Initial real‐world experience with lecanemab prescribing patterns in Japan: The Longevity Improvement & Fair Evidence (LIFE) Study

Abstract

Introduction

Lecanemab, an anti‐amyloid‐beta antibody, is approved in over 40 countries. Patient demographic data exist for the US but are limited elsewhere. This study examined early real‐world lecanemab use in Japan.

Methods

Using claims data from 18 municipalities, we identified patients prescribed lecanemab between December 2023 and September 2024. The study outcome was the discontinuation rate, with discontinuation defined as a ≥42‐day prescription gap. Covariates included age, sex, long‐term care certification, municipality size, comorbidities, Mini‐Mental State Examination (MMSE) score, and Clinical Dementia Rating (CDR).

Results

We identified 123 lecanemab recipients (median age: 76 years, interquartile range: 73–79 years; women: 73.2%). Most had mild impairment: 60.9% with MMSE ≥24 and 79.3% with CDR 0.5. The discontinuation rate was 1.04/100 person‐months, with most occurring within 1.5 months.

Discussion

In this first Asian report, lecanemab was mainly prescribed to older women with milder cognitive impairment. Early discontinuation may reflect cautious adoption in Japan.

Highlights

• This study provides the first real‐world data on lecanemab use in Asia.

• Most patients were women in their 70s with mild cognitive impairment.

• Discontinuations occurred at 1.04/100 person‐months, mainly within 1.5 months.

• Lecanemab was prescribed mainly to those without LTC and with mild impairment.

1. Background

Lecanemab is a monoclonal antibody directed against soluble and insoluble forms of amyloid‐beta. A phase 3 trial demonstrated significant reductions in brain amyloid accumulation and moderate slowing of cognitive and functional decline in patients with mild cognitive impairment or mild Alzheimer's disease. ¹ Lecanemab was first approved in the US in July 2023, followed by approval in Japan in September 2023. It has been approved in more than 40 countries globally as of August 2025. ²

RESEARCH IN CONTEXT

1. Systematic review: We searched PubMed and reviewed the literature on lecanemab use. While phase 3 trial data are well established, real‐world evidence is limited. US studies have described prescribing patterns and short‐term discontinuation, but no reports from Asian populations under universal healthcare are available.

2. Interpretation: In this first Asian cohort study on lecanemab use, this drug was most often prescribed to women in their mid‐70s with milder cognitive impairment. The discontinuation rate was 1.04/100 person‐months, with most discontinuations occurring within 1.5 months. Our results align with US findings and suggest cautious early adoption in Japan.

3. Future directions: Future studies should clarify the factors associated with lecanemab discontinuation and examine longer‐term patterns of treatment persistence. Comparative analyses across countries and healthcare systems may further reveal differences in prescribing behavior and patient characteristics, providing insights beyond early adoption in Japan.

Although recent studies have described the demographic characteristics of lecanemab recipients in the US, ³ , ⁴ there have been no such reports from other countries. Emerging evidence suggests that the prevalence of Alzheimer's disease and abnormal amyloid biomarkers in individuals with similar cognitive diagnoses can differ among racial and ethnic groups, even though diagnostic thresholds themselves are generally consistent across groups. ⁵ Such variations may contribute to racial differences in eligibility for lecanemab use. Moreover, as lecanemab is a high‐cost medication, its prescribing patterns may also be influenced by differences in healthcare systems. This study aimed to characterize previously unreported aspects of lecanemab use (including comorbidities, cognitive function, and prescribing patterns) in Japan, an Asian country with universal healthcare.

2. Methods

2.1. Study design

The overall design of this cohort study is illustrated in Supplementary Figure A. The study outcome was the discontinuation rate of lecanemab prescriptions. The study period spanned from December 2023 (when lecanemab became available for prescription in Japan) through the most recent month of data available in each municipality at the time of analysis (ranging from March to September 2024). The follow‐up period was defined as the time from each patient's initial lecanemab prescription to either the discontinuation date (last prescription date) or the last recorded claims date, whichever was earlier.

FIGURE 1.

Flow diagram of patient selection. CDR, Clinical Dementia Rating; LTC, long‐term care; MMSE, Mini‐Mental State Examination.

2.2. Study setting

This study utilized data from the Longevity Improvement & Fair Evidence (LIFE) Study, a population‐based longitudinal database managed by Kyushu University (Fukuoka, Japan). ⁶ , ⁷ The LIFE Study compiles health and welfare–related data from participating municipalities across Japan, with an emphasis on inpatient and outpatient medical claims. All data are linked at the individual level through unique anonymized identifiers. The data include individuals enrolled in either the National Health Insurance program (covering the self‐employed, part‐time employed, unemployed, and primary industry workers aged ≤74 years) or the Latter‐Stage Older Persons Health Care System (covering residents aged ≥75 years). These public insurance programs are administered by municipal governments.

In accordance with Japanese guidelines, all medical institutions included in this study had met the nationally standardized eligibility criteria for prescribing lecanemab. ⁸ These criteria include the presence of multiple board‐certified neurologists, geriatricians, psychiatrists, or neurosurgeons with extensive experience in dementia care; completion of training on amyloid‐related imaging abnormality assessment and magnetic resonance imaging interpretation; availability of ≥1.5‐tesla magnetic resonance imaging scanners; and the capability to confirm amyloid pathology by positron emission tomography or cerebrospinal fluid examination, either in‐house or through partner facilities. Given this high degree of standardization across prescribing institutions, facility‐level information was not presented in this study.

The study was conducted in compliance with the Declaration of Helsinki and approved by the Kyushu University Institutional Review Board for Clinical Research (Approval No. 226530).

2.3. Study cohort

The study included 18 municipalities for which the required information was available throughout the study period. Patients who received a prescription for lecanemab during the study period were identified using the Anatomical Therapeutic Chemical classification code N06DX04. To ensure a 6‐month look‐back period, individuals whose first available claims record occurred less than six months prior to their initial lecanemab prescription were excluded from analysis.

2.4. Outcome

Lecanemab is administered via intravenous infusion every two weeks. However, short delays of about one week are common, and may occur for reasons unrelated to lecanemab itself. To avoid misclassifying such short delays as treatment discontinuation, we defined this outcome as a gap of ≥42 days between claims for lecanemab. In addition, we conducted a supplementary analysis in which treatment pause was defined as a gap of ≥28 days between claims for lecanemab.

2.5. Covariates

We identified the following covariates at the time of lecanemab initiation: age (originally extracted as a quantitative variable but presented in 5‐year categories in Table 1), sex, long‐term care (LTC) certification, municipality size, comorbidities, and two cognitive function assessments: Mini‐Mental State Examination (MMSE) score and Clinical Dementia Rating (CDR). LTC certifications are issued by municipal governments based on an individual's degree of physical/cognitive impairment and care needs level, and certified individuals are eligible to use services under the LTC insurance system. Next, we categorized the municipality in which each patient had initiated lecanemab treatment according to population size: large (≥500,000), medium (200,000–499,999), and small (< 200,000). ⁹ Comorbidities were identified using their corresponding International Classification of Diseases, 10th Revision (ICD‐10) codes, with a focus on common conditions among older adults (Supplementary Table A). A comorbidity was considered present if the relevant ICD‐10 code appeared at least once during the six months preceding the first lecanemab prescription. In Japan, MMSE and CDR evaluations are required at the time of initiating lecanemab therapy, and must be recorded in the insurance claims data as supplemental information. However, a preliminary analysis of the data found that some of these evaluations were recorded in the month after lecanemab initiation. Therefore, we included records of MMSE and CDR for up to one month after initiation.

TABLE 1.

Baseline characteristics of lecanemab recipients.

	Overall
N	123 (%)
Sex—women	90 (73.2)
Age (years)
≤59	4 (3.3)
60–64	3 (2.4)
65–69	11 (8.9)
70–74	24 (19.5)
75–79	51 (41.5)
80–84	26 (21.1)
≥85	4 (3.3)
Follow‐up duration (days), median [IQR]	68.0 [21.5, 118.0]
Event: Lecanemab discontinuation	3 (2.4)
Municipality size (by population)
Large (≥500,000)	104 (84.6)
Medium (200,000–499,999)	4 (3.3)
Small (< 200,000)	15 (12.2)
Comorbidities
Hypertension	69 (56.1)
Diabetes mellitus	33 (26.8)
Stroke	34 (27.6)
Depression	19 (15.4)
Heart failure	15 (12.2)
Thyroid disease	16 (13.0)
Chronic kidney disease	13 (10.6)
Parkinson's disease	8 (6.5)
Peripheral artery disease	3 (2.4)
COPD	3 (2.4)
Rheumatoid arthritis	1 (0.8)
LTC certification
Certified	10 (11.2)
MMSE score
22–23	34 (39.1)
24–30	53 (60.9)
CDR
0.5	69 (79.3)
1	18 (20.7)

Values are presented as n (%) unless stated otherwise.

LTC certification data were available for 89 of 123 patients (72.4%), and MMSE and CDR data were available for 87 of 123 patients (70.7%). The proportions for LTC certification, MMSE score, and CDR were calculated using patients without missing values.

Abbreviations: CDR, Clinical Dementia Rating; COPD, chronic obstructive pulmonary disease; IQR, interquartile range; LTC, long‐term care; MMSE, Mini‐Mental State Examination. CDR, Clinical Dementia Rating; COPD, chronic obstructive pulmonary disease; IQR, interquartile range; LTC, long‐term care; MMSE, Mini‐Mental State Examination.

2.6. Statistical analysis

First, the baseline characteristics of the patients were described using numbers with percentages for categorical variables and median values with interquartile ranges (IQRs) for continuous variables.

Next, the crude discontinuation rates of lecanemab were calculated per 100 person‐months. The cumulative incidence of discontinuation was then estimated using the Kaplan–Meier method, with group comparisons assessed using log‐rank tests. These analyses were performed for the overall cohort and stratified by key covariates in subgroup analyses. Due to the limited number of LTC‐certified individuals, the subgroup analysis for LTC certification was conducted based on whether or not a patient had any LTC certification, rather than by individual care needs levels. For the MMSE subgrouping, a cutoff of 24 was used due to the small number of patients with MMSE scores of ≥28.

LTC information was unavailable in five municipalities, and MMSE and CDR data were unavailable in one municipality. Because the missingness mechanism for these variables was judged to be neither missing completely at random nor missing at random, individuals from these municipalities were excluded from the corresponding subgroup analyses. Additionally, MMSE and CDR values were missing in some patients even from municipalities where such data were available. To calculate the lecanemab discontinuation rates, these missing values were imputed using predictive mean matching, which generated five imputed datasets. The results for MMSE and CDR were summarized as means and standard deviations. However, Kaplan–Meier analyses were performed using only complete cases. To assess the potential direction of bias due to missing data on LTC, MMSE, and CDR, we compared baseline characteristics between patients with and without these data items. In addition, to evaluate the impact of shortened observation periods for reasons other than the occurrence of events, we calculated the total follow‐up duration (until the last recorded claims) among patients who discontinued lecanemab.

Given the limited number of events, the alpha level for the log‐rank test was set at 0.1. All preprocessing, statistical analyses, and data visualizations were conducted using R software version 4.2.1 (R Foundation for Statistical Computing, Vienna, Austria).

3. RESULTS

3.1. Patient characteristics

We analyzed 123 lecanemab recipients from 18 municipalities (Figure  1 ). Their baseline characteristics are summarized in Table 1. The majority were women (n = 90, 73.2%), and the median age was 76 years (IQR: 73–79). The median total follow‐up duration was 68 days (IQR: 21.5–118.0). MMSE scores were < 24 in 34 patients (39.1% in patients without missing values) and ≥24 in 53 patients (60.9%). Most patients had a CDR of 0.5 (n = 69, 79.3%). The majority of patients had initiated lecanemab treatment in large municipalities (n = 104, 84.6%). The most prevalent comorbidity was hypertension (56.1%), followed by stroke (27.6%), diabetes mellitus (26.8%), and depression (15.4%).

3.2. Discontinuation rate of lecanemab

Three patients (2.4%) discontinued lecanemab during the study period. The overall crude discontinuation rate was 1.04/100 person‐months (0.91 in women and 1.46 in men). The discontinuation rate for patients without LTC certification was 1.63/100 person‐months. When analyzed according to cognitive function category, the mean discontinuation rates per 100 person‐months were 1.18 (standard deviation: 0.10) for MMSE score < 24, 0.99 (0.04) for MMSE score ≥24, and 1.33 (0.01) for CDR 0.5. Cumulative incidence curves indicated that lecanemab discontinuation predominantly occurred within 1.5 months of treatment initiation (Figure  2A–F ). None of the subgroups showed significant differences (Figure  2B–F ). The median total follow‐up duration for patients who discontinued lecanemab was 85.0 days (IQR: 70.0–123.5).

FIGURE 2.

Cumulative incidence of lecanemab discontinuation. (A) In the overall cohort, lecanemab discontinuation events occurred predominantly within 45 days from the initial prescription. (B) No clear difference in discontinuation was observed between men and women. (C) No clear difference in discontinuation was observed between patients aged ≥75 and < 75 years. (D) No discontinuation events occurred among patients with LTC certification, but events were observed in those without certification. (E) There was no apparent difference in discontinuation between patients with MMSE scores ≤23 (suggesting cognitive impairment) and ≥24 (suggesting milder cognitive impairment). (F) Discontinuation was only observed among those with a CDR of 0.5 (indicating very mild cognitive impairment). CDR, Clinical Dementia Rating; LTC, long‐term care; MMSE, Mini‐Mental State Examination.

In a supplementary analysis using a ≥28‐day gap, ten patients met the criterion (Supplementary Figure B); among the seven patients who met the ≥28‐day criterion but not the ≥42‐day criterion, one reached the end of follow‐up within 42 days and was censored, and the other six resumed treatment before 42 days. Consistent with the main analysis, all events in the supplementary analysis occurred within 1.5 months of treatment initiation.

3.3. Comparisons between patients with and without missing data

The baseline characteristics of patients according to LTC data availability and MMSE/CDR data availability are summarized in Supplementary Tables B and C, respectively. Missing LTC data were more frequent among women and patients aged ≥80 years (Table B). In addition, patients with missing LTC data had shorter follow‐up durations. For MMSE and CDR, missing data were observed in two patients from municipalities lacking these data, and in 34 patients from municipalities with available data. No major differences in age or follow‐up duration were observed between patients with and without missing MMSE or CDR data (Table C).

4. Discussion

This cohort study provides an initial characterization of lecanemab prescribing patterns during the early post‐initiation phase in a Japanese population. Most recipients were women in their mid‐70s with milder cognitive impairment. The overall discontinuation rate was 1.04/100 person‐months, with most discontinuations occurring within 1.5 months.

A US study reported a short‐term lecanemab discontinuation rate below 10%. ⁴ In our cohort, the corresponding discontinuation rate was even lower, and discontinuation occurred almost entirely within 1.5 months of treatment initiation in our cohort. The prevalences of comorbidities generally matched those of typical older populations in Japan, ¹⁰ , ¹¹ , ¹² and hypertension has similarly been found to be common among lecanemab recipients in a US medical center. ¹³ In another aspect, our analysis of MMSE score and CDR—information not available in previous real‐world studies—indicated that lecanemab tends to be prescribed to patients with relatively mild cognitive impairment. This may reflect clinicians’ adherence to the approved indication for lecanemab, which targets patients with early Alzheimer's disease. Furthermore, physicians may be more inclined to initiate treatment in patients with less cognitive impairment, anticipating greater potential benefit and lower risk. Alternatively, this trend could indicate a cautious approach in clinical practice, wherein lecanemab is initially prescribed to milder cases before expanding its use to more severe stages as experience accumulates. This hypothesis is further supported by the observation that approximately 90% of our participants had not been certified for any level of LTC.

As Japan has set nationally standardized eligibility criteria for institutions to prescribe lecanemab, ⁸ all patients in our study were treated at similar facilities. Although most patients were from large municipalities, this likely reflects both the urban consolidation of institutions eligible to administer lecanemab and the larger underlying populations, suggesting a greater pool of potentially eligible patients. Comparisons of lecanemab prescribing patterns by municipality size would require rigorous adjustment for background factors, but our small sample precluded such analyses. Socioeconomic factors, including income and educational attainment, may also influence access to high‐cost therapies such as lecanemab. However, these variables were not available in our dataset. These issues highlight the need for further investigations with larger samples and richer socioeconomic data.

Missingness in LTC information was clustered in specific municipalities and coincided with shorter follow‐up durations, suggesting potentially informative (nonrandom) missingness driven by municipality‐level data windows rather than patient factors. Consequently, estimates that condition on LTC status should be interpreted with caution because differential follow‐up can distort both effect estimates and cumulative events. In contrast, MMSE/CDR missingness was limited and largely independent of municipality, reducing concerns about major bias from these assessments. Future work should coordinate data capture across municipalities and prespecify strategies for informative missingness.

This study has several limitations. First, the short follow‐up period and small sample size limit the generalizability of our findings. These factors may have resulted in censoring bias that contributed to the relatively high frequency of lecanemab discontinuation observed in the early phase after initiation. Second, we were unable to determine the reasons for treatment discontinuation. Although claims data include diagnostic and procedural information that could potentially allow for the inference of adverse events or burden‐related discontinuation, we did not perform such analyses in this study. This is because our primary focus was to describe discontinuation rates and patient characteristics rather than to assess treatment tolerability or safety. The inability to determine reasons for discontinuation remains a significant limitation and highlights a critical area for future research. Third, missing data for LTC certification, MMSE scores, and CDR may have introduced selection bias. MMSE/CDR data were sometimes recorded after the month of initiation, but the study data did not include the operational information needed to determine the reasons for missingness.

In conclusion, our findings provide valuable insights into early lecanemab prescribing patterns and patient characteristics in an Asian population under universal healthcare coverage.

CONFLICT OF INTEREST STATEMENT

The study was partially funded by Eisai Co., Ltd. and Biogen. However, the sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. No other disclosures were reported.

CONSENT STATEMENT

This study employed an opt‐out consent process under institutional review board approval. Information on the study and contact details of the study office were publicly disclosed on the institution's website. Individuals could refuse inclusion at any time by contacting the study office, and all opt‐outs were excluded prior to analysis. All data were de‐identified before analysis, and written informed consent was waived in accordance with national guidelines due to the minimal‐risk use of de‐identified data.

Supporting information

Supporting Information

Supporting Information