What are the specific risks and monitoring requirements for patients receiving lecanemab or donanemab?
Executive summary
Two monoclonal antibodies—lecanemab (Leqembi) and donanemab (Kisunla)—offer modest slowing of early Alzheimer’s symptoms but carry specific, sometimes serious safety risks that require structured monitoring: chiefly brain swelling and bleeding known collectively as ARIA, infusion reactions, and laboratory abnormalities; both drugs require baseline and repeated MRIs and other checks during treatment [1] [2] [3]. Clinics and guideline documents emphasize patient selection (including APOE genotyping), informed consent about harms and benefits, and protocols for MRI surveillance, infusion observation, and blood testing [3] [1] [4].
1. What the main risks are — ARIA (brain swelling and microhemorrhages) is central
The dominant, well-documented toxicity for both agents is amyloid‑related imaging abnormalities (ARIA), manifesting as leakage of blood vessels (microhemorrhages) and brain swelling; trials reported ARIA rates substantially higher than placebo and more frequent and severe with donanemab than lecanemab, with symptomatic ARIA producing headaches, visual changes, confusion and, rarely, life‑threatening events [5] [2] [6].
2. Infusion-related reactions and acute risks during administration
Both drugs are delivered intravenously and can provoke infusion‑related reactions—fever, chills, nausea, flushing, shortness of breath or chest discomfort—typically during or within 30 minutes after infusion; these reactions occurred in clinical experience and the donanemab label flags immediate post‑infusion symptoms, with centers observing patients after each dose [4] [7] [8].
3. Bloodwork and laboratory monitoring requirements
Safety protocols include baseline and periodic laboratory testing because lecanemab was associated with transient hematologic changes—about 40% had temporary lymphocyte decreases and 20% increases in neutrophils—and both centers and package recommendations call for blood monitoring to detect treatment‑related changes or contraindications [4] [3].
4. MRI surveillance: frequency, purpose, and eligibility limits
MRI is the central surveillance tool: patients must have a screening MRI within 12 months before initiation to establish baseline risk and then undergo frequent MRIs during treatment to detect ARIA early; those unable to undergo MRI (e.g., pacemaker, claustrophobia, metal implants) are typically excluded from therapy because monitoring is integral to safe use [3] [4] [9].
5. Patient selection: APOE genotype, anticoagulation, and stage of disease
Guidance and major centers restrict use to people with early symptomatic Alzheimer’s and require confirmation of amyloid pathology; APOE ε4 homozygotes appear to have higher ARIA risk and many centers will not recommend treatment for patients with two copies of ε4, while patients on blood thinners are at increased risk of symptomatic brain bleed and are often excluded [1] [9].
6. Practical workflow: infusion schedule, observation, and follow‑up
Lecanemab is given every two weeks and donanemab typically every four weeks at supervised infusion centers; institutions describe observation periods after each infusion, periodic phone symptom checks, and additional MRIs if new symptoms arise—reflecting an intensive, ongoing safety workflow that adds time and cost beyond the drug itself [1] [8] [10].
7. Comparative and unresolved concerns: higher ARIA with donanemab, small clinical benefits
Data syntheses and institutional reports suggest donanemab may clear amyloid faster and show somewhat larger trial effects but also a higher incidence of ARIA and bleeding than lecanemab; at the same time, the absolute clinical benefit over 18 months is modest, and adverse events including symptomatic ARIA may have influenced trial unblinding—issues noted in independent analyses and reviews [11] [12] [5].
Conclusion
Lecanemab and donanemab require carefully selected patients, informed consent about modest benefit and nontrivial risks (especially ARIA and infusion reactions), baseline APOE/genetic and MRI assessment, routine blood tests, scheduled MRIs during therapy, post‑infusion observation, and protocols to pause or stop treatment if ARIA or serious reactions occur; guidance documents and major centers explicitly build these monitoring steps into clinical pathways, and uncertainty remains about long‑term tradeoffs between modest clinical slowing and potential for serious brain injury [3] [8] [2].