Table 1. Selected Descriptive Characteristics of Amyloid-Related Imaging Abnormalities (ARIA) Magnetic Resonance Imaging (MRI) Findings by Apolipoprotein E (APOE) ε4 Status.
| MRI findings by APOE genotype | No. (%) of participants | |||||
|---|---|---|---|---|---|---|
| Placebo (n = 946) | Gantenerumab (n = 993) | |||||
| APOE ε4 noncarrier (n = 310) | APOE ε4 heterozygous (n = 486) | APOE ε4 homozygous (n = 150) | APOE ε4 noncarrier (n = 335) | APOE ε4 heretozygous (n = 478) | APOE ε4 homozygous (n = 180) | |
| ARIA-E | ||||||
| ARIA-E MRI findings by APOE genotype | ||||||
| Totala | 9 (2.9) | 10 (2.1) | 7 (4.7) | 44 (13.1) | 117 (24.5) | 86 (47.8) |
| No. of episodes | 10 | 11 | 8 | 66 | 170 | 144 |
| Symptomatic ARIA-E | ||||||
| Totalb,a | 1 (0.3) | 1 (0.2) | 0 (0) | 13 (3.9) | 18 (3.8) | 19 (10.6) |
| Those with ARIA-E | 1/9 (11.1) | 1/10 (10.0) | 0/7 (0) | 13/44 (29.5) | 18/117 (15.4) | 19/86 (22.1) |
| Serious symptomatic ARIA-E | ||||||
| Totalb,c | 0 (0) | 0 (0) | 0 (0) | 6 (1.8) | 2 (0.4) | 3 (1.7) |
| Those with ARIA-E | 0/9 (0) | 0/10 (0) | 0/7 (0) | 6/44 (13.6) | 2/117 (1.7) | 3/86 (3.5) |
| ARIA-E with concurrent new ARIA-Hd | ||||||
| Total | 1 (0.3) | 4 (0.8) | 2 (1.3) | 20 (6.0) | 59 (12.3) | 55 (30.6) |
| Those with ARIA-E | 1/9 (11.1) | 4/10 (40.0) | 2/7 (28.6) | 20/44 (45.5) | 59/117 (50.4) | 55/86 (64.0) |
| ARIA-E with concurrent new microhemorrhaged | ||||||
| Total | 1 (0.3) | 2 (0.4) | 0 (0.0) | 17 (5.1) | 43 (9.0) | 50 (27.8) |
| Those with ARIA-E | 1/9 (11.1) | 2/10 (20.0) | 0/7 (0) | 17/44 (38.6) | 43/117 (36.8) | 50/86 (58.1) |
| ARIA-E with concurrent new superficial siderosisd | ||||||
| Total | 1 (0.3) | 2 (0.4) | 2 (1.3) | 14 (4.2) | 38 (7.9) | 25 (13.9) |
| Those with ARIA-E | 1/9 (11.1) | 2/10 (20.0) | 2/7 (28.6) | 14/44 (31.8) | 38/117 (32.5) | 25/86 (29.1) |
| Recurrent ARIA-E | ||||||
| Total | 1 (0.3) | 1 (0.2) | 1 (0.7) | 14 (4.2) | 40 (8.4) | 41 (22.8) |
| Those with ARIA-E at risk of recurrence | 1/6 (16.7) | 1/7 (14.3) | 1/7 (14.3) | 14/30 (46.7) | 40/98 (40.8) | 41/66 (62.1) |
| Time to onset of first ARIA-E, mean (SD), wk | 59.4 (39.7) | 60.9 (34.8) | 49.6 (35.9) | 49.6 (25.6) | 48.8 (20.7) | 45.1 (19.0) |
| Radiological severity of all ARIA-E episodes (BGTS) | ||||||
| Mean (SD) | 3.8 (3.8) | 4.2 (2.9) | 2.9 (2.2) | 8.5 (7.9) | 7.9 (6.1) | 10.5 (8.8) |
| ARIA-E episodes of severity ≥4e | 3/10 (30.0) | 5/11 (45.5) | 3/8 (37.5) | 46/66 (69.7) | 131/170 (77.1) | 116/144 (80.6) |
| Resolution time of all ARIA-E episodes | ||||||
| No. all resolved ARIA-E episodes | 10 | 10 | 8 | 62 | 164 | 139 |
| Mean resolution time (SD), wk | 8.7 (7.1) | 8.8 (4.7) | 4.4 (1.5) | 10.9 (7.3) | 10.3 (8.2) | 13.0 (9.7) |
| Median resolution time, wk | 5.9 | 8.0 | 4.0 | 8.6 | 8.3 | 11.7 |
| ARIA-H | ||||||
| Any new ARIA-H MRI findings by APOE genotype | ||||||
| No. (%) | 31 (10) | 61 (12.6) | 24 (16.0) | 58 (17.3) | 95 (19.9) | 74 (41.1) |
| Mean No. of new findings (SD) | 1.8 (2.8) | 1.7 (1.3) | 1.9 (1.4) | 4.4 (6.8) | 4.3 (5.3) | 9.9 (15.1) |
| Median No. of new findings | 1.0 | 1.0 | 1.0 | 2.0 | 2.0 | 5.0 |
| Any new microhemorrhage | ||||||
| No. (%) | 27 (8.7) | 49 (10.1) | 18 (12.0) | 47 (14.0) | 71 (14.9) | 67 (37.2) |
| Mean No. of new findings (SD) | 1.7 (1.8) | 1.5 (1.0) | 2.0 (1.5) | 3.4 (6.3) | 3.6 (5.0) | 9.3 (15.8) |
| Median No. of new findings | 1.0 | 1.0 | 1.0 | 1.0 | 2.0 | 4.0 |
| Any new superficial siderosis | ||||||
| No. (%) | 5 (1.6) | 16 (3.3) | 8 (5.3) | 25 (7.5) | 54 (11.3) | 37 (20.6) |
| Mean No. of new findings (SD) | 2.2 (2.7) | 1.7 (1.5) | 1.3 (0.5) | 3.8 (4.0) | 2.8 (2.8) | 3.1 (1.9) |
| Median No. of new findings | 1.0 | 1.0 | 1.0 | 2.0 | 2.0 | 3.0 |
Abbreviations: ARIA-E, amyloid-related imaging abnormalities-edema; ARIA-H, amyloid-related imaging abnormalities-hemosiderin; BGTS, Barkhof Grand Total Score.
Reported previously.
Symptomatic ARIA-E was defined as ARIA-E temporally associated with central nervous system symptoms.
Serious symptomatic ARIA-E was defined as ARIA-E associated with central nervous system symptoms where the ARIA-E adverse event and/or the central nervous system symptom adverse event was reported as a serious adverse event.
ARIA-E and ARIA-H concurrence was defined as temporal co-occurrence, with new ARIA-H MRI finding(s) detected at the time of emerging or continuing ARIA-E MRI finding(s).
BGTS 4 or higher was the protocol-mandated threshold for study drug dosing suspension; dosing could continue if ARIA-E event was BGTS less than 4 and asymptomatic.