Equitable Access to Alzheimer’s Disease Therapeutics for Adults with Down Syndrome
by Matthew P. Janicki, Ph.D., Hampus Hillerstrom, and Richard Fisher, Ph.D.
Don is living with Down Syndrome in Colorado. Photo Credit: Rick Guidotti for Positive Exposure.
Adults with Down syndrome face a heightened risk of developing Alzheimer's disease (AD) at an earlier age compared to the general population. With a cumulative risk of Down syndrome associated with Alzheimer's dementia (DS-AD) reaching 50% by their mid-50s, it is crucial for this vulnerable group to have timely access to the emerging class of anti-amyloid Alzheimer's disease immunotherapeutics, including lecanemab and donanemab. However, current prior authorization prescribing criteria for these treatments fail to consider inclusion parameters unique to adults with Down syndrome, thereby creating barriers to equitable care. To address this issue, under the leadership of the NTG and the Lumind IDSC Foundation, a multinational working group of experts convened to examine and propose necessary adaptations to prescribing criteria, ensuring that adults with Down syndrome qualify to benefit from the new class of disease-modifying drugs, anti-amyloid immunotherapies.
This article explores the key findings and recommendations put forth by the Working Group on Criteria for Access to Alzheimer's Therapeutics for Adults with Down Syndrome. Its report can be found at https://www.the-ntg.org/lumind-drug-equivalency.
Existing Criteria and the Need for Adaptation
Current prior authorization prescribing criteria for new AD immunotherapies in the United States, developed for the general population with mild cognitive impairment (MCI) or mild AD dementia, are inconsistent and do not account for the unique needs of adults with Down syndrome. The criteria primarily focus on minimum age, exclusion of non-Alzheimer's causes of dementia, cognitive decline assessment, and biomarker indicators for brain amyloid plaques. Some criteria specifically exclude individuals with Down syndrome due to pre-existing cognitive impairments. Additionally, the use of neurocognitive measures designed for the general population are inadequate for assessing cognitive decline in individuals with Down syndrome. The current FDA label and state prior authorization criteria for specific therapies vary in their inclusion and assessment of individuals with a history of intellectual disability, including adults with Down syndrome. Some state criteria explicitly exclude adults with Down syndrome, while others are silent on the inclusion of populations with developmental or neuropsychiatric conditions.
Proposed Wording Adaptations
The working group produced a report that recommends alternative inclusionary wording for state drug formulary committees to ensure the equitable inclusion of adults with Down syndrome. The proposed adaptations aim to establish equivalencies between DS-AD and sporadic AD patients, enabling access to anti-amyloid immunotherapeutics. The adaptations emphasize the unique cognitive phenotype of Down syndrome and advocate for the use of validated screening measures and directly administered tests suitable for adults with lifelong cognitive impairments. In assessing cognitive impairment in adults with Down syndrome, the current assessments used for sporadic AD may not be effective in quantifying cognitive decline against a background of pre-existing intellectual impairments.
Medically Complex
“…many adults with Down syndrome have co-occurring conditions, the treatments for these conditions should be monitored for any negative effects on behavior and function.”
Therefore, alternative methods specifically adapted for adults with Down syndrome are necessary. These methods involve gathering information from the adults themselves and their caregivers, assessing physical and mental health, and using various tests to measure functional capacities and signs of cognitive decline. Physicians should also conduct full clinical workups and medication reviews to identify any treatable causes for decline. Additionally, as many adults with Down syndrome have co-occurring conditions, the treatments for these conditions should be monitored for any negative effects on behavior and function.
Training and Resources
Recognizing the limited number of experts in DS-AD, the working group suggests that governmental entities and academic health institutions offer education and continuing education programs for prescribers to assess adults with neuroatypical conditions, including those at high risk of amyloid build-up like adults with Down syndrome. Nonprofits and professional organizations are encouraged to develop technical resources that can provide guidance on assessment scale instruments and clinical work-ups specific to Down syndrome. The group also called for training in cognitive testing for adults with Down syndrome to increase the number of capable clinicians and prescribers.
Addressing Urgency
The working group emphasizes the urgency in adapting state prior authorization prescribing criteria to prevent delays in access to treatment for adults with Down syndrome. The compressed aging factor in this population and the potential benefits of early treatment necessitate immediate action. Waiting for safety data before making formulary changes would deprive adults with Down syndrome of potentially beneficial therapeutics during their limited remaining years of life. The group urges state drug formulary committees to review the recommendations promptly and incorporate them into existing criteria.
Urgent Situation
“The compressed aging factor in this population and the potential benefits of early treatment necessitate immediate action.”
Safety Considerations
While advocating for access to amyloid-targeting immunotherapies, the working group acknowledges the need for safety data specifically for adults with Down syndrome. Concerns regarding cerebral amyloid angiopathy and potential side effects necessitate clinical safety studies before administering such immunotherapies to this population. The group aligns with the appropriate use criteria for Aduhelm™ and Leqembi™, recommending not treating people with Down syndrome until sufficient safety data are available. However, as the Centers for Medicare and Medicaid Services (CMS) approved coverage for Leqembi for all patients enrolled in a patient registry who meet CMS inclusion criteria , the Group recommends that registry entry criteria be adapted to include adults with Down syndrome.
Recommendations for Improving Access
To ensure equitable access to anti-amyloid immunotherapies, the working group proposes several recommendations. These include sharing the adaptations with all stakeholders involved in the availability of FDA-approved disease-modifying therapies, establishing a standing advisory group for ongoing refinement of criteria, providing guidance to primary care physicians on meeting prescribing criteria, and promoting greater awareness and education among healthcare professionals on the evaluation and treatment of adults with Down syndrome.
Conclusion
The efforts of the multinational working group have highlighted the disparities in access to Alzheimer's disease therapeutics for adults with Down syndrome. By proposing adaptations to current prescribing criteria, healthcare professionals can ensure that this high-risk population receives equitable treatment options. Urgency for action is crucial to prevent further delays in accessing potentially life-changing therapies to a population with uniquely high Alzheimer’s disease risk. Safety considerations and the need for research highlight the importance of ongoing studies and comprehensive monitoring. With concerted efforts, adults with Down syndrome can gain access to emerging anti-amyloid immunotherapies, enhancing their quality of life while delaying death due to Alzheimer’s dementia.
Authors
Matthew P. Janicki, PhD., is an associate researcher professor at the Department of Disability and Human Development at the University of Illinois Chicago and is the Co-President of the Board of the National Task Group on Intellectual Disabilities and Dementia Practices (Rockport, ME).
Hampus Hillerstrom is CEO of the LuMind IDSC Down Syndrome Foundation (Burlington, MA).
Richard Fisher, Ph.D., is the Chief Scientific Officer at the LuMind IDSC Down Syndrome Foundation (Burlington, MA)