Table 3. Summary of Adverse Events (AEs) by Treatment Group.
| Event | Donanemab (n = 853)a | Placebo (n = 874)a |
|---|---|---|
| Overview of AEs, No. (%) | ||
| Deathb | 16 (1.9)c | 10 (1.1) |
| Death considered related to treatmentd | 3 (0.4) | 1 (0.1) |
| Participants with ≥1 serious AEe | 148 (17.4) | 138 (15.8) |
| Treatment discontinuations due to AEs | 112 (13.1) | 38 (4.3) |
| Study discontinuations due to AEs | 69 (8.1) | 32 (3.7) |
| Participants with ≥1 treatment-emergent AEf | 759 (89.0) | 718 (82.2) |
| Treatment-emergent AEs ≥5% incidence, No. (%) | ||
| ARIA-E | 205 (24.0) | 17 (1.9) |
| ARIA-H | 168 (19.7) | 65 (7.4) |
| COVID-19 | 136 (15.9) | 154 (17.6) |
| Headache | 119 (14.0) | 86 (9.8) |
| Fall | 114 (13.4) | 110 (12.6) |
| Infusion-related reaction | 74 (8.7) | 4 (0.5) |
| Superficial siderosis of central nervous system | 58 (6.8) | 10 (1.1) |
| Dizziness | 53 (6.2) | 48 (5.5) |
| Arthralgia | 49 (5.7) | 42 (4.8) |
| Urinary tract infection | 45 (5.3) | 59 (6.8) |
| Diarrhea | 43 (5.0) | 50 (5.7) |
| Fatigue | 42 (4.9) | 45 (5.1) |
| Overview of ARIAg | ||
| Microhemorrhage or superficial siderosis present at baseline, No. (%) | 124 (14.5) | 161 (18.4) |
| ARIA-E by APOE ε4 allele status, No./total No. (%) | ||
| Noncarrier | 40/255 (15.7) | 2/250 (0.8) |
| Heterozygous carrier | 103/452 (22.8) | 9/474 (1.9) |
| Homozygous carrier | 58/143 (40.6) | 5/146 (3.4) |
| Any ARIA, No. (%)h | 314 (36.8) | 130 (14.9) |
| ARIA-E, No. (%) | 205 (24.0) | 18 (2.1) |
| Asymptomatic | 153 (17.9) | 17 (1.9) |
| Symptomatic | 52 (6.1) | 1 (0.1)i |
| ARIA-H, No. (%) | 268 (31.4) | 119 (13.6) |
| Microhemorrhage | 229 (26.8) | 109 (12.5) |
| Superficial siderosis | 134 (15.7) | 26 (3.0) |
| Intracerebral hemorrhage >1 cm | 3 (0.4) | 2 (0.2) |
Abbreviations: APOE, apolipoprotein E; ARIA-E, amyloid-related imaging abnormalities of edema/effusions; ARIA-H, amyloid-related imaging abnormality of microhemorrhages and hemosiderin deposits; MRI, magnetic resonance imaging.
Participants may have been counted in more than 1 category; adverse events population is defined as all participants that received at least 1 infusion.
Deaths are also included under serious AEs and discontinuations due to AEs.
Includes 1 death that occurred after treatment completion and in the follow-up period.
Deaths related to donanemab occurred subsequent to ARIA and the death related to placebo occurred due to arteriosclerosis.
Definition of serious AE: results in death, is life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, or based on other medical/scientific judgment.
Definition of treatment-emergent adverse event: an untoward medical occurrence that emerges during a defined treatment period, having been absent pretreatment, or worsens relative to the pretreatment state, and does not necessarily have to have a causal relationship with this treatment.
Based on safety MRI or treatment-emergent AE cluster (after baseline); APOE4 is a known risk factor for ARIA-E.30
Based on MRI.
One placebo-treated participant had ARIA-E during the placebo-controlled period; however, the participant developed symptoms during the long-term extension period.