Table 3.
Immune-Related Adverse Events.*
| Event | Ipilimumab (N = 471)
|
Placebo (N = 474)
|
||||||
|---|---|---|---|---|---|---|---|---|
| Any Grade | Grade 3 | Grade 4 | Grade 5 | Any Grade | Grade 3 | Grade 4 | Grade 5 | |
| Any immune-related adverse event | 426 (90.4) | 169 (35.9) | 27 (5.7) | 5 (1.1) | 188 (39.7) | 12 (2.5) | 1 (0.2) | 0 |
|
| ||||||||
| Any dermatologic event | 298 (63.3) | 20 (4.2) | 0 | 0 | 99 (20.9) | 0 | 0 | 0 |
| Rash | 161 (34.2) | 5 (1.1) | 0 | 0 | 52 (11.0) | 0 | 0 | 0 |
|
| ||||||||
| Any gastrointestinal event† | 217 (46.1) | 70 (14.9) | 6 (1.3) | 3 (0.6) | 85 (17.9) | 3 (0.6) | 1 (02) | 0 |
| Diarrhea | 194 (41.2) | 46 (9.8) | 0 | 0 | 80 (16.9) | 2 (0.4) | 0 | 0 |
| Colitis | 73 (15.5) | 32 (6.8) | 4 (0.8) | 3 (0.6) | 7 (1.5) | 1 (0.2) | 1 (0.2) | 0 |
|
| ||||||||
| Any endocrine-system event | 178 (37.8) | 34 (7.2) | 3 (0.6) | 0 | 38 (8.0) | 1 (0.2) | 0 | 0 |
| Hypophysitis | 77 (16.3) | 20 (4.2) | 1 (0.2) | 0 | 1 (0.2) | 0 | 0 | 0 |
|
| ||||||||
| Any hepatic event | 115 (24.4) | 38 (8.1) | 13 (2.8) | 0 | 20 (4.2) | 1 (0.2) | 0 | 0 |
| Increase in liver-enzyme levels | 83 (17.6) | 14 (3.0) | 6 (1.3) | 0 | 18 (3.8) | 0 | 0 | 0 |
|
| ||||||||
| Any neurologic event | 21 (4.5) | 5 (1.1) | 4 (0.8) | 0 | 9 (1.9) | 0 | 0 | 0 |
|
| ||||||||
| Other‡ | 111 (23.6) | 34 (7.2) | 2 (0.4) | 2 (0.4) | 23 (4.9) | 8 (1.7) | 0 | 0 |
The safety analysis included all the patients who underwent randomization and received at least one dose of ipilimumab or placebo (945 patients). Immune-related adverse events that occurred in at least 10% of the patients are reported. Patients may have had more than one event. In the ipilimumab group, 5 patients died because of drug-related adverse events; 3 patients died from colitis (2 patients with gastrointestinal perforation), 1 from myocarditis, and 1 from multiorgan failure associated with the Guillain–Barré syndrome.
Gastrointestinal perforation occurred in seven patients (1.5%) in the ipilimumab group (all such events were considered to be related to ipilimumab) and in three patients (0.6%) in the placebo group (none of these events were considered to be related to placebo).
In the ipilimumab group, 26 patients had a grade 3 or 4 lipase level, 4 had a grade 3 or 4 immune-system disorder (hypersensitivity, auto-immune disorder, anaphylactoid reaction, or drug hypersensitivity), 4 had grade 3 lung infiltration, pneumonitis, or interstitial lung disease, 1 had arthritis, and 1 had uveitis.