Abstract
The emergence of the United States Food and Drug Administration (FDA)‐approved amyloid‐targeting therapies for Alzheimer's disease challenges clinicians and healthcare providers with a transformative landscape. Effectively communicating the risks, benefits, burdens, costs, and available support associated with these novel disease‐modifying treatments to patients, families, and other healthcare providers is essential but complex. In response, the Alzheimer's Association's Clinical Meaningfulness Workgroup has proposed language surrounding treatment eligibility, benefits, amyloid‐related imaging abnormalities (ARIA), apolipoprotein E (APOE) genotyping, and treatment costs, serving as a resource to healthcare professionals in navigating discussions with patients and their families. As the landscape evolves with the approval of new Alzheimer's therapies, this resource stands poised for updates, ensuring its continued relevance in facilitating informed and meaningful patient‐provider dialogues.
Highlights
Effective communication of risks, benefits, burdens, and costs of FDA‐approved amyloid‐targeting antibodies is essential to patients, families, and healthcare providers.
The Alzheimer's Association's Clinical Meaningfulness Workgroup provides language for physicians and healthcare providers around treatment eligibility, benefits, ARIA, APOE genotyping, and treatment costs.
This supplementary resource may be updated as new AD therapies become approved.
Keywords: Alzheimer's disease, amyloid targeting therapies, anti‐amyloid therapies, benefit, clinical meaningfulness, patient, patient‐care dyad, risk, treatment
1. INTRODUCTION
The United States Food and Drug Administration (FDA) approved two amyloid‐targeting monoclonal antibodies for the treatment of early‐symptomatic stage Alzheimer's disease (AD). 1 , 2 , 3 , 4 More recently, the United States Center for Medicare & Medicaid Services (CMS) provides patient coverage (under Coverage with Evidence Development) for these treatments, opening up a new landscape in AD diagnosis and care. These developments highlight the importance of equipping healthcare providers with resources about how to effectively engage in informative discussions with patients and their families regarding the benefits, risks, burdens, and costs, and available support associated with these FDA‐approved amyloid‐targeting therapies.
The Alzheimer's Association has been on the frontline of developing evidence‐based resources that help to explain the clinical meaningfulness of these FDA‐approved amyloid‐targeting therapies through the Clinical Meaningfulness Workgroup. This workgroup was formed in 2022, following discussions with the Alzheimer's Association's Research Roundtable, to discuss: (a) key considerations for interpreting data from cognitive and functional measures and (b) what is considered a clinically meaningful benefit or meaningful slowing of AD. Members of this Workgroup (Appendix A1) are experts in dementia care and research, dedicated to providing resources to clinicians to improve their understanding of and ability to communicate to patients and their families about what constitutes a clinically meaningful benefit in slowing AD's pathobiological and clinical progression. 5
Members of the Clinical Meaningfulness Workgroup convened in early 2023 to discuss best practices for healthcare providers in conversing with patients and their families about the benefits, risks, burdens, and costs associated with FDA‐approved amyloid‐targeting therapies. Based on learnings from the literature of oncology, which also faces challenges in communicating treatment options and adverse effects, 6 various topics were discussed with the goal of developing additional resources for clinicians, adjunct to materials already available. 7
Separately, the Alzheimer's Association's National Early‐Stage Advisory Group (ESAG), composed of individuals across the United States living with early‐stage AD, other dementias, or mild cognitive impairment (MCI), provided additional input and feedback. ESAG members were provided an early draft of the manuscript and supplied with overall comments and specific feedback on each section to ensure the representation of the patient's voice and perspective.
The workgroup also solicited input and feedback from three independent practicing clinicians (neurologist and geriatrician) who are actively diagnosing and treating patients with AD (S.N., H.R.O., and D.C.W.) and are not members of the Clinical Meaningfulness Workgroup.
Below are the key points that emerged from these discussions for consideration by healthcare professionals in navigating discussions with patients and families about FDA‐approved amyloid‐targeting therapies.
2. WHAT IS MOST IMPORTANT WHEN HAVING AN INTRODUCTORY DISCUSSION OF FDA‐APPROVED AMYLOID‐TARGETING THERAPIES WITH PATIENTS AND FAMILIES?
It is important to use appropriate language so that patients and families can understand delivered at a reasonable pace (i.e., not too fast) and personalized to the patient‐care partner dyad while remaining accurate and informative. Below are some suggestions on language use and points to consider:
2.1. Straightforward lay‐term language
Use language that avoids complex medical terminology, though judgment should be used depending on the background of the patient and care partner. Start with the basics of our current understanding of amyloid buildup in the brain and what the new treatments may offer. For example: “There's a protein building up in your brain, called amyloid, that is implicated in memory and thinking problems in AD. As the build‐up increases, brain cells are damaged and thinking difficulties often get worse, which can result in problems managing daily life and produce changes in personality along with behavioral symptoms. However, we now have new treatments that reduce brain amyloid and, in some people, can slow the progression of AD and the decline in memory, thinking, and functioning.”
2.2. Treatment eligibility and fit
Explain to patient and care partner dyads that the currently approved amyloid‐targeting therapies are recommended for patients in early symptomatic Alzheimer's disease (MCI or mild dementia due to AD). 8 , 9 Make sure they understand that patients, care partners, and healthcare providers together need to confirm: (a) the presence of amyloid plaques in the brain; (b) that persons with AD are in certain early clinical stages (i.e., MCI or mild AD dementia); and (c) that they do not have any medical conditions that would disqualify them from receiving infusion medications.
Furthermore, explain that these treatments may not be appropriate for every patient depending on factors including their unique medical history, social situation and family support, medication use, genetic background, and level of risk tolerance. To first determine their potential eligibility, they may have to undergo a set of diagnostic assessments, including “cognitive testing” and other studies, such as brain scans (magnetic resonance imaging [MRI], positron emission tomography [PET]), a lumbar puncture (“spinal tap”), and blood tests. Every patient and care partner is different, and certain pre‐requirements (e.g., genetic testing, brain imaging or spinal tap, and cognitive testing to stage the level of impairment) exist to determine their eligibility. Treatment eligibility for a disease‐slowing medication should also include an explanation of the importance of starting treatment early since delays translate to greater decline and there is no “catching up” as with symptomatic drugs.
RESEARCH IN CONTEXT
Systematic review: The Alzheimer's Association convened a workgroup of experts in dementia care and research to discuss best practices for healthcare providers in conversing with patients and their families about the benefits, risks, burdens, and costs associated with United States Food and Drug Administration (FDA)‐approved amyloid‐targeting therapies.
Interpretation: This paper serves as a supplementary resource for clinicians when having these discussions.
Future directions: As new Alzheimer's disease (AD) therapies become approved, we hope to build on this resource as needed to continue to improve communication among clinicians, patients, and their families.
2.3. Using visual aids
To make it easier for patients and families to understand the information, try incorporating images or videos that explain the disease, how it pathologically and clinically progresses, and how the new treatments work. Healthcare providers may utilize visual aids such as PET and MRI images to help illustrate their explanations, as well as graphics that depict the potential for clinical slowing (e.g., mitigating the trajectory of decline). For example, Figure 1 illustrates the concept of slowing decline in functional abilities over time (e.g., difficulty with employment, trouble managing finances, difficulty driving). The timing of these milestones will vary among those affected by AD; however, the orange line shows the impact of early intervention with a treatment that slows decline, which may result in “time saved” or a delay in these functional declines as a result of receiving treatment.
FIGURE 1.
Illustration of “time saved,” adapted from Petersen et al. 5
2.4. Positive language
Physicians often struggle to balance hope and candor when discussing and disclosing fatal diseases with patients and their families. To strike this balance, in both content and tone, it is important to use truthful, positive, and hopeful language about what these therapies may provide; while remaining factual regarding benefits that may be expected, in order to avoid unrealistic expectations. Providers should never use terms that imply, suggest, or may provide the expectation that these FDA‐approved amyloid‐targeting therapies improve memory and thinking or are a cure for AD.
2.5. Allow sufficient time
Even positive, simple language can be difficult to understand if rushed and delivered too quickly. When scheduling treatment conversations with the patient and family, healthcare providers should allow sufficient time for patients and care partners to absorb and appreciate the information being presented, ask questions, and sufficiently discuss the potential pros, cons, and alternatives. It may be helpful to have patients and care partners state essential information back to the clinician to ensure their understanding. As part of a patient‐centered dialogue, the length of these appointments may vary among patient‐care dyads, and it may be necessary to break and reconvene. A second or even third discussion may allow sufficient appreciation of the information.
2.6. Get to know your patient and caregiver
Understand who the patient and their caregiver are, as individuals, community members, and family. Learn about their fears, hopes, and priorities. For example, a 60‐year‐old patient who wants to provide for her family and is looking forward to a month‐long visit to Nepal will have very different priorities than an 82‐year‐old mourning his wife's recent passing and being taken care of by a harried mother of three. It is important to tailor approaches to meet the unique needs and circumstances of patients and families. Understanding the patient–caregiver dyad (and sometimes triad and beyond) is key to effectively communicating risks and appreciating the patient's risk tolerance.
3. WHAT LANGUAGE SHOULD BE USED TO DESCRIBE THE POTENTIAL BENEFITS OF THE FDA‐APPROVED AMYLOID TARGETING THERAPIES FOR PATIENTS AND FAMILIES?
It is important to use accurate, clear, concise, affirmative, and empowering language that provides an understanding of how these therapies may impact the patient's and caregiver's quality of life.
3.1. Using statistical terms
Statistical results and numbers from clinical trials may be difficult for some patients and families to comprehend. If citing statistics when discussing the benefits, adverse events, or risks of treatments, judgment should be used depending on the background of the patient and care partner. For example, explaining potential benefits in the context of “time saved” in lay terms often provides a more tangible understanding. For example, instead of focusing on a 30% slowing of progression on a scale that measures thinking and daily activities, talk about how much extra time is gained (e.g., 4–6 months over 18 months of treatment with the drug) and that patients may be able to retain certain abilities that are important for autonomy and independence. 5
3.2. Contextualize using patient‐centered real‐life examples
Use the patient's actual life experiences and interests to contextualize and explain what the benefits of these therapies may look like. For example, a patient could enjoy an additional 6 months at the early stages of the disease with loved ones and friends, while memories and functioning (e.g., shopping independently, and maintaining hobbies and cooking) are preserved, compared to no treatment. 5
3.3. Stay accurate and avoid giving false hopes
While using language, that is, affirmative, empowering, and conveys hope and optimism to patients and families, it is essential to stay accurate. Healthcare providers should not provide false hope to patients. These treatments are not a cure for AD and are not expected to reverse cognitive and functional deficits. It may be important to mention that the treatment may help some individuals but not others, such as those who have progressed to more advanced stages of AD.
3.4. What the future may look like
Explain to patients and families that, while current therapies are not a cure, the course of the disease may be changed. Treatment may provide more time, and there is mounting evidence that the benefits of disease‐slowing treatment may persist even after the treatment is discontinued, while other therapies are being developed. Amyloid‐targeting therapies are the start of a new era in AD treatment, and in the future, a combination of different therapies—and/or other new therapies—may be used to slow the progression of the disease even more. 9 Furthermore, as we continue to gain more experience on the long‐term effects of these FDA‐approved amyloid‐targeting therapies, we may be able to personalize dosing to the extent that we reduce treatment‐associated risks and burdens but maintain treatment efficacy. As the field learns how to individualize therapy, the latest plasma markers may help guide optimal long‐term treatment to maximize benefit, even after the treatment is discontinued.
3.5. Group benefit versus individual benefit
Inform patients and their caregivers that the results of clinical trials show the average benefit for a group of patients. In practice, we have noticed that some people may benefit more or less than others, and we are going to learn more in the future as more patients start taking these treatments.
4. WHAT ARE THE KEY THINGS TO DISCUSS WITH PATIENTS AND FAMILIES ABOUT THE RISKS OF FDA‐APPROVED AMYLOID‐TARGETING THERAPIES?
This conversation should include the risks involved, such as infusion‐related reactions and amyloid‐related imaging abnormalities (ARIA); how these risks can be detected, monitored, and managed; who is at a higher risk of adverse events; and what they mean in the context of treatment benefits. Patients should be provided a specific Medication Guide for approved treatments, which provides important information that patients should know about the treatment.
4.1. Infusion‐related reactions
Note to patients that there is about a 1 in 4 chance of developing infusion‐related reactions, which are generally mild and can be medically managed.
4.2. Explain what ARIA is
Use simple terms to describe different types of ARIA including ARIA‐E (edema) and ARIA‐H (hemorrhage); for example, “areas of fluid buildup” in the brain or “temporary swelling in areas of the brain that usually resolves over time” can be used to refer to ARIA‐E, and “bleeding in the brain that is usually limited to very small spots” can be used to refer to ARIA‐H. Another example to describe ARIA monitoring is: “There's a chance of developing an accumulation of fluid and/or small spots of blood in the brain that may be symptomatic or not, but we will follow it over time with brain scans reviewed by radiologists.”
4.3. Symptomatic versus asymptomatic
Patients and families need to understand that, while the majority of ARIAs are asymptomatic, there are symptomatic cases that may require urgent evaluation, additional brain scans, dose adjustment, monitoring, management, or discontinuation of therapy. Uncommonly, serious adverse events may require hospitalization and management or may lead to further impairment; and rarely, large brain swelling and/or bleeding, seizures, and deaths have occurred.
4.4. How often ARIAs occur
Rates and timing of ARIA may vary among treatments. It is helpful to explain the rate in simple terms, such as 2 in 10 people who received lecanemab developed brain changes such as small spots of bleeding in the brain temporary swelling in brain areas, or a combination of the two. It is important to differentiate between “average” occurrence rates and personalize wherever appropriate (e.g., if the patient is apolipoprotein E4 [APOE4] heterozygous then your risk is higher).
4.5. Monitoring and early detection
Highlight the requirement for surveillance, including reporting of symptoms and regular MRI, and the importance of early detection of ARIA. Emphasize to patients and care partners that, if we detect ARIA early, we can closely monitor the situation and take appropriate measures, including temporarily pausing infusions to allow natural stabilization or resolution, and, in some circumstances, provide additional monitoring or treatment as necessary. Common symptoms of ARIA may mimic stroke and include headache, confusion, vomiting, visual or gait disturbance, dizziness, nausea, tremors, and changes in mental state.
4.6. Use standard processes, workflows, and protocols
Advise the patient and family that there is an established protocol in place to handle any potential adverse events. Explaining these standardized processes, workflows, and protocols will help patients and families to better understand the process and that their safety is important.
To facilitate effective detection and monitoring for ARIA, it may be helpful to utilize electronic and health record reminders, implement check and balance processes, and establish checklists to gather and harmonize critical information before and after each infusion and/or MRI monitoring scan.
4.7. Unknowns regarding potential benefits and risks for underrepresented populations
Explain to patients and care partners that the current benefits and risks for specific underrepresented populations are unknown and further research is ongoing. While APOE testing is not required, APOE genotyping helps in assessing benefit‐risk considerations. People who carry a specific gene version called APOE4 have a higher risk of ARIA side effects. It is unknown if underrepresented populations have a similar risk.
5. WHAT IS IMPORTANT TO DISCUSS WITH PATIENTS AND FAMILIES REGARDING THE BURDENS, COSTS, AND FINANCIAL IMPLICATIONS OR LOGISTICAL COMMITMENTS OF TAKING FDA‐APPROVED AMYLOID‐TARGETING THERAPIES?
Patients and families need to be provided with clear information about the costs and logistical commitments of taking FDA‐approved AD therapies, including unknowns. Ideally, a team member(s) should be dedicated to discussing the costs and logistics with patients and their families and addressing any questions or concerns they may have.
5.1. Insurance coverage type
The costs and logistics depend on the patient's insurance type and individual practice requirements. Explain which aspects of treatment are covered by insurance and the potential out‐of‐pocket costs. Encourage patient‐care partner dyads to contact their insurance provider directly to better understand all costs involved while offering your help and support. It is important to inform patients and care partners that the CMS requires patients and care partners to enroll in a registry, either the Medicare registry or the ALZ‐NET registry (Alzheimer's Network for Treatment and Diagnostics) so that more information can be acquired about treatment effectiveness and side effects.
5.2. Conversations on required commitments
It is important to talk about all the required commitments for both the patient and care partner that will be necessary throughout the treatment process, such as the need for regular medical appointments, screening (e.g., cerebrospinal fluid, PET, and APOE), and monitoring (e.g., MRI, and PET), as well as accessibility to infusion centers. At this time, there is no definitive answer on how long someone needs to be treated with amyloid targeting therapy for AD, but treatment may stop if amyloid levels are substantially reduced. 10
5.3. Challenges in the accessibility of infusion centers
Conversations will depend on whether the infusion center is in‐house or is provided by external facilities. Access to external infusion centers may be challenging, especially for those living in rural areas, and may limit regular contact between physicians and patients. Once safety is established after several months of treatment, you may suggest in‐home infusions, if this option is available, for those with limited access to infusion centers.
TABLE 1.
Key points to consider for healthcare providers in navigating discussions with patients about FDA‐approved amyloid‐targeting therapies for AD.
| Discussion phase | Examples of language use and key points to consider for healthcare providers |
|---|---|
| Introductory discussion | |
| AD and new treatments | “There's a protein that has built up in your brain that causes memory and thinking problems. It may get worse over time, but we now have a treatment that slows this progression in some people.” |
| Treatment eligibility | “We need to determine your eligibility using a set of diagnostic tests such as a brain scan or spinal tap.” |
| Treatment fit | “Even if eligible, these treatments may not be a good fit for every patient. Every patient is different, and treatment fit depends on factors such as past medical history, genetic background, and level of risk tolerance.” |
| Using visual aids | Use visual aids such as MRI and PET to show amyloid buildup and ARIA. |
| Sufficient Time | Allow time for patients and families to absorb information and have a Q&A. |
| Positive language | Use affirmative, empowering, and positive language while avoiding giving false hopes. |
| Discussion of benefits | |
| Time saved vs. statistical terms | Instead of mentioning a 30% slowing decrease in the CDR‐SB score, talk about the amount of extra time patients could spend keeping their autonomy and independence. In 18 months of treatment, 4–6 months could be added due to treatment for the time when people maintain their autonomy and independence. |
| Contextualize by using a patient‐centered real‐life example | Patients could enjoy an additional 4–6 months with their loved ones and friends and have more time living independently. |
| Not giving false hopes | These treatments are not a cure for AD and will not improve symptoms or reverse changes. These treatments may not work for every patient. |
| Future perspective | The new treatments are the start of a new era in AD treatment, and in the near future, a combination of different therapies may be used to slow the progression even more. We are also continuing to learn how to better personalize the use of these medications. |
| Group benefit vs. individual benefit | Clinical trial results are average results for a group of patients. In practice, there are some people who get more benefits than others. |
| Discussion of risks | Risks, including infusion reactions and ARIA, are in the majority of situations mild, temporary, and manageable; however, uncommonly they can be serious and result in disability or death. Patients should be provided with the specific Medication Guide for approved treatments, which provides important information that patients should know about the treatment. |
| Infusion‐related reactions | Can be serious but are usually mild and manageable. |
| ARIA‐E | “Fluid buildup in the brain”; “temporary swelling in areas of the brain that usually resolves over time”; “temporary accumulation of fluid in the brain.” |
| ARIA‐H | “Small spots of bleeding in the brain”; “small accumulations of blood in the brain.” |
| Symptomatic vs. asymptomatic ARIA |
“There's a chance of developing an accumulation of fluid or small spots of blood in the brain that may be symptomatic or not, but we will follow it over time with trained radiologists.” or “While the majority of cases are asymptomatic, there are symptomatic cases that may require dose adjustment, monitoring, management, or discontinuation of therapy.” |
| Monitoring and early detection | “If we detect ARIAs early, we can closely monitor the situation and provide appropriate treatment when necessary.” |
| Use standard protocol | Use the same protocol among team members. |
| Risk for underrepresented population |
Certain patient populations were underrepresented in clinical trials. As more underrepresented individuals receive treatment, we will learn more and potentially move the science forward for all who may benefit from these treatments. “Your participation can help move the science forward for all who may benefit from these treatments” |
| Financial and logistics discussion | |
| Type of insurance coverage | Medicare vs. private insurance |
| Logistical conversation | Need for frequent travel to the infusion center and monitoring centers. |
| Accessibility | Access to infusion centers for rural area residents is limited. Once safety is established, at‐home infusions may be offered. |
| APOE genotype | |
| Set the stage and context | Be sensitive, empathic, and clear. Explain the relevance of the APOE genotype to adverse events. |
| Explain what is “APOE” | Explain the link between APOE and AD risk, different APOE alleles, the impact of APOE alleles on AD risk in different populations, and the risk of developing adverse events depending on the APOE genotype. |
| Risk of ARIA according to APOE | “People with a certain APOE genotype have a higher risk of developing adverse events from these treatments, such as temporary fluid accumulation or small spots of blood in the brain.” |
| Familial consequences | Emphasize the importance of family discussion. |
| Difference between APOE and other familial AD | Having the APOE ε4 allele does not necessarily result in the development of AD, and it is one of the many AD risk factors. |
Abbreviations: AD, Alzheimer's disease; APOE, apolipoprotein E; ARIA, amyloid‐related imaging abnormalities; ARIA‐E, amyloid‐related imaging abnormalities ‐ edema; ARIA‐H, amyloid‐related imaging abnormalities ‐ hemorrhage; CDR‐SB, Clinical Dementia Rating Scale – Sum of Boxes; FDA, United States Food and Drug Administration; MRI, magnetic resonance imaging; PET, positron emission tomography; Q&A, question and answer (session).
6. HOW TO DISCUSS APOE‐GENOTYPING INFORMATION WITH PATIENTS AND FAMILIES?
Healthcare providers should be sensitive, empathic, and clear when discussing the important implications (both for the patient and family), of APOE genotype and address any questions they may have.
6.1. Establish the context
Set the stage by explaining to patients that APOE genotyping is primarily for risk assessment for ARIA and that having a certain genotype may increase the likelihood of adverse events.
6.2. Explain “APOE” by clarifying the following points in lay terms 8 , 11 , 12 , 13 , 14 , 15
APOE protein function, and its role in diseases (e.g., lipid metabolism, cardiovascular disease, and AD).
Different APOE gene variants/alleles (e.g., ε3/ε3, ε2/ε4, ε4/ε4).
The link between APOE and AD risk.
The impact of APOE alleles on risk in different populations.
Risk of developing adverse outcomes (i.e., ARIA‐E) depending on the patient's APOE genotype.
Emphasize that having the APOE ε4 allele does not necessarily result in the development of AD symptoms, and it is one of many AD risk factors.
Discuss potential implications for the patient and family (medical, psychological, financial/long‐term care coverage).
6.3. Rate of adverse outcomes depending on APOE genotypes
APOE4 carriers are more susceptible to developing ARIA. This side effect can potentially recur, and be more severe, symptomatic, and serious, particularly if patients carry two copies of the ε4 allele. 16 , 17
6.4. Familial consequences
Describe how this information may impact their family members and the importance of family discussion. Explain the difference between the APOE gene and other rare genetic mutations that cause familial AD.
7. SUMMARY
The advent of FDA‐approved amyloid‐targeting therapies for Alzheimer's disease is important and exciting, though it provides challenges to physicians and healthcare providers on how to accurately describe the risks, benefits, burdens, costs, and available support associated with these new disease‐modifying treatments. The members of the Alzheimer's Association's Clinical Meaningfulness Workgroup, ESAG, and a trio of clinicians provided suggestions on how to communicate the risks and benefits using simplified terms, summarized in Table 1. Standardizing language around treatment eligibility, benefits, ARIA, APOE genotyping, and treatment cost will potentially avoid communicating inaccurate information and unrealistic expectations. This paper serves as a supplementary resource for physicians and healthcare providers when having these discussions. As new AD therapies are approved, there may be different risks and expectations. Our goal is to update this resource to facilitate those discussions, as needed.
CONFLICT OF INTEREST STATEMENT
A.A. has received honoraria or support for consulting; participating in independent data safety monitoring boards; providing educational lectures, programs, and materials; or serving on advisory or oversight boards for AbbVie, Acadia, Allergan, the Alzheimer's Association, Alzheimer's Disease International, Axovant, AZ Therapies, Biogen, Eisai, Grifols, Harvard Medical School Graduate Continuing Education, JOMDD, Life Molecular Imaging, Lundbeck, Merck, Prothena, Roche/Genentech, Novo Nordisk, Qynapse, Sunovion, Suven, and Synexus. A.A. receives book royalties from Oxford University Press for a medical book on dementia. A.A. receives institutional research grant/contract funding from NIA/NIH 1P30AG072980, NIA/NIH U22AG057437, AZ DHS CTR040636, Washington University St Louis, and Gates Ventures. A.A.’s institution receives/received funding for clinical trial grants, contracts and projects from government, consortia, foundations and companies for which he serves/served as contracted site‐PI. Of special note, A.A. currently serves as site‐PI for the AHEAD 3‐45 study (lecanemab for secondary AD prevention); and previously served as site‐PI for the A4 study (solanezumab for secondary AD prevention), as site‐PI (at his previous institution) for the Biogen EMERGE study (aducanumab for early‐AD treatment), and as Project Arm Leader for the DIAN‐TU Gantenerumab study. PSA has received grants or contracts to support research from the NIH, Alzheimer's Association, FNIH, Lilly, Janssen, and Eisai, and has received consultant fees from Merck, Biogen, Abbvie, Roche, Immunobrain Checkpoint. D.S.M. is a full‐time employee and shareholder of Signant Health. RCP is a full‐time employee of Mayo Foundation for Education and Research, a consultant for Roche, Inc., Nestle, Eli Lilly & Co., Genentech Inc. (including DSMB), and Eisai, Inc., and has received grant funding from NIA ADRC, MCSA, ADNI, ACTC, MarkVCID. D.M.R. has received consulting fees from the Dana Foundation. S.M., C.J.W. and M.C.C. are full‐time employees of the Alzheimer's Association. J.H. is a full‐time employee of Acumen, has received consulting fees from Washington University Dominantly Inherited Alzheimer Network Trials Unit (DIAN‐TU), and is a stockholder for Acumen and Eli Lilly. E.R.S. is full‐time employees of Acumen, and has received consulting fees from Cogstate Ltd., Cortexyme Inc., Partner Therapeutics Inc., Vaccinex Inc., Gates Ventures LLC, Hoffman La Roche Ltd, US Green Valley Pharmaceuticals Inc., has participated on a DMSB for Hoffman La Roche Ltd, has been an unpaid consultant and unpaid board of directors member for the Alzheimer's Association and Bright Focus Foundation, respectively, and is a stockholder for Acumen and Eli Lilly. M.I. is a full‐time employee of Eisai, Inc. J.L. was a full‐time employee of Biogen and Biogen stockholder at the time of manuscript creation/submission. B.R.M. is a full‐time employee and shareholder of Eli Lilly & Co. SN has received payment or honoraria from Eisai, Biogen, Serono, and TG Therapeutics. HO has received compensation from Biogen & Eisai (salary support), and Biogen & Optina Diagnostics (consulting fees to Eastern Virginia Medical School). D.C.W. has received grants or contracts from ATRI, Eisai, ATRI, Cognition, Acumen, Cerevel, Sage, Acadia, Alzheimer's Association, Alzheon, Lilly, Roche, Serono, Sanofi, received payment or honoraria from AAN, Eisai, and Lilly, and has participated in DSMBs for Biogen, Eisai, Novartis, FDA, Maplight, and VizAI. Author disclosures are available in the Supporting Information.
Supporting information
Supporting Information
ACKNOWLEDGMENTS
This article was facilitated by the Alzheimer's Association Clinical Meaningfulness Workgroup, which brought together stakeholders from industry, academia, the clinical community, and the Alzheimer's Association. The views and opinions expressed represent those of the authors and Clinical Meaningfulness Work Group members (Appendix A) involved in this publication and do not necessarily reflect those of the organizations at which individuals are employed. As a participating member of the broader working group, Roche contributed to the review of this paper. The Workgroup thanks the Alzheimer's Association's Early Stage Advisory Group (ESAG) for their valuable input and contributions to this paper, including Richard (Dick) Smith, Myra Solano Garcia, Donna Arnold, and Tony Gonzales. The Workgroup also thanks Dr. Okhravi, Dr. Napoli, and Dr. Weisman for their clinician perspectives, drawing on collective years of clinical experience, coordination, and communication of care among their patients and families. This manuscript did not receive any specific grant from funding agencies in the public, commercial, or not‐for‐profit sectors.
APPENDIX A. COLLABORATORS
A.1.
Alzheimer's Association Clinical Meaningfulness Workgroup Members and Collaborators.
| Name | Affiliation |
|---|---|
| Paul Stephen Aisen, MD | University of Southern California |
| J. Scott Andrews, PhD | Takeda Pharmaceuticals |
| Alireza Atri, MD, PhD | Banner Sun Health Research Institute |
| Janice Hitchcock, PhD | Acumen Pharmaceuticals, Inc. |
| Michael C. Irizarry, MD, MPH | Eisai Ltd. |
| Jaren Landen, PhD | Biogen |
| Claire Lansdall, PhD | Roche Products Ltd. |
| Brandy R. Matthews, MD, FAAN | Eli Lilly and Company |
| David S. Miller, MD, MA | Signant Health |
| Ronald Petersen, MD, PhD | Mayo Clinic |
| Dorene Rentz, PsyD | Brigham and Women's Hospital |
| Eric Siemers, MD | Acumen Pharmaceuticals, Inc. |
| Maria Carrillo, PhD | Alzheimer's Association |
| Christopher Weber, PhD | Alzheimer's Association |
Rentz DM, Aisen PS, Atri A, et al. Benefits and risks of FDA‐approved amyloid‐targeting antibodies for treatment of early Alzheimer's disease: Navigating clinician‐patient engagement. Alzheimer's Dement. 2024;20:8162–8171. 10.1002/alz.14199
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