Table 2.
Frequency of adverse events, serious adverse events, and treatment discontinuations (safety cohort N = 83 803)
| No. of patients, n (%) | All-causality | Treatment-related |
|---|---|---|
| No. of AEsa | 23 163 | 3108 |
| Patients with AEs | 12 055 (14.4) | 2638 (3.1) |
| Patients with dose reduction due to AEs | 180 (0.2) | 134 (0.2) |
| Patients with drug discontinuationb due to AEs | 1349 (1.6) | 504 (0.6) |
| AEs in ≥ 0.2% patients | ||
| Headache | 987 (1.2) | 328 (0.4) |
| Scoliosis | 514 (0.6) | 162 (0.2) |
| Upper respiratory tract infection | 474 (0.6) | 4 (0.0) |
| Arthralgia | 431 (0.5) | 129 (0.2) |
| Pyrexia | 425 (0.5) | 13 (0.0) |
| Ear infection | 408 (0.5) | 3 (0.0) |
| Influenza | 404 (0.5) | 4 (0.0) |
| Nasopharyngitis | 391 (0.5) | 5 (0.0) |
| Gastroenteritis | 273 (0.3) | 3 (0.0) |
| Tonsillitis | 244 (0.3) | 7 (0.0) |
| Abdominal pain | 228 (0.3) | 11 (0.0) |
| Varicella | 223 (0.3) | 1 (0.0) |
| Vomiting | 211 (0.3) | 22 (0.0) |
| Pain in extremity | 207 (0.2) | 67 (0.1) |
| Asthma | 207 (0.2) | 3 (0.0) |
| Elevated IGF-1c | 188 (0.2) | 146 (0.2) |
| Cough | 187 (0.2) | 6 (0.0) |
| Fatigue | 181 (0.2) | 30 (0.0) |
| Pneumonia | 181 (0.2) | 0 (0.0) |
| Craniopharyngioma | 170 (0.2) | 47 (0.1) |
| Otitis media | 170 (0.2) | 1 (0.0) |
| Bronchitis | 169 (0.2) | 2 (0.0) |
| Convulsion | 166 (0.2) | 16 (0.0) |
| Epilepsy | 152 (0.2) | 14 (0.0) |
| Back pain | 151 (0.2) | 24 (0.0) |
| Melanocytic nevus | 147 (0.2) | 62 (0.1) |
| Urinary tract infection | 143 (0.2) | 4 (0.0) |
| Diarrhea | 140 (0.2) | 3 (0.0) |
| Viral infection | 137 (0.2) | 2 (0.0) |
| Other AEs of interest | ||
| Neoplasm recurrence | 105 (0.1) | 23 (0.0) |
| Recurrent cancer | 91 (0.1) | 25 (0.0) |
| Benign intracranial hypertension | 54 (0.1) | 49 (0.1) |
| Epiphysiolysis | 80 (0.1) | 48 (0.1) |
| Cerebral hemorrhage | 7 (0.0) | 1 (0.0) |
| Hemorrhage intracranial | 3 (0.0) | 2 (0.0) |
| Intraventricular hemorrhage | 1 (0.0) | 0 |
| Subarachnoid hemorrhage | 1 (0.0) | 0 |
| Bone giant cell tumor | 1 (0.0) | 0 |
| Bone neoplasm | 3 (0.0) | 0 |
| Bone sarcoma | 4 (0.0) | 1 (0.0) |
| Ewing sarcoma | 1 (0.0) | 1 (0.0) |
| Ewing sarcoma recurrent | 1 (0.0) | 1 (0.0) |
| Osteochondroma | 10 (0.0) | 2 (0.0) |
| Osteoma | 2 (0.0) | 2 (0.0) |
| Enchondroma | 1 (0.0) | 0 |
| Enchondromatosis | 1 (0.0) | 1 (0.0) |
| Diabetes mellitus | 37 (0.0) | 19 (0.0) |
| Type 1 diabetes mellitus | 35 (0.0) | 15 (0.0) |
| Type 2 diabetes mellitus | 21 (0.0) | 12 (0.0) |
| Insulin-resistant diabetes | 2 (0.0) | 1 (0.0) |
| Diabetes mellitus malnutrition-related | 1 (0.0) | 0 |
| No. of SAEsa | 3981 | 657 |
| Patients with SAEs | 3108 (3.7) | 607 (0.7) |
| Patients with drug discontinuationb due to SAEs | 1030 (1.2) | 345 (0.4) |
| SAEs in ≥ 0.1% patients | ||
| Craniopharyngiomad | 151 (0.2) | 42 (0.1) |
| Neoplasm recurrence | 99 (0.1) | 23 (0.0) |
| Scoliosis | 91 (0.1) | 43 (0.1) |
| Recurrent cancer | 91 (0.1) | 26 (0.0) |
| Epiphysiolysis | 61 (0.1) | 38 (0.0) |
| Convulsion | 60 (0.1) | 6 (0.0) |
| Death | 59 (0.1) | 5 (0.0) |
| Vomiting | 47 (0.1) | 3 (0.0) |
| Pneumonia | 47 (0.1) | 0 (0.0) |
| Headache | 45 (0.1) | 11 (0.0) |
| Epilepsy | 43 (0.1) | 4 (0.0) |
| Appendicitis | 42 (0.1) | 1 (0.0) |
Abbreviations: AE, adverse event; IGF-1, insulin-like growth factor-1; MedDRA, Medical Dictionary for Regulatory Activities; SAE, serious adverse event.
a
Multiple AEs/SAEs reported under the same MedDRA preferred term were counted once for the same patient.
b
Temporary, permanent, or delayed drug discontinuation.
c
Elevated IGF-1: outside the normal range defined by the laboratory used for the test.
d
These are craniopharyngioma recurrences rather than de novo cases.