Incidence of Amyloid-Related Imaging Abnormalities in Patients With Alzheimer Disease Treated With Anti-β-Amyloid Immunotherapy: A Meta-analysis

Abstract

Background and objectives: To assess the incidence of amyloid-related imaging abnormalities (ARIA) in clinical trials of anti-β-amyloid (Aβ) immunotherapy and compare the incidence among different agents and clinical characteristics to identify possible predisposing factors for ARIA.

Methods: The PubMed and Embase databases were searched for clinical trials of anti-Aβ immunotherapy published on or before January 12, 2022. Phase 2 or 3 randomized controlled trials reporting detailed data sufficient to assess the incidence of ARIA were selected. The pooled incidences of ARIA and subgroup analyses according to agent and ApoE-4 carrier status were calculated using the DerSimonian-Liard random-effects model. The proportion of symptomatic ARIA cases was also calculated.

Results: In total, 19 eligible studies, including 24 cohorts, were identified and 9,429 patients were analyzed. The overall pooled incidence of ARIA-effusion (E) and ARIA-hemorrhage (H) was 6.5% and 7.8%, respectively. In the subgroup analysis, the incidence of ARIA was different according to the anti-Aβ immunotherapy agent. The cohorts treated with aducanumab had a significantly higher incidence of ARIA-E and ARIA-H (30.7% and 30.0%, respectively; both p < 0.001) compared with cohorts from other drugs. In subgroup analysis according to ApoE-4 carrier status, the incidences of ARIA-E and ARIA-H were higher in the ApoE-4 carrier group than those in the ApoE-4 noncarrier group, but there was no statistical significance (ApoE-4 carrier vs noncarrier, ARIA-E: 8.6% vs 6.9%, p = 0.663, and ARIA-H: 10.5% vs 6.6%, p = 0.398). The pooled proportion of asymptomatic ARIA, detected by routine scheduled MRI surveillances, was 80.4%.

Discussion: The overall incidences of ARIA-E and ARIA-H were 6.5% and 7.8%, respectively, and the pooled proportion of asymptomatic ARIA was 80.4%. The cohorts treated with aducanumab showed a significantly higher incidence of ARIA-E and ARIA-H (30.7% and 30.0%) compared with other drugs.