What is the latest (since 2022) evidence and literature regarding use of lecanemab?

Comment by InpharmD Researcher

Since 2022, the literature on lecanemab has expanded, anchored by its 2023 U.S. Food and Drug Administration (FDA) approval based on the phase 3 CLARITY AD trial (Table 1), which demonstrated reduced amyloid burden and less decline in cognitive and functional measures over 18 months compared with placebo. Subsequent guidance and newer literature emphasize use in carefully selected patients with early Alzheimer’s disease and confirmed amyloid pathology, with treatment protocols closely aligned with trial populations and routine magnetic resonance imaging monitoring due to risks such as amyloid-related imaging abnormalities. Additional post hoc and longer-term extension data suggest continued effects on biomarkers, cognition, function, and patient-reported outcomes over time, while indicating that benefits are modest and directed toward slowing progression. Emerging real-world and pharmacovigilance data also suggest that lecanemab is feasible to implement in clinical practice, while consistently identifying amyloid-related imaging abnormalities and infusion-related reactions as key safety concerns requiring structured monitoring and patient selection.

Background

In 2023, a U.S. Food and Drug Administration (FDA) press announcement stated that lecanemab (Leqembi) was granted traditional approval for the treatment of Alzheimer’s disease (AD) after conversion from accelerated approval following confirmation of clinical benefit in the phase 3 CLARITY AD trial (Table 1). The FDA advisory committee unanimously agreed that the trial verified clinical benefit for the indicated use, and lecanemab became the first amyloid beta-directed antibody to receive traditional approval for Alzheimer’s disease. [1]

The 2023 Alzheimer’s Disease and Related Disorders Therapeutics Work Group (ADRD TWG) developed lecanemab Appropriate Use Recommendations (AUR) based on the FDA-approved prescribing information, phase 2 and phase 3 trial data, and expert opinion to guide real-world clinical practice. Lecanemab is recommended only for patients with mild cognitive impairment (MCI) due to AD or mild AD dementia (Mini-Mental State Examination [MMSE] 22 to 30) with confirmed amyloid pathology by positron emission tomography (PET) or cerebrospinal fluid (CSF), with recommendations adhering closely to CLARITY AD trial inclusion and exclusion criteria. Apolipoprotein E (APOE) genotyping is recommended for all candidates, as APOE4 carriers, especially homozygotes, are at higher risk for amyloid-related imaging abnormalities (ARIA). Patients receiving anticoagulants should not receive lecanemab, and thrombolytics should not be administered to lecanemab recipients; aspirin and standard antiplatelet agents may be considered. Lecanemab is given at 10 mg/kg intravenously (IV) every 2 weeks without titration, with magnetic resonance imaging (MRI) monitoring at baseline and before the 5th, 7th, and 14th infusions, plus an additional week 52 MRI for APOE4 carriers or those with prior ARIA. Mild asymptomatic ARIA may allow continued dosing with close monitoring, whereas moderate or severe radiographic ARIA or symptomatic ARIA should prompt suspension; discontinuation is recommended for severe ARIA, macrohemorrhage, superficial siderosis, more than 10 new microhemorrhages, more than 2 ARIA episodes, or need for anticoagulation. Infusion reactions are typically mild to moderate and managed with diphenhydramine and acetaminophen, with premedication recommended before subsequent infusions in patients who experience an infusion reaction. Finally, the AUR emphasizes thorough, culturally sensitive communication with patients and care partners regarding realistic treatment goals (slowing disease progression rather than improving cognition), monitoring requirements, and ARIA risks as a cornerstone of good clinical practice, and recommends enrolling all treated patients in the Alzheimer's Network for Treatment and Diagnostics (ALZ-NET) registry or equivalent. [2]

A 2024 retrospective observational study evaluated 71 patients at a regional medical center to describe real-world implementation of lecanemab and identify lessons learned from early treatment experience (Table 3). Upon completion of the study, the authors found that successful program implementation required multidisciplinary planning, weekly case review, nurse navigator oversight, standardized radiology reporting, and emergency department protocols emphasizing MRI rather than computed tomography for suspected ARIA. Clinically, the authors reported that implementation of a pretreatment cocktail of acetaminophen, loratadine, and famotidine reduced infusion-related adverse events from 45% to 26%, and emphasized the importance of specialist review of baseline MRI, repeat cognitive testing when scores are discrepant, and use of consistent 3.0T MRI imaging for ARIA surveillance. Additional practical considerations included transportation/caregiver requirements, infusion-center capacity limitations, and patient treatment refusal related to travel burden, time commitment, adverse event concerns, and cost. From a reimbursement perspective, the authors noted that insurance approval and payment processes were a major barrier, frequently requiring appeals, peer-to-peer review, additional documentation, and occasionally manufacturer patient assistance programs, resulting in treatment delays despite eventual access. Overall, lecanemab was generally well tolerated in patients with MCI and mild AD dementia, and identification of workflow and management improvements enhanced the infusion experience. [3]

A 2025 pharmacovigilance disproportionality study evaluated adverse event reports associated with lecanemab in the FDA Adverse Event Reporting System (FAERS) from January 2023 through June 2024. Among 1,307,937 FAERS reports, 1,679 adverse events were identified with lecanemab. The strongest safety signals were observed for ARIA, including ARIA with microhemorrhages (reporting odds ratio [ROR] 11,221.5; 95% CI 5,706.2 to 22,067.5) and ARIA with edema/effusion (ROR 8927.3; 95% CI 5,243.6 to 15,199.1). Other notable reported adverse events included infusion-related reactions (ROR 24.9; 95% CI 18.9 to 32.8), headache (ROR 10.2; 95% CI 8.6 to 12.2), and confusional states (ROR 15.0; 95% CI 11.4 to 19.7). The authors concluded these findings support vigilant monitoring for ARIA and neurologic/psychiatric adverse events during lecanemab treatment. [4]

References: [1] U.S. Food and Drug Administration (FDA). FDA Converts Novel Alzheimer’s Disease Treatment to Traditional Approval. Updated July 6, 2023. Accessed April 8, 2026. https://www.fda.gov/news-events/press-announcements/fda-converts-novel-alzheimers-disease-treatment-traditional-approval
[2] Cummings J, Apostolova L, Rabinovici GD, et al. Lecanemab: Appropriate Use Recommendations. J Prev Alzheimers Dis. 2023;10(3):362-377. doi:10.14283/jpad.2023.30
[3] Shields LBE, Hust H, Cooley SD, et al. Initial Experience with Lecanemab and Lessons Learned in 71 Patients in a Regional Medical Center. J Prev Alzheimers Dis. 2024;11(6):1549-1562. doi:10.14283/jpad.2024.159
[4] Han J, Fang Y, Campbell N. Real-world safety profile of lecanemab: A disproportionality analysis of adverse events in the FDA adverse event reporting system. JAPhA Pharmacotherapy. 2025;2(2):100015. doi:https://doi.org/10.1016/j.japhar.2025.100015
Literature Review

A search of the published medical literature revealed 11 studies investigating the researchable question:

What is the latest (since 2022) evidence and literature regarding use of lecanemab?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→


Please see Tables 1-11 for your response.

 

Lecanemab in Early Alzheimer’s Disease

Design

Multicenter, double-blind, placebo-controlled, parallel-group, phase 3 trial (Study 301 CLARITY AD)

N= 1,795

Objective

To determine the safety and efficacy of lecanemab in participants with early Alzheimer’s disease (AD)

Study Groups

Lecanemab 10 mg/kg biweekly (n= 898)

Placebo (n= 897) 

Inclusion Criteria

Aged 50 to 90 years with either mild cognitive impairment due to Alzheimer’s disease or mild Alzheimer’s disease–related dementia on the basis of National Institute on Aging–Alzheimer’s Association criteria, amyloid positivity determined by positron emission tomography (PET) or cerebrospinal fluid (CSF) measurement of amyloid-β (Aβ), objective impairment in episodic memory as indicated by at least 1 standard deviation below the age-adjusted mean in the Wechsler Memory Scale IV–Logical Memory II

Exclusion Criteria

Females who were breastfeeding or pregnant; females of childbearing potential meeting certain criteria; neurological condition contributing to cognitive impairment above and beyond that caused by subject's AD; history of transient ischemic attacks, stroke, or seizures within 12 months of screening; psychiatric diagnosis or symptoms that could interfere with study procedures; Geriatric Depression Scale (GDS) score ≥ 8; contraindications to magnetic resonance imaging (MRI); evidence of other clinically significant lesions on brain MRI that could indicate a dementia diagnosis other than AD

Methods

Eligible participants were randomized (1:1) to receive intravenous lecanemab 10 mg/kg every 2 weeks or placebo. Randomization was stratified according to clinical subgroup (mild cognitive impairment due to Alzheimer’s disease or mild Alzheimer’s disease–related dementia), the presence or absence of concomitant approved medication for symptoms of Alzheimer’s disease at baseline (e.g., acetylcholinesterase inhibitors, memantine, or both), apolipoprotein E (ApoE) ε4 carriers or noncarriers, and geographic region.

Participants underwent serial blood testing for plasma biomarkers and could participate in three optional substudies that evaluated longitudinal changes in brain amyloid burden as measured by PET, brain tau pathologic features as measured by PET, and CSF biomarkers of AD. An independent medical monitoring team, whose members were unaware of the trial-group assignments, reviewed amyloid-related imaging abnormalities-edema (ARIA), infusion-related reactions, and hypersensitivity reactions.

Efficacy analyses were performed in the modified intention-to-treat population, which was defined as the group of randomly assigned participants who received at least one dose of lecanemab or placebo and who had a baseline assessment and at least one postdose primary efficacy measurement.

Duration

March 2019 through March 2021

Intervention: 18 months

Outcome Measures

Primary: change from baseline to 18 months in score on Clinical Dementia Rating–Sum of Boxes (CDR-SB)

Secondary: change from baseline to 18 months in amyloid burden on PET as measured in centiloids, score on 14-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog14), Alzheimer’s Disease Composite Score (ADCOMS), score on Alzheimer’s Disease Cooperative Study–Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL)

Baseline Characteristics

  

Lecanemab (n= 859)

Placebo (n= 875)

Age, years

 71.4 ± 7.9 71.0 ± 7.8

Female

 443 (51.6%) 464 (53.0%)

Race

White

Black

Asian

Other or Missing

 

655 (76.3%)

20 (2.3%)

147 (17.1%)

37 (4.3%)

 

677 (77.4%)

24 (2.7%)

148 (16.9%)

26 (3.0%)

Hispanic ethnic group

 107 (12.5%) 108 (12.3%)

Time since diagnosis, years

 1.41 ± 1.51 1.34 ± 1.54

Time since onset of symptoms, years

 4.13 ± 2.35 4.15 ± 2.53

Global CDR score

0.5

1.0

 

694 (80.8%)

165 (19.2%)

 

709 (80.7%)

169 (19.3%)

Clinical subgroup

Mild dementia due to AD

Mild cognitive impairment due to AD

 

331 (38.5%)

528 (61.5%)

 

331 (37.8%)

544 (62.2%)

ApoE ε4 status

Noncarrier

Carrier

Heterozygotes

Homozygotes

 

267 (31.1%)

592 (68.9%)

456 (53.1%)

136 (15.8%)

 

275 (31.4%)

600 (68.6%)

468 (53.5%)

132 (15.1%

Current use of medication for symptoms of AD

 447 (52%) 468 (53.5%)

CDR-SB score

Mean

Range

 

3.17 ± 1.34

0.5 to 8.0

 

3.22 ± 1.34

0.5 to 8.5

Amyloid burden on PET, centiloids

Mean

Range

 

77.92 ± 44.84

-16.6 to 213.2

 

75.03 ± 41.82

-17.0 to 179.6

ADAS-cog14 score

Mean

Range

 

24.45 ± 7.08

4.7 to 47.7

 

24.37 ± 7.56

5.0 to 60.7

ADCOMS

Mean

Range

 

0.398 ± 0.147

0.08 to 0.94

 

0.400 ± 0.147

0.07 to 0.91

ADCS-MCI-ADL score

Mean

Range

 

41.2 ± 6.6

13 to 53

 

40.0 ± 6.9

12 to 53

Mini-Mental Status Examination (MMSE) score

Mean

Range

 

25.5 ± 2.2

22 to 30

 

25.6 ± 2.2

22 to 30

Results

Endpoint

Lecanemab (n= 859)

Placebo (n= 875)

Change from baseline to 18 mo in CDR-SB score

No. of participants evaluated

Adjusted mean change

Adjusted mean difference vs. placebo (95% confidence interval [CI])

p-value vs. placebo

 

859

1.21

-0.45 (-0.67 to -0.23)

< 0.001

 

875

1.66

-

-

Change from baseline to 18 mo in amyloid burden on PET

No. of participants evaluated

Adjusted mean change, centiloids

Adjusted mean difference vs. placebo (95% CI), centiloids

p-value vs. placebo

 

354

-55.48

-59.12 (-62.64 to -55.60)

< 0.001

 

344

3.64

-

-

Change from baseline to 18 mo in ADAS-cog14 score

No. of participants evaluated

Adjusted mean change

Adjusted mean difference vs. placebo (95% CI)

p-value vs. placebo

 

854

4.14

-1.44 (-2.27 to -0.61)

< 0.001

 

872

5.58

-

-

Change from baseline to 18 mo in ADCOMS

No. of participants evaluated

Adjusted mean change

Adjusted mean difference vs. placebo (95% CI)

p-value vs. placebo

 

857

0.164

-0.050 (-0.074 to -0.027)

< 0.001

 

875

0.214

-

-

Change from baseline to 18 mo in ADCS-MCI-ADL score

No. of participants evaluated

Adjusted mean change

Adjusted mean difference vs. placebo (95% CI)

p-value vs. placebo

 

783

-3.5

2.0 (1.2 to 2.8)

< 0.001

 

796

-5.5

-

-

Modified Intention-to-Treat Analysis

Adverse Events

Common Adverse Events: The most common adverse events (affecting >10% of the participants) in the lecanemab group were infusion-related reactions (26.4% with lecanemab vs. 7.4% with placebo); ARIA with cerebral microhemorrhages, cerebral macrohemorrhages, or superficial siderosis (ARIA-H; 17.3% vs. 9.0%); amyloid-related imaging abnormalities-edema (ARIA-E; 12.6% vs. 1.7%); headache (11.1% vs. 8.1%); and falls (10.4% and 9.6%). 

Serious Adverse Events: The most commonly reported serious adverse events were infusion-related reactions (1.2% in the lecanemab group vs. 0 in the placebo group), ARIA-E (0.8% vs. 0), atrial fibrillation (0.7% vs. 0.3%), syncope (0.7% vs. 0.1%), and angina pectoris (0.7% vs. 0).

Percentage that Discontinued due to Adverse Events: 6.9% in the lecanemab group vs. 2.9% in the placebo group

Study Author Conclusions

Lecanemab reduced markers of amyloid in early Alzheimer’s disease and resulted in moderately less decline on measures of cognition and function than placebo at 18 months but was associated with adverse events. Longer trials are warranted to determine the efficacy and safety of lecanemab in early Alzheimer’s disease.

InpharmD Researcher Critique

The primary outcome of this analysis, change in CDR-SB score, is not meant as an assessment of disease progression; CDR-SB is a tool for diagnosis. However, the consistent reductions in additional tools/questionnaires allows the hypothesis (not conclusion) that lecanemab may be able to slow disease progression.

This study includes a large sample of ApoE4 genotype carriers who make up approximately 69% of participants. Such individuals were removed from prior large trials due to a higher risk of ARIA-E than non-ApoE4 carriers; therefore, these are the first major trial results showing a largely unskewed safety profile for lecanemab versus placebo.

The dropout rate in this study was relatively high (17.2%), but a sensitivity analysis that evaluated the effect of missed doses was consistent with the primary outcome analysis. Additionally, the modified intention-to-treat analysis did not impute missing values, but again, a sensitivity analysis with the standard intention-to-treat population with imputation observed similar results.

 

References:
[1] van Dyck CH, Swanson CJ, Aisen P, et al. Lecanemab in Early Alzheimer's Disease. N Engl J Med. 2023;388(1):9-21. doi:10.1056/NEJMoa2212948

 

Lecanemab Clarity AD: Quality-of-Life Results from a Randomized, Double-Blind Phase 3 Trial in Early Alzheimer’s Disease

Design

Post-hoc analysis of CLARITY AD, a multicenter, double-blind, placebo-controlled, parallel-group, phase 3 trial

N= 1,795

Objective

To describe the health-related quality-of-life (HRQoL) results from Clarity AD

Study Groups

Lecanemab 10 mg/kg biweekly (n= 898)

Placebo (n= 897) 

Inclusion Criteria

Aged 50 to 90 years with either mild cognitive impairment due to Alzheimer’s disease or mild Alzheimer’s disease-related dementia on the basis of National Institute on Aging–Alzheimer’s Association criteria, amyloid positivity determined by positron emission tomography (PET) or cerebrospinal fluid (CSF) measurement of amyloid-β (Aβ), objective impairment in episodic memory as indicated by at least 1 standard deviation below the age-adjusted mean in the Wechsler Memory Scale IV–Logical Memory II

Exclusion Criteria

Females who were breastfeeding or pregnant; females of childbearing potential meeting certain criteria; neurological condition contributing to cognitive impairment above and beyond that caused by subject's AD; history of transient ischemic attacks, stroke, or seizures within 12 months of screening; psychiatric diagnosis or symptoms that could interfere with study procedures; Geriatric Depression Scale (GDS) score ≥ 8; contraindications to magnetic resonance imaging (MRI); evidence of other clinically significant lesions on brain MRI that could indicate a dementia diagnosis other than AD

Methods

Eligible participants were randomized (1:1) to receive intravenous lecanemab 10 mg/kg every 2 weeks or placebo. Randomization was stratified according to clinical subgroup (mild cognitive impairment due to Alzheimer’s disease or mild Alzheimer’s disease-related dementia), the presence or absence of concomitant approved medication for symptoms of Alzheimer’s disease at baseline (e.g., acetylcholinesterase inhibitors, memantine, or both), apolipoprotein E (ApoE) ε4 carriers or noncarriers, and geographic region.

Participants underwent serial blood testing for plasma biomarkers and could participate in three optional substudies that evaluated longitudinal changes in brain amyloid burden as measured by PET, brain tau pathologic features as measured by PET, and CSF biomarkers of AD. An independent medical monitoring team, whose members were unaware of the trial-group assignments, reviewed amyloid-related imaging abnormalities-edema (ARIA), infusion-related reactions, and hypersensitivity reactions.

Health-Related Quality of Life Assessments included the European QOL-5 Dimensions (EQ-5D-5L), Quality of Life in Alzheimer's Disease (QOL-AD), and Zarit Burden Interview (ZBI) scales. Each tool was given at baseline and every 6 months thereafter; the EQ-5D-5L is only given to the patient, the ZBI is only given to the caregiver, and the QOL-AD is given to both.

Duration

March 2019 through March 2021

Intervention: 18 months

Outcome Measures

Primary: change from baseline to 18 months in score on Clinical Dementia Rating–Sum of Boxes (CDR-SB)

Secondary: change from baseline to 18 months in amyloid burden on PET as measured in centiloids, score on 14-item cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog14), Alzheimer’s Disease Composite Score (ADCOMS), score on Alzheimer’s Disease Cooperative Study–Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL)

Exploratory: HRQoL after 18 months

Baseline Characteristics

  

Lecanemab (n= 859)

Placebo (n= 875)

Age, years

 71.4 ± 7.9 71.0 ± 7.8

Female

 443 (51.6%) 464 (53.0%)

Race

White

Black

Asian

Other or Missing

 

655 (76.3%)

20 (2.3%)

147 (17.1%)

37 (4.3%)

 

677 (77.4%)

24 (2.7%)

148 (16.9%)

26 (3.0%)

Hispanic ethnic group

 107 (12.5%) 108 (12.3%)

ApoE ε4 status

Noncarrier

Carrier

Heterozygotes

Homozygotes

 

267 (31.1%)

592 (68.9%)

456 (53.1%)

136 (15.8%)

 

275 (31.4%)

600 (68.6%)

468 (53.5%)

132 (15.1%)

Baseline HRQoL scores

EQ-5D-5L – Health Today (Subject)

QOL-AD – Total Score (Subject)

QOL-AD – Total Score (Subject by Proxy)

ZBI – Total Score (Care Partner)

 

82.2 ± 13.9

39.0 ± 6.2

37.1 ± 6.0

17.2 ± 12.2

 

81.4 ± 14.2

39.1 ± 6.1

36.6 ± 6.0

17.6 ± 11.8

Caregivers

Spouse/partner

Child/grandchild

Friends or others

Other relatives

 

70.0%

20.1%

6.7%

3.3%

 

70.9%

17.7%

7.4%

3.9%

Caregiver lived with the study participant

76.8%

 77.0%

Caregiver hours/week spent with study participant

85.0 ± 58.8

80.9 ± 55.8

Results

After 18 months, there was 49.1% less decline in the EQ-5D-5L scores with lecanemab compared to placebo (p= 0.00383). A separation in the scores could be seen after 6 months, but the results did not become significant until month 18. The anxiety/depression and usual activity subscores significantly favored lecanemab, while mobility, pain/discomfort, and self-care subscores were not significantly different. The mean adjusted treatment difference between the overall scores was 2.017.

For the subject-directed QOL-AD scores, there was 55.6% less decline with lecanemab compared to placebo (p= 0.00231). Like the EQ-5D-5L scores, there was no significant difference until month 18. The mean adjusted treatment difference between the scores was 0.657.

The caregiver QOL-AD scores showed 22.9% less decline (p= 0.02558) with lecanemab. Unlike the patients' scores, significant differences were noted at 12 months. The mean adjusted treatment difference between the scores was 0.535.

For the ZBI study partner total score, there was a highly statistically significant difference between placebo and lecanemab on change from baseline, with a 38.4% less progression (p= 0.00002). Significant differences were noted after 6 months. The mean adjusted treatment difference between the overall scores was -2.211.

Adverse Events

Common Adverse Events: The most common adverse events (affecting >10% of the participants) in the lecanemab group were infusion-related reactions (26.4% with lecanemab vs. 7.4% with placebo); ARIA with cerebral microhemorrhages, cerebral macrohemorrhages, or superficial siderosis (ARIA-H; 17.3% vs. 9.0%); amyloid-related imaging abnormalities-edema (ARIA-E; 12.6% vs. 1.7%); headache (11.1% vs. 8.1%); and falls (10.4% and 9.6%). 

Serious Adverse Events: The most commonly reported serious adverse events were infusion-related reactions (1.2% in the lecanemab group vs. 0 in the placebo group), ARIA-E (0.8% vs. 0), atrial fibrillation (0.7% vs. 0.3%), syncope (0.7% vs. 0.1%), and angina pectoris (0.7% vs. 0).

Percentage that Discontinued due to Adverse Events: 6.9% in the lecanemab group vs. 2.9% in the placebo group

Study Author Conclusions

Lecanemab was associated with a relative preservation of HRQoL and less increase in caregiver burden, with consistent benefits seen across different quality of life scales and within scale subdomains.

InpharmD Researcher Critique

 The HRQoL tools used were validated and appropriate. However, the magnitude of change in scores was not completely reported for each interval. While there were significant differences in the comparative change from baseline (given as percentages), the mean total score difference may not be clinically meaningful for the EQ-5D-5L and QOL-AD scores.

 

References:
[1] [1] Cohen S, van Dyck CH, Gee M, et al. Lecanemab Clarity AD: Quality-of-Life Results from a Randomized, Double-Blind Phase 3 Trial in Early Alzheimer's Disease. J Prev Alzheimers Dis. 2023;10(4):771-777. doi:10.14283/jpad.2023.123

Initial Experience with Lecanemab and Lessons Learned in 71 Patients in a Regional Medical Center
Design

Retrospective observational study

N= 71
Objective

To describe the early experience and lessons learned with lecanemab in a regional community medical center
Study Groups

All patients (N= 71)
Inclusion Criteria

Patients with mild cognitive impairment or mild dementia due to Alzheimer's disease and amyloid positivity of cerebrospinal fluid (CSF) Alzheimer’s disease (AD) biomarkers or by amyloid PET scan
Exclusion Criteria

Severe vascular dementia, more than 4 microhemorrhages, history of active cancer, severe psychiatric disorders, currently pregnant, poorly controlled immunologic disorders, unstable medical conditions, recent stroke or seizures, cerebral amyloid angiopathy-related inflammation, currently receiving aducanumab, and certain anticoagulant therapies
Methods

Patients received intravenous lecanemab 10 mg/kg per infusion every 2 weeks. Baseline brain MRIs were performed prior to the initial lecanemab administration, and surveillance MRIs were obtained before the 5th, 7th, and 14th infusions. If ARIA was detected, monthly MRIs were required until resolution. A multidisciplinary team managed the treatment process.
Duration

August 25, 2023 to March 1, 2024
Outcome Measures

Early experience and lessons learned with lecanemab, incidence of amyloid-related imaging abnormalities (ARIA), infusion-related side effects
Baseline Characteristics  

All patients (N= 71)

Age at 1st lecanemab infusion, years (range)

 72 (49-90)

Female

 44 (62%)

White

 68 (96%)
Body Mass Index, kg/m2 (range)

27.0 (17.8-45.0)

Hypertension

 34 (48%)

Hypercholesterolemia

 51 (72%)

Diabetes mellitus

 17 (24%)

Cardiovascular disease (other than hypertension)

 22 (31%)

ApoE genotype - E4 heterozygous

 36 (51%)

ApoE genotype - E4 homozygous

 9 (13%)

Diagnosis - Mild dementia

 36 (50.7%)

Diagnosis - MCI

 35 (49.3%)

Abbreviations: MCI, mild cognitive impairment.
Results  

All patients (N= 71)

Infusion-related adverse effects after 1st lecanemab infusion

 26 (37%)

ARIA-H/ARIA-E detected on surveillance brain MRI (n= 50)

 12 (24%)

Infusion-related adverse effects after 2nd lecanemab infusion (n= 67)

 5 (7%)

Abbreviations: ARIA-E, amyloid-related imaging abnormality-edema; ARIA-H, amyloid-related imaging abnormality-hemorrhage.

Among 50 patients who completed at least 1 surveillance magnetic resonance imaging study, amyloid-related imaging abnormalities (ARIA) were detected in 12 patients (24%), including isolated amyloid-related imaging abnormality-hemorrhage in 5, isolated amyloid-related imaging abnormality-edema in 3, and both in 4; 9 of 12 cases were asymptomatic.

ARIA occurred in 44% of ApoE E4 homozygotes and 17% of heterozygotes, and 7 patients required temporary or permanent suspension of lecanemab due to persistent ARIA, numerous lesions, or symptoms.
Adverse Events

Infusion-related adverse effects occurred in 37% of patients after the first infusion, most commonly headache and shaking/chills/rigors, decreasing to 7% after the second infusion and 4% to 6% during infusions 3 through 7, with no reported events after infusions 8 through 14. Two patients were evaluated in the emergency department after the first infusion, and 2 patients experienced serious behavioral reactions after diphenhydramine administration for infusion-related symptoms, prompting revision of the pretreatment protocol. One death occurred following the first infusion in a 75-year-old ApoE E4 homozygous patient who developed cardiorespiratory arrest shortly after treatment; the treating center considered the death most likely cardiac-related, although an association with lecanemab could not be excluded.
Study Author Conclusions

In conclusion, lecanemab was well-tolerated by most patients with MCI and mild dementia due to AD. By identifying numerous areas of improvement and implementing solutions, the lecanemab infusion experience for patients was enhanced. Providers treating patients with amyloid-lowering antibody medications should select patients most likely to benefit with a clearly positive risk-benefit profile.
Critique

The study provides valuable real-world insights into the use of lecanemab in a community setting, highlighting practical challenges and solutions. However, the modest sample size, short follow-up duration, and low diversity limit the generalizability of the findings. The retrospective design may also introduce bias.
References:
[1] [1] Shields LBE, Hust H, Cooley SD, et al. Initial Experience with Lecanemab and Lessons Learned in 71 Patients in a Regional Medical Center. J Prev Alzheimers Dis. 2024;11(6):1549-1562. doi:10.14283/jpad.2024.159
Lecanemab over a two-year duration: Key insights from a regional specialty medical center
Design

Retrospective and observational study

N= 187
Objective To evaluate the incidence of amyloid-related imaging abnormalities (ARIA) and other adverse events associated with lecanemab
Study Groups

Mild cognitive impairment (MCI; n= 109)

Mild dementia (n= 78)
Inclusion Criteria Patients treated with at least one lecanemab infusion at the Norton Neuroscience Institute Memory Center over a two-year duration

Exclusion Criteria

As reported in the authors' previous 6-month experience (Table 3): severe vascular dementia, more than 4 microhemorrhages, history of active cancer, severe psychiatric disorders, currently pregnant, poorly controlled immunologic disorders, unstable medical conditions, recent stroke or seizures, cerebral amyloid angiopathy-related inflammation, currently receiving aducanumab, and certain anticoagulant therapies
Methods Building on the authors’ previously published 6-month institutional experience, this expanded follow-up analysis evaluated patients receiving intravenous lecanemab 10 mg/kg every 2 weeks, with surveillance magnetic resonance imaging performed before the 5th, 7th, and 14th infusions. Beginning December 31, 2023, after early infusion-related adverse effects were observed during the initial 6-month experience, patients were pretreated prior to infusion with oral acetaminophen 650 mg, loratadine 10 mg, and famotidine 20 mg.
Duration

August 25, 2023 to August 24, 2025
Outcome Measures Incidence of ARIA, infusion-related adverse effects, discontinuation rates, Mini-Mental State Examination (MMSE) score changes
Baseline Characteristics   All patients (N= 187)

Diagnosis 

MCI

Mild dementia

 

109 (58.3%)

78 (41.7%)
Age at 1st lecanemab infusion, years (range) 73 (49-90)

Female

 127 (67.9%)

White

 181 (96.8%)
Body Mass Index, kg/m2 (range) 26.0 (17.6-45.0)

Comorbidities

Dyslipidemia

Hypertension

Cardiovascular disease (other than hypertension)

Diabetes mellitus

 

141 (75.4%)

86 (46.0 %)

60 (32.1 %)

35 (18.7 %)

Apolipoprotein E ε4 status

ε4 Heterozygote

ε4 Homozygote

 

102 (54.5%)

27 (14.4%)

Abbreviations: MCI, mild cognitive impairment
Results   All patients (N= 187)

Underwent at least one surveillance brain MRI scan following lecanemab initiation (n= 175)

ARIA detected

Both ARIA-H (with microhemorrhages) and ARIA-E (edema)

Solitary ARIA-H

Solitary ARIA-E

 

39 (22.3%)

13 (33.3%)

17 (43.6%)

9 (23.1 %)

ARIA-H/ARIA-E first detected on surveillance brain MRI (n= 39)

Before 5th infusion

Before 7th infusion

Before 14th infusion

 

29 (74.4 %)

7 (17.9 %)

3 (7.7 %)

Infusion-related adverse effects

 60 (32.1%)

Discontinued lecanemab after two year mark

Total

Due to cognitive decline/delusions/agitation

Due to ARIA progression

 

32 (17.1%)

10 (31.2 %)

9 (28.1 %)

Comparison of MMSE scores at baseline and after 1 year post-lecanemab (n= 73)

MMSE score increased

MMSE score decreased

 

13 (17.8%)

51 (69.9%)

Among 187 patients treated with lecanemab, 39 of 175 patients (22.3%) with at least 1 surveillance magnetic resonance imaging had evidence of ARIA, with 5 cases (12.8%) being symptomatic. ARIA occurred more frequently in Apolipoprotein E ε4 homozygotes, with 48.0% developing ARIA compared with 21.0% of heterozygotes and 12.7% of non-carriers, and was most commonly detected before the 5th infusion (74.4%).

Patients with greater baseline microbleed burden more frequently developed ARIA, while baseline MMSE score and diagnosis were not significant predictors of symptomatic ARIA.
Adverse Events

Infusion-related adverse effects occurred in 32.1% of patients, most commonly mild transient headache, with 90.0% occurring after the first infusion; incidence decreased from 45.2% before implementation of premedication to 28.3% after premedication initiation. At 2 years, 82.9% of patients remained on therapy, while 17.1% discontinued treatment, most commonly due to cognitive decline/progression of Alzheimer disease or ARIA progression.
Study Author Conclusions

Our findings suggest that ARIA is a significant concern especially in patients who are ε4 homozygous. Close monitoring of patients who are ε4 carriers is recommended to recognize any complications that may ensue.
Critique

The study provides valuable insights into the incidence of ARIA and adverse events associated with lecanemab over a two-year period. However, the retrospective design and lack of a control group may limit the ability to establish causality. Additionally, the study's findings may not be generalizable beyond the specific population studied at the Norton Neuroscience Institute Memory Center.

 

References:
[1] [1] Shields LBE, Hust HS, Cooper GE, et al. Lecanemab over a two-year duration: Key insights from a regional specialty medical center. J Prev Alzheimers Dis. 2026;13(3):100489. doi:10.1016/j.tjpad.2026.100489

Lecanemab in clinical practice: real-world outcomes in early Alzheimer’s disease
Design

Real-world analysis conducted at a single tertiary hospital

N= 86
Objective

To evaluate the demographic characteristics, treatment response, and safety profile of early-stage Alzheimer’s disease (AD) patients treated with Lecanemab at the Tel Aviv Medical Center (TLVMC)
Study Groups

Younger group (≤74 years, n= 49)

Older group (≥75 years, n= 37)
Inclusion Criteria

Patients with biomarker-confirmed early-stage AD, screened via neurological evaluations, MRI, lumbar puncture or Amyloid-PET, genetic testing, and multidisciplinary team (MDT) consensus discussions
Exclusion Criteria

Homozygous for ApoE ε4, medical, neurological, or psychiatric conditions contributing to cognitive impairment, imaging exclusions, recent stroke or transient ischemic attack (TIA), severe mental illness, uncontrolled bleeding disorders, use of anticoagulants, unstable medical conditions
Methods

Lecanemab was administered intravenously at 10 mg/kg every 2 weeks without titration, with post-infusion observation and MRI surveillance after the 5th, 7th, and 14th infusions for amyloid-related imaging abnormalities (ARIA). Cognitive outcomes were monitored using the Mini-Mental State Examination (MMSE) at baseline, 6 months, and 12 months, and adverse events were recorded throughout follow-up.
Duration

November 2023 to January 2025
Outcome Measures Change in MMSE scores; incidence of ARIA, infusion-related reactions
Baseline Characteristics  

All patients who initiated Tx (N= 86)

 Patients ≤74 Years (Younger Group, n= 49) Patients ≥75 Years (Older Group, n= 37)

Age, years

 71.99 ± 8.20 66.82 ± 6.97 78.84 ± 3.05

Female

 53 (62%) 29 (59%) 24 (65%)

Mean MMSE score

 23.96 ± 2.69 24.04 ± 2.78 23.86 ± 2.60

Clinical diagnosis

MCI

Mild AD dementia

Moderate AD dementia

 

62 (72%)

24 (28%)

0 (0%)

 

33 (67.3%)

16 (32.7%)

0 (0%)

 

29 (78.4%)

8 (21.6%)

0 (0%)

Number of ApoEε4 carriers

 46 (53%) 26 (53%) 20 (54%)
Mean baseline CSF t-tau, pg/ml 569.74 ± 279.27 603.37 ± 266.95

528.52 ± 292.75
Mean baseline CSF p-tau181, pg/ml 154.17 ± 340.04

197.22 ± 461.05

 104.18 ± 39.81

Mean baseline CSF Amyloid beta 42, pg/ml

 324.89 ± 159.75 298.13 ± 152.35 358.78 ± 164.99

Abbreviations: CSF, cerebrospinal fluid; MCI, mild cognitive impairment.
Results

At 6 months, MMSE scores declined significantly overall (p= 0.009), driven by decline in the younger subgroup (p= 0.009), while no significant change was observed in the older subgroup; however, no significant MMSE change was observed over 12 months in the intention-to-treat population.
Adverse Events

ARIA occurred in 16/86 patients (18.6%), with most cases asymptomatic; one patient developed symptomatic moderate ARIA requiring steroids. Additional adverse events included infusion-related reactions in 22.1%, all mild, and 19.8% of patients discontinued treatment, including discontinuations related to ARIA, medical conditions, anticoagulation requirements, financial issues, or patient preference.
Study Author Conclusions

This real-world analysis demonstrates the feasibility and safety of Lecanemab administration for early-stage AD within a tertiary hospital setting. Establishing dedicated infrastructure enabled streamlined patient evaluations and treatment. The findings suggest a differential response across age groups, consistent with clinical trial data. Continued longitudinal follow-up is needed to assess long-term efficacy and safety.
Critique

The study provides valuable real-world insights into Lecanemab's use, highlighting the importance of infrastructure and multidisciplinary coordination. However, limitations include the small sample size, lack of a control group, and reliance on MMSE as the primary cognitive measure. The exclusion of ApoE ε4 homozygous patients may limit the generalizability of safety findings. Further research with larger cohorts and comprehensive cognitive assessments is needed to validate these findings.
References:
[1] [1] Bregman, N., Nathan, T., Shir, D. et al. Lecanemab in clinical practice: real-world outcomes in early Alzheimers disease. Alz Res Therapy 17, 119 (2025). https://doi.org/10.1186/s13195-025-01763-1

Lecanemab Treatment in a Specialty Memory Clinic
Design

Retrospective analysis

N= 234
Objective To examine the feasibility and safety of treating patients in specialty memory clinics with lecanemab
Study Groups All patients (n= 234)
Inclusion Criteria Patients with early symptomatic AD, based on FDA label and appropriate use recommendations, treated between August 1, 2023, and October 1, 2024
Exclusion Criteria Patients not meeting FDA label criteria or with conditions contraindicated by appropriate use recommendations
Methods Patients were treated with lecanemab, 10 mg/kg, intravenously every 2 weeks. Monitoring MRIs were conducted before the fifth, seventh, and fourteenth infusion. Infusion-related reactions and ARIA were assessed
Duration August 1, 2023, to October 1, 2024
Outcome Measures

Primary: Infusion-related reactions, ARIA

Secondary: Withdrawal from treatment
Baseline Characteristics   All patients (n= 234)
Mean age, years (SD) 74.4 (6.7)
Female 117 (50%)
Male 117 (50%)
Results   All patients (n= 234)
Infusion-related reactions 87 (37%)
Patients at risk for ARIA 194
Developed ARIA 42 (22%)
Developed ARIA-E with or without ARIA-H 29 (15%)
Developed isolated ARIA-H 13 (6.7%)
Developed symptomatic ARIA 11 (5.7%)
Clinically severe symptoms 2 (1.0%)
Withdrawal from treatment 23 (9.8%)
Adverse Events Infusion-related reactions occurred in 37% of patients, typically mild. ARIA developed in 22% of patients, with 5.7% experiencing symptomatic ARIA. No macrohemorrhages or deaths were observed.
Study Author Conclusions A single-specialty memory clinic initiated lecanemab treatment in 234 patients over 14 months. The frequency of significant adverse events, including ARIA, was manageable. These results may inform discussions about the risks of anti-amyloid treatments.
Critique The study demonstrates the feasibility of administering lecanemab in a clinical setting with manageable adverse events. However, the retrospective design and single-center setting may limit generalizability. The low diversity of the patient population is a significant limitation, and the study's findings may not be applicable to broader populations. Additionally, the study's short follow-up period may not capture long-term outcomes or rare adverse events.
References:
[1] [1] Paczynski M, Hofmann A, Posey Z, et al. Lecanemab Treatment in a Specialty Memory Clinic. JAMA Neurol. 2025;82(7):655-665. doi:10.1001/jamaneurol.2025.1232

 

Initial Real‑World Evidence for Lecanemab in the United States
Design

Observational study

N= 4,261
Objective

To provide information about patient demographics, clinical characteristics, provider specialty, and lecanemab utilization patterns
Study Groups

All patients (N= 4,261)
Inclusion Criteria

Patients receiving one or more lecanemab doses between January 6, 2023 and October 31, 2024, with continuous clinical activity ≥ 6 months prior to the first lecanemab infusion
Exclusion Criteria Not specified
Methods

Patient data were derived from open administrative claims within the PurpleLab database. Data collected included demographics, clinical characteristics, and treatment patterns. Treatment gaps were calculated as the number of days without lecanemab supply between consecutive infusions.
Duration

January 6, 2023 to October 31, 2024
Outcome Measures Lecanemab utilization patterns, patient demographics, clinical characteristics, provider specialty
Baseline Characteristics  

All patients (N= 4,261)

Age, years

< 65

65–69

70–74

75–79

80–85

75.2 ± 6.3

222 (5.2%)

531 (12.5%)

1,011 (23.7%)

1,386 (32.5%)

1,111 (26.1%)

Female

 2,342 (55.0%)

White

 3,314 (77.8%)

Provider specialty 

Neurology

Family medicine

Internal medicine

Geriatrics

General practice

Psychiatry

 

3,475 (81.6%)

213 (5.0%)

194 (4.6%)

84 (2.0%)

71 (1.7%)

52 (1.2%)

Key diagnosis 

Alzheimer’s disease

Mild cognitive impairment

 

3,293 (77.3%)

1,349 (31.7%)

Prevalent comorbid conditions 

Dyslipidemia

Hypertension

Sleep disorders

Dorsalgia

Other anxiety disorders

 

1,610 (37.8%)

1,391 (32.6%)

725 (17.0%)

559 (13.1%)

549 (12.9%)
Results  

All patients (N= 4,261)

Follow-up period, days

< 90

≥ 90 and < 180

≥ 180

171.1 ± 113.7

1,212 (28.4%)

1,160 (27.2%)

1,889 (44.3%)

Time from earliest Alzheimer’s disease or mild cognitive impairment diagnosis to index date, days

 79.7 ± 64.4

Number of lecanemab administrations

Per patient

Per patient per month

 

9.1 ± 9.7

1.9 ± 1.0

Time between lecanemab administrations, days

Consecutive administrations

Between 4th and 5th administrations

Between 6th and 7th administrations

Between 13th and 14th administrations

 

16.3 ± 11.0

18.0 ± 15.4

17.1 ± 10.7

16.4 ± 8.6

Time from lecanemab initiation to first follow-up MRI exam, days

 52.9 ± 37.4

Lecanemab treatment gap 

Had any ≥ 90-day gap during the follow-up period

Had any ≥ 90-day interruption and resumed treatment

 

757 (17.8%)

118 (2.8%)

Use of symptomatic Alzheimer’s disease agents 

Cholinesterase inhibitors

Memantine

Cholinesterase inhibitors and/or memantine

 

1,196 (28.1%)

701 (16.5%)

1,408 (33.0%)
Adverse Events

Not assessed
Study Author Conclusions

In summary, we found that lecanemab use in the real world followed US FDA prescribing recommendations with relatively high patient adherence over 171 days of follow-up. Furthermore, our results have confirmed that neurologists are more likely than general practitioners to prescribe monoclonal antibodies, and therefore, access may be more limited in regions where there are fewer neurologists. Finally, we have identified utilization disparities between rural and diverse populations relative to urban and White populations. Future investigations are needed to better understand the long-term treatment patterns of lecanemab in early-stage AD as well as the barriers contributing to the treatment gaps in affected populations.
Critique

The study provides valuable real-world insights into lecanemab utilization and adherence patterns. However, limitations include potential coding errors inherent to claims data, limited clinical detail, and a mean follow-up duration of less than 6 months, which may restrict assessment of long-term treatment patterns. Additionally, Alzheimer’s disease severity was not captured, limiting interpretation by disease stage, and safety outcomes were not evaluated.

 

References:
[1] Brixner DI, Zhao C, Toyosaki H, Frech FH, Rosenbloom MH. Initial Real-World Evidence for Lecanemab in the United States. Drugs Aging. 2026;43(1):69-76. doi:10.1007/s40266-025-01261-x

Updated safety results from phase 3 lecanemab study in early Alzheimer’s disease
Design

Multicenter, double-blind, placebo-controlled, parallel-group study with open-label extension (OLE)

N= 1795 (Core)

N= 1612 (Core + OLE)
Objective To evaluate the safety of lecanemab in participants with early Alzheimer's disease, focusing on adverse events such as amyloid-related imaging abnormalities (ARIA) and infusion reactions
Study Groups

Placebo (n= 897)

Lecanemab 10 mg/kg biweekly (n= 898)
Inclusion Criteria Age 50 to 90 years old; MCI due to AD or mild AD dementia; amyloid pathology confirmed by amyloid PET or CSF; objective impairment in episodic memory; screening MRI with no more than 4 microhemorrhages and no extensive white matter pathology
Exclusion Criteria Bleeding disorder not under adequate control; platelet count < 50,000; INR > 1.5 for non-anticoagulant users; unstable anticoagulant therapy
Methods Participants were randomized 1:1 to receive placebo or lecanemab 10 mg/kg biweekly. 
Duration 18-month Core study with ongoing OLE expected to last 4 years
Outcome Measures

Primary: Safety outcomes including adverse events such as ARIA and infusion reactions

Secondary: Incidence of serious adverse events (SAEs) and deaths
Baseline Characteristics   Placebo (N=897) Lecanemab (N=898) Lecanemab (N=1612)
Age, mean (SD), years 71.1 (7.8) 71.4 (7.9) 71.5 (7.8)
Female, n (%) 476 (53.1) 462 (51.4) 844 (52.4)
Caucasian, n (%) 696 (77.6) 685 (76.3) 1228 (76.2)
ApoE e4 Carrier, n (%) 611 (68.1) 620 (69.0) 1117 (69.3)
Mild dementia due to AD, n (%) 342 (38.1) 346 (38.5) 607 (37.7)
Mild cognitive impairment, n (%) 555 (61.9) 552 (61.5) 1005 (62.3)
Results   Placebo (N=897) Lecanemab (N=898) Lecanemab (N=1612)
Any adverse event 735 (81.9%) 798 (88.9%) 1389 (86.2%)
Deaths 7 (0.8%) 6 (0.7%) 16 (1.0%)
Serious adverse event (SAE) 101 (11.3%) 126 (14.0%) 241 (15.0%)
ARIA-E 15 (1.7%) 113 (12.6%) 219 (13.6%)
ARIA-H 80 (8.9%) 152 (16.9%) 298 (18.5%)
Adverse Events The most common adverse events in the lecanemab group (> 10%) were infusion-related reactions (24.5%), ARIA-H microhemorrhages (16.0%), COVID-19 (14.7%), ARIA-E (13.6%), and headache (10.3%). ARIA-E and ARIA-H were largely radiographically mild-to-moderate.
Study Author Conclusions Lecanemab was generally well-tolerated, with the most common adverse events being infusion-related reactions, ARIA-H, and ARIA-E. Clinicians, participants, and caregivers should understand the incidence, monitoring, and management of these events for optimal patient care.
Critique The study provides comprehensive safety data on lecanemab, highlighting its tolerability and the incidence of ARIA. However, the study's reliance on MRI for ARIA monitoring may not capture all clinical symptoms, and the long-term safety profile remains to be fully understood. The study's design and large sample size are strengths, but the potential for selection bias and the need for further research on long-term effects are limitations.
References:
[1] [1] Honig LS, Sabbagh MN, van Dyck CH, et al. Updated safety results from phase 3 lecanemab study in early Alzheimer's disease. Alzheimers Res Ther. 2024;16(1):105. Published 2024 May 10. doi:10.1186/s13195-024-01441-8

High Early Parenteral Lipid in Very Preterm Infants: A Randomized-Controlled Trial
Design

Randomized controlled trial post-hoc analysis

N= 83
Objective To determine whether high early parenteral soybean oil lipid intake in very low birth weight (VLBW) infants in the first week after birth decreases the proportion of weight loss and subsequently the incidence of extrauterine growth restriction (EUGR)
Study Groups

Control group (n= 38)

High lipid intake group (n= 45)
Inclusion Criteria Infants born <32 completed weeks of gestation and weighing <1500 g, eligible for enrollment within 6 hours of birth
Exclusion Criteria Small for gestational age (birth weight <10th percentile), major congenital or chromosomal anomalies, anticipated parenteral nutrition <7 days, culture-proven early-onset sepsis, suspected or confirmed biliary atresia
Methods The intervention group started on 2 g/kg per day of 20% IVLEs, increased to 3 g/kg per day the next day. The control group started at 0.5-1 g/kg per day, increased daily by 0.5-1 g/kg per day until reaching 3 g/kg per day. Monitoring for serum triglyceride was performed after 24 hours of each lipid increment.
Duration August 2018 to October 2019
Outcome Measures

Primary: Proportion of postnatal weight loss

Secondary: Incidence of EUGR, lipid tolerance, impact on parenteral protein and carbohydrate intakes
Baseline Characteristics   Control group (n = 38) High lipid intake group (n = 45)
Gestational age, wk, mean (SD) 27.3 (2.4) 27.1 (2.3)
Birth weight, g, mean (SD) 1011 (250) 1019 (271)
Apgar 5 min, median (IQR) 8 (6, 8) 8 (7, 8)
Male sex, n (%) 25 (65.8) 28 (62.2)
Multiple birth, n (%) 9 (23.7) 16 (35.6)
Antenatal steroid (any), n (%) 35 (92.1) 44 (97.8)
Cesarean delivery, n (%) 25 (65.8) 35 (77.8)
Use of surfactant, n (%) 20 (52.6) 20 (44.4)
Mechanical ventilation, n (%) 24 (63.2) 24 (53.3)
Results   Control group (n = 38) High lipid intake group (n = 45) p-value
Age of starting lipid, h, mean (SD) 17.5 (7.8) 13.8 (7.8) 0.03
Maximal percentage of weight loss, mean (SD) 12.7 (4.6) 10.4 (3.6) 0.02
Extra-uterine growth restriction, n (%) 25 (67.6) 17 (38.6) 0.009
Head circumference z scores, mean (SD) -1.59 (0.98) -1.09 (0.96) 0.04
Triglyceride level, mmol/L, mean (SD) 1.49 (0.5) 1.91 (0.8) 0.007
Adverse Events Four infants in the experimental group developed cholestasis, and none in the control group. Hypertriglyceridemia was similar between the two groups.
Study Author Conclusions In VLBW infants, provision of a high early dose of parenteral lipid in the first week of age results in less weight loss and lower incidence of EUGR.
Critique The study was limited by its single-center design and lack of blinding. It did not include body composition measurements to identify fat and lean body masses at discharge. The arbitrary cut-off for triglyceride levels as a measure of lipid tolerance may not be well-supported by existing literature.
References:
[1] Costa T, Premi E, Liloia D, Cauda F, Manuello J. Unleashing the Power of Bayesian Re-Analysis: Enhancing Insights into Lecanemab (Clarity AD) Phase III Trial Through Informed t-Test. J Alzheimers Dis. 2023;95(3):1059-1065. doi:10.3233/JAD-230589

 

Long-term safety and efficacy of lecanemab in early Alzheimer’s disease: Results from the clarity AD open-label extension study
Design

Open-label extension study following an 18-month randomized, placebo-controlled core phase

N= 1616
Objective

To evaluate the long-term safety, efficacy, and health-related quality of life (HRQoL) outcomes of lecanemab in early Alzheimer's disease over 36 months
Study Groups

Early start lecanemab (n= 898)

Delayed start lecanemab (n= 718)
Inclusion Criteria

Participants aged 50 to 90 years with mild cognitive impairment due to AD or mild AD dementia based on NIA-AA criteria, confirmed amyloid pathology by PET or CSF, and completed the Core Clarity AD study
Exclusion Criteria

Significant medical conditions that would interfere with study conduct
Methods

Participants received open-label lecanemab 10 mg/kg IV biweekly. Clinical and HRQoL outcomes were evaluated, with subgroup analyses for low pathology (low baseline amyloid or tau). Safety evaluations included adverse events, vital signs, and MRI safety parameters. Efficacy was compared to an ADNI cohort.
Duration

36 months
Outcome Measures

Primary: Incidence of adverse events, changes in vital signs, and MRI safety parameters

Secondary: Change in CDR-SB, amyloid PET, ADAS-Cog14, ADCOMS, ADCS-MCI-ADL, HRQoL measures (EQ-5D-5L, Qol-AD, ZBI)
Baseline Characteristics   Early start (n= 898)

Delayed start (n= 718)
Age, years 71.4 ± 7.9 71.0 ± 7.8
Female 443 (51.6%) 464 (53.0%)
Caucasian 655 (76.3%) 677 (77.4%)
ApoE e4 carrier 592 (68.9%) 600 (68.6%)
Results   Early start (n= 898)

Delayed start (n= 718)

 p-value
CDR-SB change from baseline

-1.44

 -1.10 <0.001
Amyloid PET change from baseline

-55.5 Centiloids

 -50.0 Centiloids <0.001
ADAS-Cog14 change from baseline

-3.2

 -2.8 <0.001
Adverse Events

No new safety signals observed. ARIA rates were low after 6 months and similar to placebo. Overall incidence of adverse events was 91.6% with an EAR of 42.5 per 100 subject-years.
Study Author Conclusions

Lecanemab treatment continues to provide benefits up to 36 months, supporting early initiation and long-term treatment in early Alzheimer's disease. No new safety concerns were identified, and ARIA rates were low and similar to placebo after 6 months.
Critique

The study's open-label design in the extension phase may introduce bias, and the use of historical controls for some analyses could lead to confounding factors. However, the study provides valuable long-term data on lecanemab's efficacy and safety, supporting its use in early Alzheimer's disease.

 

References:
[1] [1] van Dyck CH, Sperling R, Johnson K, et al. Long-term safety and efficacy of lecanemab in early Alzheimer's disease: Results from the clarity AD open-label extension study. Alzheimers Dement. 2025;21(12):e70905. doi:10.1002/alz.70905

 

Lecanemab for treatment of individuals with early Alzheimer’s Disease (AD) who are apolipoprotein E ε4 (ApoE ε4) non-carriers or heterozygotes
Design

Randomized, controlled trial (core) with an open-label extension phase (OLE)

N= 1795
Objective

To present efficacy and safety results in ApoE ε4 non-carriers or heterozygotes population of Clarity AD
Study Groups

i) Clarity AD All Participants:

Placebo (n= 897)

Lecanemab 10 mg/kg biweekly (n= 898)

ii) ApoE ε4 non-carriers or heterozygotes (EMA Indicated Population):

Placebo (n= 764)

Lecanemab 10 mg/kg biweekly (n= 757)

iii) ApoE ε4 non-carriers or heterozygotes (United Kingdom indicated population):

Placebo (n= 743)

Lecanemab 10 mg/kg biweekly (n= 723)
Inclusion Criteria Participants with early AD who are ApoE ε4 non-carriers or heterozygotes
Exclusion Criteria ApoE ε4 homozygotes
Methods

Participants were randomized to placebo or lecanemab 10 mg/kg IV biweekly. Efficacy endpoints included changes in CDR-SB, amyloid PET, ADAS-Cog14, and ADCS-MCI-ADL. Safety was monitored through adverse events, changes in vital signs, ECGs, laboratory safety tests and ARIA occurrence. Biomarker assessments included plasma Aβ 42/40 ratio and p-tau181.
Duration

18 months for core study, up to 36 months for OLE
Outcome Measures

Primary: Change in CDR-SB

Secondary: Change in amyloid PET, ADAS-Cog14, ADCS-MCI-ADL, Safety, biomarker and HRQoL assessments
Baseline Characteristics  

ApoE ε4 Heterozygotes or Non-carriers Population
EMA Indicated Population

United Kingdom indicated population

Placebo (n= 764)

 Lecanemab (n= 757) Placebo (n= 743) Lecanemab (n= 723)
Age, years 71.5 ± 8.0 72.1 ± 7.9 71.4 ± 8.0 72.1 ± 7.9
Female, n (%) 401 (52.5%) 383 (50.6%) 390 (52.5%) 365 (50.5%)

AD stage:

MCI

Mild dementia

 

472 (61.8%)

292 (38.2%)

 

466 (61.6%)

291 (39.4%)

 

462 (62.2%)

281 (37.8%)

 

445 (61.5%)

278 (38.5%)

ApoE4 status, Noncarrier

286 (37.4%)

278 (36.7%)

275 (37.0%)

267 (36.9%)

Mean ADAS-Cog14

24.40

24.46

24.40

24.48

Mean ADCS MCI-ADL

40.7

41.2

40.9

41.3
Results   Placebo

Lecanemab

 p-value
CDR-SB change from baseline at 18 months 1.75 1.22 <0.00001
Amyloid PET change from baseline at 18 months - -59.4 <0.00001
Biomarker assessment, Plasma Aβ42/40 ratio (at 18 months)  - 0.008  <0.00001 
Biomarker assessment, Plasma p-tau181 (at 18 months) -  0.825 <0.00001 
Adverse Events (Safety)

Serious adverse events occurred in 14.8% with lecanemab vs 11.3% with placebo. Overall adverse events were 88.1% vs 81.2%, with drug withdrawals in 5.9% vs 3.0%. Infusion reactions (25.8% vs 7.1%), ARIA-H (12.9% vs 6.8%), and ARIA-E (8.9% vs 1.3%) were more frequent with lecanemab. Intracerebral hemorrhage was rare (0.4% vs 0.1%).
Quality of Life

Lecanemab preserved HRQoL, with 43–53% less decline in EQ-5D-5L and QOL-AD, and 39% lower caregiver burden (ZBI) vs placebo. Benefits persisted through 36 months in the OLE.
Study Author Conclusions

In the ApoE ε4 heterozygotes or non-carrier subgroup of Clarity AD, lecanemab slowed decline in disease progression and reduced markers of amyloid, with expanding benefit over time.
Critique

The study's post-hoc and exploratory nature limits the strength of conclusions. The exclusion of ApoE ε4 homozygotes may limit generalizability. The study shows promising results for early treatment initiation, but longer-term controlled data are lacking.

 

References:
[1] [1] Perry R, Kipps C, Soto Martn ME, et al. Lecanemab for treatment of individuals with early Alzheimer's Disease (AD) who are apolipoprotein E 4 (ApoE 4) non-carriers or heterozygotes. J Prev Alzheimers Dis. 2026;13(4):100507. doi:10.1016/j.tjpad.2026.100507