From the Guidelines
Anti-amyloid monoclonal antibody treatments for Alzheimer's disease are associated with immune-related adverse effects, primarily ARIA (Amyloid-Related Imaging Abnormalities), which includes ARIA-E (edema/effusion) and ARIA-H (microhemorrhages and hemosiderosis), occurring in approximately 20-40% of patients, as reported in studies such as 1 and 1. The incidence of these adverse effects varies by drug, with rates of ARIA-E ranging from 13-17% for lecanemab to 35% for aducanumab, and 24-37% for donanemab, as observed in clinical trials 1. Most cases of ARIA are asymptomatic and detected only on MRI, but when symptomatic, patients may experience headache, confusion, dizziness, visual disturbances, or nausea, highlighting the need for regular MRI monitoring during treatment, particularly in the first months when ARIA risk is highest 1. Key risk factors for ARIA include APOE ε4 gene carrier status, with homozygous carriers having 2-3 times higher risk than non-carriers, as noted in studies examining the genetic predisposition to these adverse effects 1. Other immune-related adverse effects of anti-amyloid monoclonal antibodies include infusion-related reactions, which are reported in 20-40% of patients and typically present as flu-like symptoms, headache, nausea, and skin reactions, underscoring the importance of careful patient monitoring and management of these potential side effects 1. The mechanism behind these adverse effects involves the binding of monoclonal antibodies to amyloid plaques, triggering immune-mediated clearance, which can lead to the development of ARIA and other immune-related adverse effects, as explained in the context of amyloid-modifying therapies 1.
Some of the key points to consider when evaluating the immune-related adverse effects of anti-amyloid monoclonal antibody treatments include:
- The incidence and severity of ARIA, including ARIA-E and ARIA-H, and their association with specific drugs and patient risk factors
- The importance of regular MRI monitoring during treatment to detect asymptomatic cases of ARIA and to manage symptomatic cases promptly
- The need for careful patient monitoring and management of infusion-related reactions and other immune-related adverse effects
- The role of APOE ε4 gene carrier status in predisposing patients to ARIA and other adverse effects
- The mechanism of action of anti-amyloid monoclonal antibodies and their potential impact on amyloid clearance and immune-mediated responses.
Overall, the immune-related adverse effects of anti-amyloid monoclonal antibody treatments for Alzheimer's disease are a significant concern, and careful patient monitoring, management, and education are essential to minimize their impact and optimize treatment outcomes, as supported by the evidence from studies such as 1 and 1.
From the Research
Immune-Related Adverse Effects of Anti-Amyloid Monoclonal Treatment
- The type of immune-related adverse effects associated with anti-amyloid monoclonal treatment for Alzheimer's disease include amyloid-related imaging abnormalities (ARIA) with edema or effusions (ARIA-E) and ARIA with cerebral microhemorrhages, cerebral macrohemorrhages, or superficial siderosis (ARIA-H) 2, 3, 4.
- Infusion reactions also occur and require anticipatory management 2, 4.
- The incidence of ARIA-E and ARIA-H is higher in patients treated with FDA-approved anti-amyloid monoclonal antibodies compared to those receiving placebo 3.
- The exact incidence of immune-related adverse effects varies depending on the specific monoclonal antibody used, with aducanumab, lecanemab, and donanemab having different profiles of administration, titration, amyloid target, and adverse events 2, 5.
Management and Monitoring of Adverse Effects
- Monitoring and management of ARIA and infusion reactions are crucial to prevent serious or rare catastrophic consequences 2, 4.
- Close monitoring of patients during the period of treatment initiation is necessary to detect the occurrence of ARIA and infusion reactions 4.
- The development of subcutaneous formulations and the use of blood-based biomarkers for diagnosis and monitoring may increase the accessibility and decrease the demands on healthcare systems associated with these agents 2.