Lecanemab for AD Shows Sustained Benefit in Real-World Study

LONDON — More than 80% of patients with early Alzheimer’s disease (AD) treated with lecanemab (Leqembi, Eisai/Biogen) in routine practice remained clinically stable or improved over an average of 17 months of treatment, an interim analysis of the real-world LEADER study showed.The real-world safety profile of the antiamyloid therapy was consistent with the drug’s US prescribing information, with most amyloid-related imaging abnormalities (ARIA) being asymptomatic and mild.“These findings demonstrate that the benefits observed in the phase 3 Clarity AD trial are being translated into routine clinical practice across diverse treatment settings,” said lead investigator Babak Tousi, MD, director of the Cleveland Clinic Center for Brain Health in Cleveland.The findings were presented on July 14 at the Alzheimer’s Association International Conference (AAIC) 2026.A Broad Look at Real-World UseThe ongoing LEADER study represents one of the largest real-world assessments of lecanemab since it was approved by the FDA in 2023 and includes patients treated by both dementia specialists and general neurologists in academic and community settings across the US, Tousi noted.The interim analysis included 432 patients with early AD who had received at least seven lecanemab infusions by May 2026. Mean patient age was 74 years, 55.8% were women, 63.9% had mild cognitive impairment (MCI) due to AD, and 36.1% had mild AD dementia at the start of treatment. Mean treatment duration was 520 days, corresponding to roughly 26 doses.Among 427 evaluable patients followed for an average of 17 months, 75.9% remained stable, 6.6% improved from mild AD dementia to MCI due to AD, and 17.6% experienced disease progression based on clinician assessment. The results were consistent across sex, race, ethnicity, and APOE epsilon 4 genotype, Tousi noted.The researchers estimated that 87.8% of patients would remain in the early stages of AD after 30 months of treatment.In analyses by APOE epsilon 4 status, clinician-evaluated stable or improved disease stage was observed in 81.7% of APOE epsilon 4 heterozygotes (stable, 73.8%; improved, 7.9%) and 81.0% of APOE epsilon 4 homozygotes (stable, 75.9%; improved, 5.2%).At the time of chart review, most patients (86.6%) chose to remain on lecanemab treatment, whereas 13.4% had discontinued therapy. Reasons for discontinuation included ARIA, infusion reactions, lack of efficacy, patient preference, logistics, and other adverse events.Among the 155 patients who transitioned to once-monthly intravenous maintenance therapy, 72.3% remained stable and 8.4% improved. Fourteen patients transitioned to once-weekly subcutaneous maintenance therapy, of whom 12 (85.7%) maintained their disease stage.Although the study relied primarily on clinician-assessed disease stage, cognitive measures collected in subsets of patients showed relatively modest changes over follow-up, including mean declines of 1.0 point on the Montreal Cognitive Assessment and 1.6 points on the Mini-Mental State Examination. Functional Assessment Questionnaire scores increased by 2.0 points.The study also highlights how Alzheimer’s diagnostic practices have evolved since lecanemab entered clinical use.At treatment initiation in 2023, amyloid PET imaging accounted for nearly three quarters of diagnostic confirmation, whereas blood-based biomarker (BBM) testing was used in just 12.2% of patients.By 2025, BBM use had more than doubled to 26.5%, reflecting the rapid adoption of blood-based testing in clinical practice, Tousi said. He noted that BBM testing in the US has increased approximately 12-fold since early 2024.Safety Consistent With Clinical Trial Experience Overall ARIA occurred in 12.3% of patients, including ARIA-E in 6.3% and ARIA-H in 7.9%. Most events were asymptomatic and mild in radiographic severity. For comparison, ARIA occurred in 21.3% of patients in the phase 3 Clarity AD trial.Among patients receiving monthly maintenance dosing, no new ARIA-E events, macrohemorrhages, or intracerebral hemorrhages greater than 1 cm were reported. Antithrombotic use was not associated with a meaningful increase in ARIA risk in this cohort, Tousi noted.Positive Safety ProfileCommenting on the findings for Medscape Medical News, Yuko Hara, PhD, director of Aging and Alzheimer’s Prevention at the Alzheimer’s Drug Discovery Foundation, said the 3-year post-approval update provides “the clearest picture yet” of how lecanemab performs outside of a clinical trial.“It is especially encouraging that 87.8% of LEADER patients are estimated to remain in the early stages of Alzheimer’s disease at 30 months of ongoing treatment, meaning many of these patients have been able to maintain their cognitive function and quality of life,” Hara said.Hara added the ARIA findings are “reassuring in that they do not suggest a different real-world safety profile from what clinicians already understand about the treatment. If anything, the ARIA rates appear to be numerically lower in the real-world setting.”Nonetheless, careful patient selection and MRI monitoring “remain essential,” Hara said.Also providing perspective, Rebecca M. Edelmayer, PhD, vice president of Scientific Engagement at the Alzheimer’s Association, said accumulating real-world evidence is “vital” as antiamyloid therapies become more widely used. She said the findings presented at AAIC 2026 reinforce that serious ARIA events remain “rare” and that the side effects of lecanemab and other treatments in its class are “manageable.”Edelmayer also welcomed the increasing adoption of BBMs as “positive news” given that these tests are “much less invasive, less expensive, and may be more convenient for patients than PET scans or spinal fluid analysis.”A separate study reported at AAIC 2026 showed that BBM tests can be useful in primary care, where most patients with cognitive concerns are first evaluated.To guide primary care clinicians in the appropriate use of blood biomarker tests, the Alzheimer’s Association has prepared a concise decision-making tool now available on ALZPro, the organization’s professional resource hub.The LEADER study is sponsored by Eisai. Disclosures for the authors are available with the original presentation materials. Hara and Edelmayer had no relevant disclosures.