Zorginstituut Nederland’s Lecanemab Health Insurance Rejection: Implications for Alzheimer’s Care
Dutch Health Insurance Rejects Lecanemab Coverage
Zorginstituut Nederland’s advisory letter dated 13 February 2026 recommends against including lecanemab (Leqembi®) in the Dutch basic health insurance package, marking a key lecanemab health insurance rejection for adults with mild cognitive impairment (MCI) or mild dementia due to early Alzheimer’s disease who are apolipoprotein E ε4 (ApoE ε4) non-carriers or heterozygotes with confirmed amyloid pathology. The assessment, informed by a pharmacotherapeutic report finalized 22 January 2025, concludes that lecanemab fails the legal criterion of “stand van de wetenschap en praktijk” (state of science and practice), primarily due to lack of clinically relevant benefits over best supportive care despite statistically significant effects in the Clarity AD phase III randomized controlled trial (RCT). This decision halts further evaluation under the four standard package criteria—effectiveness, cost-effectiveness, necessity, and feasibility—prioritizing evidence-based added value for jointly funded care, as detailed in Zorginstituut Nederland’s announcement.
Clinical Benefits Fall Short of Relevance Thresholds
The Clarity AD RCT (n=1,795 total; subgroup n=1,466 for ApoE ε4 non-carriers/heterozygotes) compared lecanemab (10 mg/kg IV every two weeks) plus best supportive care to placebo plus best supportive care over 18 months, with key outcomes measured via validated scales including Clinical Dementia Rating-Sum of Boxes (CDR-SB), Alzheimer’s Disease Assessment Scale-Cognitive subscale version 14 (ADAS-Cog14), and Alzheimer’s Disease Cooperative Study-Activities of Daily Living for Mild Cognitive Impairment (ADCS-MCI-ADL). On CDR-SB (range 0-18; higher scores indicate greater impairment; minimal important difference [MID] ≥1 for MCI, ≥2 for mild dementia), lecanemab showed a mean difference of 0.58 points less decline (95% CI 0.35-0.81; p<0.001), statistically significant but below MID thresholds, indicating no clinically meaningful slowing of cognitive decline. Similarly, ADAS-Cog14 (range 0-90; MID ≥4) yielded 1.51 points less decline (95% CI 0.54-2.49), and ADCS-MCI-ADL (range 0-53; MID ≥3.7) showed 1.94 points less decline (95% CI 1.03-2.84), both statistically significant yet clinically irrelevant per literature-derived MIDs and GRADE-assessed moderate evidence quality. Amyloid plaque clearance correlated poorly with these outcomes, undermining surrogate claims, while quality-of-life data (QoL-AD) lacked subgroup publication, precluding firm conclusions.
Evidence Graded Under Strict PICO Framework
Zorginstituut Nederland evaluated lecanemab against best supportive care—encompassing individualized care plans, non-pharmacological interventions, and limited symptomatic treatments like cholinesterase inhibitors (used in ~21% of Dutch early Alzheimer’s patients versus ~58% in Clarity AD)—using a systematic literature review (August 2025; PubMed/Cochrane; two publications included) focused on RCTs per PICO criteria: early Alzheimer’s patients (MCI/mild dementia, amyloid-positive, ApoE ε4 non-carriers/heterozygotes), intervention (lecanemab + supportive care), comparator (supportive care), and outcomes (cognition, daily function, quality of life, serious adverse events [SAEs]). The Clarity AD trial stratified randomization by clinical subgroup, symptomatic medication use, ApoE ε4 status, and region, powering for CDR-SB differences with 90% power assuming 20% dropout; post-hoc subgroup analyses (84.7% of population) were supported by total-population data due to consistency. Risks of bias (attrition ~15%, potential unblinding from ARIA events) were downgraded per GRADE, yielding moderate evidence for primary outcomes. Dutch professional societies (e.g., NVN, NHG) expressed no consensus or support for adoption, citing negligible clinical relevance.
Safety Risks and Feasibility Block Reimbursement Path
This lecanemab health insurance rejection highlights challenges in Alzheimer’s reimbursement, where small effect sizes fail to meet clinical relevance thresholds despite EMA conditional approval (15 April 2025) based on a favorable benefit-risk in the subgroup, driven by reduced amyloid-related imaging abnormalities (ARIA). Lecanemab elevates SAEs (14.0% vs. 11.3%; RR 1.25, 95% CI 0.98-1.59; low GRADE evidence) and discontinuations due to adverse events (6.9% vs. 2.9%; RR 2.38, 95% CI 1.52-3.73; moderate evidence), including symptomatic ARIA-E (2% vs. 0%) and ARIA-H (0.8% vs. 0.1%), with macro-hemorrhages in 0.5%. Infrastructure demands (IV infusion biweekly, serial MRIs, amyloid-PET/lumbar puncture, ApoE genotyping) strain feasibility, potentially excluding ~85-92% of ~76,000 prevalent early Alzheimer’s cases in the Netherlands. Implications extend to market access for amyloid-targeting therapies, prioritizing demonstrated progression delays over statistical signals amid rising prevalence (projected doubling by 2050); this aligns with cautious HTA precedents, reinforcing cost-containment via stringent “stand van de wetenschap en praktijk” until long-term data (e.g., 36-month extensions showing no CDR-SB MID attainment) substantiate value.
