What were the ARIA rates and severity for lecanemab versus aducanumab in pivotal trials?

1. What the pivotal lecanemab data actually showed — lower ARIA numbers, mostly mild and transient

In the lecanemab pivotal program, clinical trial reports and updates show ARIA‑E in roughly 9.9–13.6% of treated participants and ARIA‑H in the mid‑teens, with most ARIA events classified as mild or moderate and often asymptomatic. Trial investigators reported clustering of ARIA events in the early months of treatment and spontaneous radiographic resolution over weeks to months, and a stronger incidence among APOE ε4 carriers, especially homozygotes ^{[1] [5] [2]}. Post‑approval and real‑world series found similar or slightly higher pooled ARIA frequencies when broader populations were treated but noted that many programs excluded APOE ε4 homozygotes, potentially lowering observed real‑world rates compared with unrestricted trial enrollment ^{[6] [2]}. The lecanemab safety narrative emphasizes monitoring, early imaging surveillance, and that most ARIA did not result in long‑term sequelae ^{[1] [2]}.

2. Aducanumab’s pivotal trials — much higher ARIA incidence and a different clinical profile

Aducanumab’s EMERGE and ENGAGE trials reported overall ARIA incidences in the 36–41% range, with ARIA‑E observed in roughly 35% and symptomatic or clinically consequential cases reported at higher rates than in lecanemab trials. Pooled analyses of the aducanumab registrational data documented a substantial proportion of participants with radiographic ARIA and a nontrivial subset experiencing symptoms such as headache or confusion; rare serious events, including hospitalizations, were reported ^{[3] [4]}. Investigators linked elevated ARIA risk to APOE ε4 carriage and higher doses, and regulators and trialists highlighted the need for intensive MRI monitoring in the aducanumab programs. The aducanumab dataset therefore carries a markedly different safety signal compared with lecanemab’s pivotal reports ^{[3] [4]}.

3. Why numbers aren’t a clean apples‑to‑apples comparison — design, doses, and patient mix matter

Direct comparisons between lecanemab and aducanumab are limited because trial designs, dosing regimens, imaging schedules, inclusion/exclusion criteria, and APOE ε4 distributions differed across studies. Lecanemab’s core and extension studies used a specified biweekly 10 mg/kg regimen with predefined MRI monitoring windows; aducanumab trials pooled multiple dose cohorts and had variable exposure across participants, influencing ARIA detection. Observational studies and meta‑analyses stress that APOE ε4 homozygosity, concomitant antithrombotic use, prior microhemorrhages, and age substantially modify ARIA risk, so population composition can shift apparent ARIA rates up or down ^{[7] [8] [5]}. These methodological differences mean numerical differences reflect both drug properties and the contexts in which they were measured ^{[7] [8]}.

4. Severity and outcomes — most ARIA are manageable but serious cases occur

Across the datasets, the majority of ARIA events for both agents were radiologic and asymptomatic or mildly symptomatic, resolving with temporary dose interruption or discontinuation and supportive care. Lecanemab reports emphasize low rates of persistent neurologic damage and few severe events, while aducanumab datasets contained a higher absolute number of symptomatic and more severe ARIA episodes, including some hospitalizations and more frequent microhemorrhages ^{[2] [1] [4]}. Meta‑analyses quantify symptomatic ARIA and severe ARIA as minority outcomes but caution that even low frequencies translate to important clinical considerations when treating large numbers of older patients on antithrombotics ^{[8] [2]}.

5. How different stakeholders interpret these findings — efficacy tradeoffs, regulatory posture, and clinical guidance

Pharmaceutical sponsors and some clinical investigators emphasize efficacy‑safety balances and individualized risk stratification, arguing that ARIA is an expected, monitorable effect of amyloid clearance. Regulators and health systems have responded variably: aducanumab’s more prominent ARIA signal contributed to intense debate around approval and post‑market controls, while lecanemab’s lower reported ARIA rates influenced a distinct rollout with MRI protocols and APOE‑guided counseling. Independent reviews call for transparent reporting, head‑to‑head trials, and systematic post‑marketing surveillance to settle residual uncertainty about comparative safety ^{[9] [6] [8]}.