Would you concur with the rationale of continued long-term lecanemab (intravenous lecanemab) treatment?

Long-Term Lecanemab Treatment: Evidence-Based Recommendation

Based on 48-month efficacy data and FDA labeling, continued long-term lecanemab treatment is supported, with the option to transition to maintenance dosing (every 4 weeks instead of every 2 weeks) after 18 months of treatment. 1

Rationale for Continued Treatment

FDA-Approved Dosing Strategy

• The FDA label explicitly provides for long-term treatment with a transition option: After 18 months of the initial dosing regimen (10 mg/kg every 2 weeks), clinicians may either continue the every-2-week regimen or transition to maintenance dosing of 10 mg/kg every 4 weeks 1
• This regulatory approval inherently supports the concept of continued long-term therapy beyond the initial 18-month period 1

Evidence Against Treatment Discontinuation

• Treatment discontinuation results in loss of clinical benefits: In the phase 2 study (Study 201), when lecanemab was discontinued during a gap period averaging 24 months, the rates of clinical progression in previously treated patients became similar to placebo-treated subjects 2
• The clinical treatment differences achieved during active therapy were maintained during the gap period but did not continue to improve, indicating that ongoing treatment is necessary for continued benefit 2
• Biomarker evidence supports continuous treatment: During treatment gaps, plasma Aβ42/40 ratio and p-tau181 levels began returning toward pre-treatment levels more quickly than amyloid PET changes, suggesting biological disease activity resumes when treatment stops 2

Long-Term Efficacy Data

• Extended treatment maintains clinical benefits: In the open-label extension (OLE) of Study 201, patients who resumed lecanemab after the gap period again demonstrated dose-dependent reductions in amyloid PET, improvements in plasma Aβ42/40 ratio, and reductions in plasma p-tau181 2
• Modeling predicts substantial long-term outcomes: Disease simulation modeling based on trial data predicts that lecanemab treatment extends the mean time to mild, moderate, and severe AD dementia by 2.51,3.13, and 2.34 years respectively, compared to standard of care alone 3
• The model also predicts reduced lifetime probability of institutional care admission (25% vs 31% for standard of care) 3

Quality of Life Considerations

• Patient-reported outcomes favor continued treatment: At 18 months, lecanemab showed 49% less decline in EQ-5D-5L and 56% less decline in QOL-AD scores compared to placebo 4
• Caregiver burden is reduced: The Zarit Burden Interview showed 38% less increase in care partner burden at 18 months with lecanemab treatment 4
• These quality-of-life benefits provide compelling patient-centered justification for long-term therapy 4

Safety Considerations for Long-Term Treatment

ARIA Monitoring Requirements

• ARIA events occur predominantly early in treatment: ARIA-E generally occurred within 3-6 months of treatment initiation in the Clarity AD study 5
• After the initial high-risk period, continued monitoring is still required but the risk profile becomes more favorable 5
• The FDA mandates MRI monitoring prior to the 5th, 7th, and 14th infusions, with additional imaging if symptoms develop 1

Long-Term Safety Profile

• Extended treatment was generally well-tolerated: In the Core + OLE studies involving 1612 participants receiving at least one dose of lecanemab, the most common adverse events were infusion-related reactions (24.5%), ARIA-H microhemorrhages (16.0%), and ARIA-E (13.6%) 5
• ARIA events were largely radiographically mild-to-moderate 5
• Serious safety events remain rare: Among 24 deaths in Core + OLE, only 4 were deemed possibly related to study treatment during the OLE period 5

Clinical Decision Algorithm for Long-Term Treatment

Continue Treatment If:

• Patient demonstrated clinical response or stabilization during initial 18 months 1
• No severe or recurrent ARIA events requiring permanent discontinuation 1
• Patient and caregiver perceive meaningful benefit in cognition, function, or quality of life 4
• No contraindications develop (e.g., need for anticoagulation, recurrent symptomatic ICH) 5

Consider Transition to Maintenance Dosing (Every 4 Weeks) After 18 Months If:

• Patient has achieved substantial amyloid reduction 1
• Clinical stability is maintained 1
• Patient preference favors less frequent infusions 1

Discontinuation May Be Considered Only If:

• Severe ARIA-H (requiring clinical judgment per FDA label) 1
• Intracerebral hemorrhage >1 cm develops 1
• Patient develops contraindications to continued therapy 1
• Patient/caregiver decision after informed discussion of consequences 5

Important Caveats

The evidence strongly suggests that lecanemab's benefits are treatment-dependent rather than representing a permanent disease modification. When treatment is stopped, disease progression resumes at rates similar to untreated patients, though previously achieved improvements may be maintained 2. This pharmacological reality—similar to other chronic disease treatments—supports indefinite continuation rather than time-limited therapy.

ApoE ε4 carrier status affects both efficacy and safety: ApoE ε4 homozygous participants had higher rates of ARIA-E (34.5%) compared to the overall population (13.6%), requiring more intensive monitoring but not necessarily precluding long-term treatment 5.