Table 1.
Clinical characteristics of patients with ICI-related endocrinopathies collected from VigiBase
| ICI (total) | Monotherapy | Combination therapyd | |||||
|---|---|---|---|---|---|---|---|
| Ipilimumab | Nivolumab | Pembrolizumab | Durvalumab | Atezolizumab | |||
| N (%) | 6089 (100.0%) | 1115 (18.3%) | 2449 (40.2%) | 1342 (22.0%) | 111 (1.8%) | 110 (1.8%) | 962 (15.8%) |
| Year | |||||||
| 2011 | 23 (0.4%) | 23 (2.1%) | |||||
| 2012 | 80 (1.3%) | 79 (7.1%) | 1(0.1%) | ||||
| 2013 | 79 (1.3%) | 77 (6.9%) | 2 (0.1%) | ||||
| 2014 | 174 (2.9%) | 166 (14.9%) | 1 (0.0%) | 1 (0.1%) | 1 (0.9%) | 5 (0.5%) | |
| 2015 | 407 (6.7%) | 233 (20.9%) | 39 (1.6%) | 77 (5.7%) | 58 (6.0%) | ||
| 2016 | 676 (11.1%) | 159 (14.3%) | 316 (12.9%) | 92 (6.9%) | 1 (0.9%) | 6 (5.5%) | 102 (10.6%) |
| 2017 | 1595 (26.2%) | 187 (16.8%) | 788 (32.2%) | 289 (21.5%) | 7 (6.3%) | 32 (29.1%) | 292 (30.4%) |
| 2018 | 2612 (42.9%) | 171 (15.3%) | 1100 (44.9%) | 730 (54.4%) | 83 (74.8%) | 64 (58.2%) | 464 (48.2%) |
| 2019e | 443 (7.3%) | 20 (1.8%) | 203 (8.3%) | 153 (11.4%) | 20 (18.0%) | 7 (6.4%) | 40 (4.2%) |
| Gender | |||||||
| Female | 2279/5711 (39.9%) | 395/1030 (38.3%) | 879/2314 (38.0%) | 515/1241 (41.5%) | 34/109 (31.2%) | 41/109 (37.6%) | 415/908 (45.7%) |
| Male | 3432/5711 (60.1%) | 635/1030 (61.7%) | 1435/2314 (62.0%) | 726/1241 (58.5%) | 75/109 (68.8%) | 68/109 (62.4%) | 493/908 (54.3%) |
| Age group | |||||||
| <65 | 2233/4508 (49.5%) | 456/831 (54.9%) | 817/1794 (45.5%) | 429/1015 (42.3%) | 49/84 (58.3%) | 32/82 (39.0%) | 450/702 (64.1%) |
| ≥65 | 2275/4508 (50.5%) | 375/831 (45.1%) | 977/1794 (54.5%) | 586/1025 (57.7%) | 35/84 (41.7%) | 50/82 (61.0%) | 252/702 (35.9%) |
| Region | |||||||
| Americas | 1826 (30.0%) | 584 (9.6%) | 405 (16.5%) | 354 (26.4%) | 25 (22.5%) | 48 (43.6%) | 410 (42.6%) |
| Asia | 1427 (23.4%) | 72 (1.2%) | 734 (30.0%) | 475 (35.4%) | 0 | 8 (7.3%) | 138 (14.3%) |
| Europe | 2665 (43.8%) | 388 (6.4%) | 1289 (52.6%) | 469 (34.9%) | 82 (73.9%) | 52 (47.3%) | 385 (40.0%) |
| Oceania | 170 (2.8%) | 71 (1.2%) | 21 (0.9%) | 44 (3.3%) | 4 (3.6%) | 1 (0.9%) | 29 (3.0%) |
| Africa | 1 (0.0%) | 0 | 0 | 0 | 1 (0.9%) | 0 | |
| Notifiera | |||||||
| Notifier1 | 5220/5906 (88.4%) | 782/1024 (76.4%) | 2262/2427 (93.2%) | 1176/1308 (89.9%) | 104/107 (97.2%) | 99/109 (90.8%) | 797/931 (85.6%) |
| Notifier2 | 686/5906 (11.6%) | 242/1024 (23.6%) | 165/2427 (6.8%) | 132/1308 (10.1%) | 3/107 (2.8%) | 10/109 (9.2%) | 134/931 (14.4%) |
| Indicationb | |||||||
| Malignant melanoma | 2328/5348 (43.5%) | 792/839 (94.4%) | 431/2230 (19.3%) | 401/1195 (33.6%) | 0 | 2/97 (2.1%) | 702/887 (79.1%) |
| Lung cancer | 1912/5348 (35.8%) | 2/839 (0.2%) | 1189/2230 (53.3%) | 532/1195 (44.5%) | 83/100 (83.0%) | 37/97 (38.1%) | 69/887 (7.8%) |
| Renal cell carcinoma | 330/5348 (6.2%) | 1/839 (0.1%) | 284/2230 (12.7%) | 9/1195 (0.8%) | 0 | 7/97 (7.2%) | 29/887 (3.3%) |
| Cancer of head and neck | 83/5348 (1.6%) | 1/839 (0.1%) | 72/2230 (3.2%) | 8/1195 (0.7%) | 2/100 (2.0%) | 0 | 0 |
| Gastric carcinoma | 61/5348 (1.1%) | 0 | 56/2230 (2.5%) | 1/1195 (0.1%) | 0 | 0 | 4/887 (0.5%) |
| Bronchial carcinoma | 49/5348 (0.9%) | 0 | 43/2230 (1.9%) | 5/1195 (0.4%) | 0 | 0 | 1/887 (0.1%) |
| Urothelial carcinoma | 43/5348 (0.8%) | 0 | 6/2230 (0.3%) | 11/1195 (0.9%) | 0 | 26/97 (26.8%) | 0 |
| Others | 542/5348 (10.1%) | 43/839 (5.1%) | 149/2230 (6.7%) | 228/1195 (19.1%) | 15/100 (15.0%) | 25/97 (25.8%) | 82/887 (9.2%) |
| Final outcome | |||||||
| Fatalc | 64/3572 (1.8%) | 17/481 (3.5%) | 21/1520 (1.4%) | 20/862 (2.3%) | 2/72 (2.8%) | 4/564 (0.7%) | |
| Not recovered/not resolved | 1025/3572 (28.7%) | 128/481 (26.6%) | 423/1520 (27.8%) | 281/862 (32.6%) | 23/73 (31.5%) | 31/72 (43.1%) | 139/564 (24.6%) |
| Recovered/resolved | 2483/3572 (69.5%) | 336/481 (69.9%) | 1076/1520 (70.8%) | 561/862 (65.1%) | 50/73 (68.5%) | 39/72 (54.2%) | 421/564 (74.6%) |
Data are described as n (%), n/N (%)
aNotifier1 refers to physician, pharmacist and other health professional. Notifier2 refers to lawyer, consumer
bIndication refers to the primary tumors treated by ICIs, and the complete indications are provided in Attachment 1
cA fatal outcome was defined as causing death; being life-threatening; requiring hospitalization (initial or prolonged); or causing any other medically critical diseases
dCombination therapies include ipilimumab + nivolumab (N = 885), ipilimumab + pembrolizumab (N = 50), ipilimumab + nivolumab + pembrolizumab (N = 27)
eOnly contains cases before March 6, 2019