Most Common Side Effects of Leqembi
Lecanemab (Lecanemab-irmb), sold as Leqembi, targets amyloid plaques in Alzheimer's disease. The most frequent side effects, affecting over 10% of patients in clinical trials, include infusion-related reactions (like headache, nausea, dizziness, fever, and fatigue) in 26% of users versus 7% on placebo, and amyloid-related imaging abnormalities (ARIA) with brain edema or effusions in 13% versus under 2% on placebo.[1][2]
What Is ARIA and How Common Is It?
ARIA involves brain swelling (ARIA-E) or bleeding (ARIA-H), detected mainly via MRI. In the phase 3 Clarity AD trial, ARIA-E occurred in 12.6% of Leqembi patients (mostly mild to moderate, asymptomatic), with 2.4% serious cases leading to hospitalization. ARIA-H affected 17%, often microhemorrhages. Risks rise with ApoE4 gene variants—up to 45% ARIA-E incidence in homozygous carriers—and higher doses.[1][3] Symptoms can include headache, confusion, seizures, or falls; monitoring with MRIs every 8 weeks (first 3 infusions) or 12 weeks thereafter is standard.[2]
Serious Risks and When They Occur
Severe hypersensitivity reactions happen during or within 4 hours of infusion in under 1% but require immediate stopping. Hypersensitivity affected 1.1%; anaphylaxis or angioedema is possible. Other serious issues: seizures (0.7%), superficial siderosis (iron deposits causing brain bleeding risk), and ischemic stroke (0.7%). Leqembi carries a boxed warning for ARIA risks, worsened by anticoagulants or antiplatelets.[1][2] Deaths linked to ARIA occurred in trials (3 on Leqembi vs. 0 placebo), though causality is unclear.[3]
Side Effects by Timing and Management
Most ARIA emerges early—median 91 days after first dose for edema, 77 days for effusions—with 70% resolving by trial end. Infusion reactions peak during or post-first doses (41% first infusion), dropping to 20% by third. Manage with slower infusions (starting at 45-60 minutes, up to 2 hours if needed), premeds like acetaminophen, or temporary pauses for moderate ARIA.[1][2] No routine premedication is required, but temporary discontinuation follows confirmed moderate/severe ARIA-E.[4]
Differences in Trial Populations and Real-World Data
Trial patients averaged 71 years old, mostly mild Alzheimer's. ApoE4 carriers (common in 15-25% of population) face 2-3x higher ARIA odds. Post-approval data (limited as of 2024) shows similar profiles, but expanded use may reveal more in diverse groups. Avoid in those with recent bleeds or unstable vascular disease.[1][3]
Comparisons to Similar Drugs Like Kisunla
Leqembi (10 mg/kg biweekly IV) has lower ARIA-E (13%) than monthly high-dose Kisunla (donanemab, 24-36%) at 24%, but both target amyloid. Leqembi slows decline 27% at 18 months versus 35% for Kisunla; side effect profiles overlap but Kisunla pauses more for ARIA.3
[1]: Leqembi Prescribing Information (FDA, 2023)
[2]: Clarity AD Trial (NEJM, 2023)
[3]: FDA Approval Summary (2023)
[4]: Leqembi HCP Guide (Eisai)