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Peer-reviewedCC BY-NC-ND 4.0Alzheimer's Research & Therapy

Real-world effectiveness of monoclonal antibody lecanemab versus acetylcholinesterase inhibitors in Alzheimer’s disease: a target trial emulation

  • Chuo-Yu Lee1,2
  • Chih-Wei Hsu3
  • Ping-Tao Tseng4,5,6,7
  • Yi-Ya Fang8,9
  • Brendon Stubbs10
  • Trevor Thompson11
  • Andre F. Carvalho12
  • Yu-Hsuan Lin13,14,15
  • Yu-Chen Kao16,17
  • Fu-Chi Yang18
  • Tien-Wei Hsu19,20,21
  • Chih-Sung Liang16,17
21 affiliations
  1. 1Department of Neurology, Mackay Memorial Hospital, Taipei, Taiwan
  2. 2Department of Medicine, Mackay Medical University, New Taipei City, Taiwan
  3. 3Department of Psychiatry, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
  4. 4Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
  5. 5Department of Psychology, College of Medical and Health Science, Asia University, Taichung, Taiwan
  6. 6Prospect Clinic for Otorhinolaryngology & Neurology, Kaohsiung, Taiwan
  7. 7Institute of Precision Medicine, National Sun Yat-Sen University, Kaohsiung City, Taiwan
  8. 8Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
  9. 9Department of Psychiatry, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
  10. 10Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK
  11. 11Centre for Chronic Illness and Ageing, University of Greenwich, London, UK
  12. 12IMPACT (Innovation in Mental and Physical Health and Clinical Treatment) Strategic Research Centre, School of Medicine, Barwon Health, Deakin University, Geelong, VIC Australia
  13. 13Institute of Population Health Sciences, National Health Research Institutes, Miaoli County, Taiwan
  14. 14Department of Biomedical Sciences and Engineering, National Central University, Taoyuan, Taiwan
  15. 15Department of Psychiatry, College of Medicine, National Taiwan University, Taipei, Taiwan
  16. 16Department of Psychiatry, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan
  17. 17Department of Psychiatry, Beitou Branch, Tri-Service General Hospital, No. 60, Xinmin Road, Beitou District, Taipei City, 112 Taiwan
  18. 18Department of Neurology, Tri-Service General Hospital, National Defense Medical University, Taipei, Taiwan
  19. 19Department of Psychiatry, E-DA Dachang Hospital, I-Shou University, No. 305, Dachang 1St Rd., Sanmin District, Kaohsiung City, 807 Taiwan
  20. 20Department of Psychiatry, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan
  21. 21School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
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Abstract

Background: Acetylcholinesterase inhibitors (AChEIs) provide symptomatic relief in Alzheimer’s disease (AD), whereas lecanemab may modify disease progression; however, real-world evidence on its safety and clinical impact remains limited. Therefore, this study aimed to compare the safety and effectiveness of initiating lecanemab versus AChEIs in patients with mild cognitive impairment (MCI) or AD.

Methods: Using the TriNetX US electronic health record network, we conducted a retrospective cohort study including individuals diagnosed with MCI or AD between July 2023 and September 2025. A target trial emulation with 1:1 propensity score matching and Cox models estimated comparative risks.

Results: Lecanemab was associated with a fivefold higher incidence of neuroimaging abnormalities than AChEIs, while 1-year treatment persistence was similar (53.4% vs 52.5%). After matching, 589 patients were included in each cohort. Compared with AChEIs, lecanemab was associated with significantly lower risks of behavioral and psychological symptoms of dementia (BPSD) (HR, 0.52; 95% CI, 0.36–0.77) and emergency visits (HR, 0.66; 95% CI, 0.51–0.85), but a higher risk of hospitalization (HR, 1.31; 95% CI, 1.03–1.67). Lecanemab was also associated with lower use of antipsychotics (HR, 0.47; 95% CI, 0.32–0.70), antidepressants (HR, 0.60; 95% CI, 0.43–0.85), melatonin/orexin antagonists (HR, 0.61; 95% CI, 0.42–0.88), antibiotics (HR, 0.61; 95% CI, 0.44–0.86), and antifungals (HR, 0.57; 95% CI, 0.37–0.88), whereas steroid use was higher among lecanemab users (HR, 2.19; 95% CI, 1.55–3.10).

Conclusions: Compared with an AChEI-based conventional care strategy, lecanemab initiation was associated with comparable treatment persistence and lower observed risks of BPSD, emergency visit as well as reduced use of psychotropic and infection-related medications in exploratory analyses. However, the higher incidence of neuroimaging abnormalities associated with lecanemab, along with increased risks of hospitalization and corticosteroid use, likely reflects proactive clinical monitoring and management of amyloid-related imaging abnormalities (ARIA). While residual confounding cannot be excluded and results warrant cautious interpretation, these exploratory findings warrant further validation in biomarker-confirmed cohorts and head-to-head randomized trials.

Graphical Abstract:

Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13195-026-02095-4.

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Cite

BibTeXRIS
BibTeX
@article{lee2026realworld,
  title = {{Real-world effectiveness of monoclonal antibody lecanemab versus acetylcholinesterase inhibitors in Alzheimer’s disease: a target trial emulation}},
  author = {Chuo-Yu Lee and Chih-Wei Hsu and Ping-Tao Tseng and Yi-Ya Fang and Brendon Stubbs and Trevor Thompson and Andre F. Carvalho and Yu-Hsuan Lin and Yu-Chen Kao and Fu-Chi Yang and Tien-Wei Hsu and Chih-Sung Liang},
  journal = {Alzheimer's Research \& Therapy},
  year = {2026},
  month = jun,
  doi = {10.1186/s13195-026-02095-4},
  url = {https://doi.org/10.1186/s13195-026-02095-4},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Real-world effectiveness of monoclonal antibody lecanemab versus acetylcholinesterase inhibitors in Alzheimer’s disease: a target trial emulation
AU  - Chuo-Yu Lee
AU  - Chih-Wei Hsu
AU  - Ping-Tao Tseng
AU  - Yi-Ya Fang
AU  - Brendon Stubbs
AU  - Trevor Thompson
AU  - Andre F. Carvalho
AU  - Yu-Hsuan Lin
AU  - Yu-Chen Kao
AU  - Fu-Chi Yang
AU  - Tien-Wei Hsu
AU  - Chih-Sung Liang
PY  - 2026
DA  - 2026/06/22
JO  - Alzheimer's Research & Therapy
DO  - 10.1186/s13195-026-02095-4
UR  - https://doi.org/10.1186/s13195-026-02095-4
AB  - Background: Acetylcholinesterase inhibitors (AChEIs) provide symptomatic relief in Alzheimer’s disease (AD), whereas lecanemab may modify disease progression; however, real-world evidence on its safety and clinical impact remains limited. Therefore, this study aimed to compare the safety and effectiveness of initiating lecanemab versus AChEIs in patients with mild cognitive impairment (MCI) or AD.  Methods: Using the TriNetX US electronic health record network, we conducted a retrospective cohort study including individuals diagnosed with MCI or AD between July 2023 and September 2025. A target trial emulation with 1:1 propensity score matching and Cox models estimated comparative risks.  Results: Lecanemab was associated with a fivefold higher incidence of neuroimaging abnormalities than AChEIs, while 1-year treatment persistence was similar (53.4% vs 52.5%). After matching, 589 patients were included in each cohort. Compared with AChEIs, lecanemab was associated with significantly lower risks of behavioral and psychological symptoms of dementia (BPSD) (HR, 0.52; 95% CI, 0.36–0.77) and emergency visits (HR, 0.66; 95% CI, 0.51–0.85), but a higher risk of hospitalization (HR, 1.31; 95% CI, 1.03–1.67). Lecanemab was also associated with lower use of antipsychotics (HR, 0.47; 95% CI, 0.32–0.70), antidepressants (HR, 0.60; 95% CI, 0.43–0.85), melatonin/orexin antagonists (HR, 0.61; 95% CI, 0.42–0.88), antibiotics (HR, 0.61; 95% CI, 0.44–0.86), and antifungals (HR, 0.57; 95% CI, 0.37–0.88), whereas steroid use was higher among lecanemab users (HR, 2.19; 95% CI, 1.55–3.10).  Conclusions: Compared with an AChEI-based conventional care strategy, lecanemab initiation was associated with comparable treatment persistence and lower observed risks of BPSD, emergency visit as well as reduced use of psychotropic and infection-related medications in exploratory analyses. However, the higher incidence of neuroimaging abnormalities associated with lecanemab, along with increased risks of hospitalization and corticosteroid use, likely reflects proactive clinical monitoring and management of amyloid-related imaging abnormalities (ARIA). While residual confounding cannot be excluded and results warrant cautious interpretation, these exploratory findings warrant further validation in biomarker-confirmed cohorts and head-to-head randomized trials.  Graphical Abstract:  Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s13195-026-02095-4.
SN  - 1758-9193
ER  -