Chen

et al. 2023

Preprint

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Introduction: Results of the CLARITY-AD and GRADUATE I and II trials rekindled discussion on the impact of amyloid-targeting drugs. We use a Bayesian approach to quantify how a rational observer might update their prior beliefs based on new trial results. Methods: We used publicly available data from the CLARITY-AD and GRADUATE I & II trials to estimate the effect of reducing amyloid on CDR-SB score. A range of prior positions were then updated according to Bayes Theorem using these estimates. Results: After updating with new trial data, a wide range of starting positions resulted in credible intervals that did not include no effect of amyloid reduction on CDR-SB. Discussion: For a range of starting beliefs and assuming veracity of underlying data, rational observers would conclude there is a small benefit of amyloid-reductions due to amyloid targeting drugs on cognition. This benefit must be weighed against opportunity cost and side effect risk.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Estimated Effects of Amyloid Reduction on Cognitive Change: A Bayesian Update across a Range of Priors

Ackley

Wang

Chen

et al. 2023

Preprint

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“…24 Other analyses did not estimate a cognitive benefit per amyloid change but indicated either null effects or small benefits were plausible. [7][8][9][10][11] None of these meta-analyses include the most recent data from CLARITY-AD, 1 GRADUATE I and II (unpublished), and TRAILBLAZER-ALZ 2. 5 Some researchers argue, based on qualitative assessment of the trials 40 and animal models, that amyloid removal has non-linear effects on cognition, with benefits only becoming apparent once a large fraction of amyloid has been removed.…”

Section: Discussionmentioning

confidence: 99%

“…included data from the phase II PRIME trial of aducanumab, one of the most optimistic trials of the benefits of amyloid removal to date (cognitive change per SUVR change), and obtained an estimate that indicated overall benefit 24 . Other analyses did not estimate a cognitive benefit per amyloid change but indicated either null effects or small benefits were plausible 7–11 . None of these meta‐analyses include the most recent data from CLARITY‐AD, 1 GRADUATE I and II (unpublished), and TRAILBLAZER‐ALZ 2 5…”

Section: Discussionmentioning

confidence: 99%

Estimated effects of amyloid reduction on cognitive change: A Bayesian update across a range of priors

Ackley,

Wang,

Chen

et al. 2023

Alzheimer's & Dementia

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INTRODUCTIONThe results of the CLARITY‐AD, GRADUATE I and II, and TRAILBLAZER‐ALZ 2 trials have rekindled discussion on the impact of amyloid‐targeting drugs. We use a Bayesian approach to quantify how rational observers would have updated their prior beliefs based on new trial results.METHODSWe used publicly available data from the CLARITY‐AD, GRADUATE I and II, and TRAILBLAZER‐ALZ 2 trials to estimate the effect of reducing amyloid on the clinical dementia rating scale, sum of boxes (CDR‐SB) score. A range of prior positions were then updated according to Bayes’ theorem using these estimates.RESULTSAfter updating with new trial data, a wide range of starting positions resulted in credible intervals that did not include no effect of amyloid reduction on CDR‐SB score.DISCUSSIONFor a range of starting beliefs and assuming the veracity of the underlying data, rational observers would conclude there is a small benefit of amyloid reductions on cognition. This benefit must be weighed against opportunity cost and side‐effect risk.Highlights The results of recent trials of amyloid‐targeting drugs have rekindled discussion on the impact of amyloid reductions achieved with amyloid‐targeting drugs on cognition. Prior to the announcement of trial results, beliefs about the effects of altering amyloid levels varied. For a range of starting beliefs, one would conclude there is a small benefit of amyloid reductions due to amyloid‐targeting drugs on cognition. The perceived value of individual drugs must balance the magnitude of this benefit against opportunity cost and risk of side effects.

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“…Alzheimer's disease (AD) has been historically known for its lack of effective treatments, despite decades of research. However, the FDA's approval of aducanumab as the first AD—modifying treatment in 2021, followed by approval of lecanemab in 2023, created significant hope among patients and speculation among providers (Abbott, 2022; Budd Haeberlein et al, 2022; Fernandez & Silva, 2021; Mahase, 2023). While most disease‐modifying treatments are perceived positively by the public and highly sought after, which individuals would seek a preventative treatment prior to a diagnosis is less widely understood.…”

Section: Introductionmentioning

confidence: 99%

Public perspective on medications to delay Alzheimer's disease symptoms

Rich

Zawatsky

Botta³

et al. 2023

Journal of Genetic Counseling

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Disease‐modifying treatments for Alzheimer's disease are emerging. Our research examined how personal risk for AD may influence intentions to ask for medications to delay symptoms of AD, and how the availability of such medications impacts interest in AD‐related genetic testing. Invitations to a web‐based survey were posted on social media sites. Respondents were sequentially assigned to imagine that they had a 5%, 15%, or 35% chance of developing AD. They were then provided a hypothetical scenario describing a medication that delayed AD symptoms. After reporting intentions to ask for the medication, respondents were asked about their interest in genetic testing to predict AD risk. Data from 310 individuals were analyzed. Intentions to ask for a preventative medication were greater for respondents presented AD risks of 35% compared to risks of 15% and 5% (86% vs. 66% vs. 62%, respectively, p < 0.001). The proportion who would ask for genetic susceptibility testing increased from 58% to 79% when respondents were told to imagine that a medication that delayed AD symptoms existed (p < 0.001). Findings suggest that individuals who know they have an increased risk for AD are more likely pursue medications to delay onset of disease symptoms, and the availability of AD‐delaying treatments will increase interest in associated genetic testing. Findings provide insight about who will pursue emerging preventative medications, including individuals for whom the medications may be inappropriate, and the impact on genetic test utilization.

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Cognitive outcomes of anti‐amyloid‐β monoclonal antibodies in patients with Alzheimer's disease: A systematic review and meta‐analysis of randomized controlled trials

Cited by 6 publications

References 0 publications

Estimated Effects of Amyloid Reduction on Cognitive Change: A Bayesian Update across a Range of Priors

Estimated Effects of Amyloid Reduction on Cognitive Change: A Bayesian Update across a Range of Priors

Estimated effects of amyloid reduction on cognitive change: A Bayesian update across a range of priors

Public perspective on medications to delay Alzheimer's disease symptoms

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