System readiness for DMTs in Alzheimer's disease

Webinar outline

New drug treatments with the potential to modify Alzheimer disease (AD) are now becoming available, posing a challenge for integration into existing healthcare systems. Understanding public attitudes toward these treatments is essential. This study investigates public perspectives on the acceptability of disease-modifying therapies (DMTs) for AD, awareness of prevention/treatment, perceived benefits or risks, and willingness to pay (WTP) for DMTs. Here, we present an outline of how to ascertain numbers of potential eligible patients for DMTs, the components required to ensure a health system is 'ready' to deliver the treatments, and insights into public and patient acceptability of the treatments.

Objectives

• To appreciate an approach to ascertaining the number of potentially eligible patients for DMTs within a region
  
• To see the application of a framework to address system readiness to deliver DMTs for Alzheimer disease
• To understand motivations to accept DMTs in the general public, including 'willingness to pay'

Summary

After more than two decades of little progress in dementia treatment, a new wave of disease modifying therapies (DMTs) look set to transform the care landscape. But is the health system ready to adapt to this new frontier?

In this Dementia Academy webinar, Dr George Crowther, consultant in old age liaison psychiatry, Leeds and York Partnership Foundation Trust, and professor in geriatric psychiatry at Dublin’s Trinity College, Iracema Lerio, spoke about how we got here, and how to prepare for the future of AD care.

Dementia treatment: A new dawn?

Acetylcholinesterase inhibitors and memantine have been the only available dementia treatments for around 25 years, but a deeper understanding of the underlying mechanisms of disease, is leading to a range of emerging therapies, said George. There are more 130 different drugs currently in development, and two, lecanemab and donanemab have been licensed by the Medicines and Healthcare products Regulatory Agency (MRHA). Questions regarding their clinical meaningfulness and cost effectiveness, however, mean they have not been approved by NICE.

“These drugs are probably the first stepping stone into mAbs,” said George. “There are multiple areas of concern and reasons why they are going to be tricky to manage. But there are lots more in development and they are likely to get cheaper, easier to deliver, and safer. We as clinicians need to understand these drugs, and get ready for them.”

The evidence

The CLARITY AD Phase III trial of lecanemab included 1,795 people with early Alzheimer’s disease (AD) recorded a 27% reduction in clinical decline, as measured by the Clinical Dementia Rating — Sum of Boxes (CDR-SB), a 37% slowing of clinical progression on the Alzheimer's Disease Assessment Scale Activities of Daily Living for Mild Cognitive Impairment (ADCS ADL-MCI) scale, and a 26% slowing of progression on the cognitive subscale Alzheimer's Disease Assessment Scale (ADAS-Cog), compared to placebo, at 18 months. A Phase III trial of donanemab in 1,182 people with mild AD found a 40% lower decline in ADL and a 39% lower risk of progressing to the next stage of disease, compared to placebo.

While the results are promising, George said there were still many unanswered questions regarding the use of these agents, including whether the affects are clinically meaningful to patients in their everyday lives. There are also challenges around reconfiguring services to deliver IV treatments and provide the necessary pre-treatment diagnostics, including lumbar puncture and PET, and MRI monitoring for potentially significant side effects, such as theamyloid-related imaging abnormalities (ARIA) that affected up to 25% of clinical trial participants.1,2 Costs, both in terms of the drugs themselves and of service redesign, are also an important consideration.

But delivering DMTs for AD will require the creation of services for people with mild cognitive impairment (MCI) – services that could benefit many more people than just those eligible for the drugs, said Iracema.

Health system preparedness for AD MDTs

Brain health interventions, such as lifestyle advice, cognitive and brain training, at this early stage can help to prevent progression, Iracema said, pointing to the 2024 Lancet Commission that identified 14 modifiable dementia risk factors, including high cholesterol and untreated vision loss. According to the document, addressing all modifiable risk factors could potentially prevent or delay 45% of dementia cases.

The Brain Health Clinic Blueprint, available via the Neurology Academy website, provides a step-by-step approach to setting up the services needed to identify, assess, and offer ongoing advice and care for MCI. It also sets out a patient journey that categorises people according to risk, and directs them to research, brain health management intervention, and monitoring according to their needs.

Such an infrastructure could create a foundation for DMT delivery, but there are still challenges around early detection, access to advanced medical facilities for diagnostic, delivery, and follow-up, and administration training. One approach to overcoming these barriers is the development of a conceptual framework for health system readiness, saidIracema, sharing an example from the infectious disease space that could be modified and applied to MCI. It is based on six core constructs, grouped into two categories:

1) System hardware: Material resources and structures

a) Surveillance: How to monitor the community to ensure people are identifiedearly enough to be eligible for treatment;

b) Infrastructure and medical supplies: Ensuring access to infusion, MRI, and CSF services

c) Workforce: Recruiting/training the necessary skills

d) Communication mechanisms: The most likely approach will be a hub and spoke model, with the hub being a more advanced medical centre, with the ability to deliver and monitor the drugs, and the spokes delivering ongoing treatment monitoring and holistic care. It is crucial to consider how different parts of the team will communicate

2) System software: Human and institutional relationships, values, and norms

a) Governance

b) Trust

“These constructs push us to think about what is necessary at every part of the pathway,” sad Iracema. Importantly, however, such services need to be equitable, and ensure that everyone who experiences MCI – not just those who are eligible for DMTS – can access the care they need. “We need to be thinking holistically about brain health clinics for these patients, not just in the context of medication,” she added.