Advances in amyloid-targeting monoclonal antibodies for Alzheimer’s disease: clinical and public health issues

ABSTRACT

Introduction

Alzheimer’s disease (AD) is a major global public health challenge. To date, no treatments have been shown to stop the underlying pathological processes. The cerebral accumulation of amyloid-beta (Ab) is still considered as the primum movens of AD and disease-modifying treatments targeting Ab are reaching – or have already reached – clinical practice.

Areas covered

The authors explore the main advancements from Aβ-targeting monoclonal antibodies (mAbs) for the treatment of AD. From a public health perspective, they address ethically relevant issues such as the benevolence and non-maleficence principles. They report on the potential biological and clinical benefits of these drugs, discussing minimal clinically important differences (MCID) and other relevant outcomes. They examine the short- and long-term effects of amyloid-related imaging abnormalities (ARIA), and explore the differences between eligibility criteria in clinical trials, appropriate use recommendations, and prescribing information content. In doing so, they contextualize the discussion on the disagreements among different regulatory authorities.

Expert opinion

Although anti-β-amyloid monoclonal antibodies may be effective in selected scenarios, non-negligible knowledge gaps and implementation limits persist. Overcoming these gaps can no longer be postponed if we are to ensure the principles of Quality of Care for patients with cognitive impairment who would be eligible for this class of drugs.

KEYWORDS:

• Alzheimer’s disease
• amyloid, monoclonal antibodies
• public health
• efficacy
• safety

Article highlights

• Responder analysis should be included in the statistical plans of clinical trials to quantify and standardize what is perceived as a clinically relevant change at the intra-individual level (MCID).

• Outcomes representative of the long-term benefits of Ab-targeting mAbs are needed to appropriately establish the clinical, social, and economic value of DMTs for Alzheimer’s disease.

• Validation of amyloid plaque removal as a surrogate endpoint for AD is a cross-cutting process, whose results may have a major impact on Ab-targeting mAbs as a whole.

• Extensive and detailed longitudinal data on ARIA are needed to accurately estimate the risk/benefit balance of anti–β-amyloid mAbs.

• Poor reporting of comorbidities and non-neurological concomitant therapies of participants clinical trials strongly limits the possibility of taking evidence-based clinical decisions.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.