Validation of 3- and 5-point severity scales to assess ARIA-E.

Abstract

Anti-amyloid-β (Aβ) monoclonal antibodies (mAbs) offer the promise of disease modification and are emerging treatment options in Alzheimer's disease. Anti-Aβ mAbs require brain magnetic resonance imaging (MRI) examinations to detect anti-amyloid-induced amyloid-related imaging abnormalities (ARIA), important adverse drug reactions associated with some anti-Aβ mAbs currently available in the United States and in clinical development. We present a simple rating system for ARIA-edema (ARIA-E) that can assess severity on a 3- or 5-point scale based upon a single linear measurement of the largest area of lesion, and dissemination in space, termed the 3-point Severity Scale of ARIA-E (SSAE-3) and the 5-point Severity Scale of ARIA-E (SSAE-5), respectively. MRI results were collected from 75 participants from the SCarlet RoAD (NCT01224106) and Marguerite RoAD (NCT02051608) studies of gantenerumab. Three neuroradiologists experienced with the detection of ARIA-E were selected to read all cases independently. One rater was then chosen for a second read to assess intra-reader reproducibility. The three raters had high agreement in identifying and grading ARIA-E. The Cohen/Fleiss kappa (κ) scores (95% confidence interval [CI]) for the inter- and intra-reader comparisons for SSAE-3 and SSAE-5 were 0.79 (0.70-1.00), 0.94 (0.94-1.00), 0.73 (0.66-1.00), and 0.90 (0.90-1.00), respectively. Our study suggests that SSAE-3 and SSAE-5 are valid ARIA-E rating scales for use in routine clinical practice by experienced radiologists in specialized settings. The application of these scales in everyday use in clinical practice will support the expansion of anti-Aβ mAbs as a treatment option for people living with Alzheimer's disease. A simple rating scale is needed to rate severity of amyloid-related imaging abnormalities-edema (ARIA-E) in both research and clinical settings.The 3- and 5-point Severity Scales of ARIA-E (SSAE-3/-5) have good inter- and intra-reader agreement.The SSAE-3/-5 have been used in most major Alzheimer's disease (AD) trials to date and are suitable for large-scale use in routine clinical practice, which may help support the expansion of anti-amyloid antibodies as treatment options for AD.