What are the common side effects and monitoring requirements for lecanemab and donanemab?
Executive summary
Lecanemab and donanemab are monoclonal anti‑amyloid antibodies approved for early Alzheimer’s disease that produce modest slowing of decline but carry important and common safety risks—most notably amyloid‑related imaging abnormalities (ARIA), infusion reactions, and laboratory changes—that require protocolized monitoring including baseline and serial brain MRI and blood tests [1] [2] [3]. Donanemab appears to have higher rates of ARIA in trials than lecanemab, and both drugs carry amplified risk in people with two copies of the APOE ε4 gene and in those taking anticoagulants, leading many centers to exclude those groups from treatment [4] [5] [6].
1. How these drugs cause the common side effects: ARIA explained
Both agents remove amyloid from brain tissue, and that process can destabilize amyloid within vessel walls or parenchyma, producing swelling (ARIA‑E) and microhemorrhages or larger bleeds (ARIA‑H); clinical trial reports and institutional FAQs list ARIA—brain swelling and bleeding—as the single most common and most serious shared side effect of lecanemab and donanemab [7] [8] [1]. Trial‑level incidence varied: lecanemab symptomatic ARIA occurred in a notable minority and overall ARIA rates were lower than donanemab’s, whereas donanemab’s trials reported higher rates of both ARIA‑E and ARIA‑H, with some series showing brain swelling in roughly 24% and bleeding in about 31% of participants versus roughly 13% and 17% for lecanemab respectively in other reports [4] [3] [1].
2. Other common adverse events: infusion reactions and lab changes
Infusion‑related reactions—fever, chills, myalgias and other flu‑like symptoms—were commonly reported during or shortly after dosing, particularly with donanemab where reactions occurred in about 10% of patients during or within 30 minutes of infusion; lecanemab also produces infusion reactions and has been associated with transient hematologic changes such as decreased lymphocytes (≈40%) and increased neutrophils (≈20%), prompting routine laboratory monitoring [9] [10] [2]. Serious allergic reactions are listed as possible with lecanemab and were accounted among the safety considerations in regulatory and clinical guidance [2].
3. Who is at higher risk and exclusions used by clinics
Multiple centers and regulatory documents flag APOE ε4 homozygotes and patients on anticoagulants as higher‑risk populations: clinical programs state they will not recommend therapy for patients with two copies of APOE ε4 and will generally exclude people on blood thinners due to greater symptomatic bleed risk [5] [6]. Cerebral amyloid angiopathy and other vascular vulnerability were also cited as contraindications or reasons for exclusion, reflecting trial criteria and post‑trial clinical caution [6] [11].
4. Monitoring requirements used in trials and adopted in practice
Monitoring protocols require baseline confirmation of Alzheimer pathology (amyloid PET or CSF) and baseline brain MRI before treatment, then serial MRIs during therapy to detect ARIA early—frequency varies by protocol but clinics emphasize repeat MRI checks and additional MRIs for any new symptoms [12] [13] [7]. Infusions include immediate post‑infusion observation periods to watch for acute reactions, and programs typically perform periodic symptom calls and laboratory blood tests to track hematologic changes and safety [13] [9].
5. Practical implications: cost, logistics and resource strain
Beyond clinical risk, implementing these agents demands frequent visits for infusions (lecanemab every two weeks; donanemab monthly), MRI capacity for serial imaging, infusion observation infrastructure, and lab monitoring—costs and system strain are nontrivial and were highlighted by academic centers warning that MRI monitoring and infusion logistics increase the overall burden beyond the drug list price [5] [13] [12].
6. Evidence caveats and the balance clinicians must strike
Clinical trials show modest average clinical benefit but clear safety trade‑offs: reviewers note small absolute cognitive gains and that adverse events, including symptomatic ARIA, were more common on active drug and may even affect trial blinding [1] [3]. In practice, the decision to treat requires individualized risk assessment, genetic and medication review, and commitment to the MRI/lab monitoring protocols that trial data and major centers recommend [1] [13] [12].