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

Abstract

ObjectivesTo assess the incidence of ARIA in clinical trials of anti-Aβ immunotherapy and compare the incidence among different agents and clinical characteristics to identify possible predisposing factors for ARIA.MethodsThe 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.ResultsIn 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 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 to 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 ApoE-4 non-carrier group, but there was no statistical significance ( ApoE-4 carrier vs. non-carrier, 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%.ConclusionsThe 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.