What are common side effects of monoclonal antibody Alzheimer treatments like lecanemab and aducanumab?

1. Why ARIA dominates safety conversations — the imaging abnormality that matters

Clinical evidence positions amyloid-related imaging abnormalities (ARIA) as the most prominent safety concern for anti-amyloid monoclonal antibodies. Trial and product-label documents for lecanemab list ARIA as a primary adverse event, noting that ARIA can be asymptomatic or present with neurological symptoms such as headache, confusion, or dizziness, and may include brain swelling (ARIA‑E) or microhemorrhages and superficial siderosis (ARIA‑H) ^{[1] [6]}. Phase 2 data for lecanemab showed ARIA‑E under 10% overall but markedly higher rates among APOE ε4 carriers and especially homozygotes, demonstrating a clear genetic risk modifier ^[2]. Aducanumab trials reported even higher ARIA incidences with some high‑dose arms, reaching rates upwards of a third to 40% in certain analyses, indicating that dose and patient selection substantially affect ARIA frequency ^{[7] [3]}.

2. Infusion reactions and common, non‑imaging side effects — what patients actually feel

Beyond imaging findings, clinical trials consistently report infusion-related reactions, headache, and allergic-type events as frequent, tangible side effects patients experience. Lecanemab trial data recorded infusion-related reactions in about one quarter of participants and headaches among common complaints, reflecting real‑world tolerability issues that clinicians must manage at administration ^{[4] [1]}. Product guidance for LEQEMBI explicitly lists infusion reactions and serious allergic reactions among potential risks and counsels monitoring during and after infusions ^[1]. Observational and safety‑surveillance reports emphasize that while many of these events are manageable with supportive care or temporary treatment interruption, they nonetheless contribute to treatment burden and inform shared decision‑making about initiating therapy, especially in older patients or those with comorbidities ^[8].

3. Serious bleeding, strokes, and the genetic vulnerability angle clinicians cannot ignore

Multiple sources document brain bleeding and stroke‑like events as less frequent but clinically serious risks tied to ARIA‑H and hemorrhagic complications. Aducanumab high‑dose trials reported substantial rates of brain swelling or bleeding, with some datasets showing over 40% incidence among certain high‑exposure groups; these findings propelled careful review of risk–benefit tradeoffs and highlighted the need for MRI monitoring protocols ^{[7] [3]}. Lecanemab and donanemab trial programs likewise recorded brain hemorrhage signals, with donanemab reporting up to ~30% ARIA in some cohorts, underlining that anti‑amyloid potency and exposure correlate with hemorrhagic risk ^[9]. APOE ε4 carriage repeatedly emerges as a predictor of higher ARIA risk, particularly for homozygotes, making genotyping a pivotal consideration when counseling patients ^{[2] [3]}.

4. Diverging numbers and interpretations — why different studies give different risks

Reported ARIA and adverse‑event frequencies vary widely across publications and product documents because of differences in dose levels, trial populations, imaging schedules, and safety definitions. Phase 2 lecanemab trials reported lower ARIA‑E rates (<10%) compared with pooled or high‑dose aducanumab analyses that found 35–40% ARIA rates; differences stem from trial design, participant APOE status distribution, and escalation to higher exposures in some aducanumab arms ^{[2] [3] [7]}. Real‑world surveillance and long‑term pharmacovigilance data emphasize that clinical‑trial populations are more selected and follow shorter durations, so real‑world incidence, rare events, and longer‑term consequences may differ; regulators and investigators therefore call for ongoing monitoring to reconcile trial estimates with post‑approval experience ^{[8] [5]}.

5. Emerging and rare signals — why vigilance must continue beyond ARIA

Post‑marketing and pharmacovigilance analyses raise signals beyond ARIA that merit continued scrutiny. Long‑term surveillance flagged disproportionate reporting signals, including rare but serious events that were not prominent in randomized trials, underscoring limitations of trial size and duration for detecting uncommon harms ^[5]. Safety documents for lecanemab and programmatic reviews recommend periodic MRI monitoring, especially early during treatment, and highlight the need for pharmacovigilance frameworks to detect delayed or rare outcomes. These observations imply that benefit–risk calculus may shift as longer exposures and broader populations are treated, making transparent data collection and reporting essential ^{[1] [8]}.

6. Putting the evidence into clinical perspective — balancing promise and precaution

The clinical picture is one of modest cognitive benefit for some patients paired with clear and measurable safety risks, led by ARIA and infusion‑related events, amplified in APOE ε4 carriers and at higher drug exposures. Regulatory labels, trial publications, and surveillance reports converge on the need for MRI monitoring, genetic consideration, and patient counseling about infusion logistics and bleeding risks ^{[6] [1] [3]}. Stakeholders differ in emphasis—some stress potential disease‑modifying effects, others caution over safety and uncertain long‑term impact—so decisions must be individualized, documented, and accompanied by structured monitoring and reporting to capture emergent safety signals ^{[9] [8]}.