Adverse events over TOMORROW periods 1 and 2 and the open-label extension trial by MedDRA preferred term
| Nintedanib 150 mg twice daily (n=85) | Comparator (n=85) | |
| N (%) | N (%) | |
| Any adverse event(s) | 84 (98.8) | 83 (97.6) |
| Most frequent adverse events* | ||
| Diarrhoea | 63 (74.1) | 34 (40.0) |
| Progression of IPF† | 21 (24.7) | 27 (31.8) |
| Nausea | 23 (27.1) | 18 (21.2) |
| Cough | 14 (16.5) | 24 (28.2) |
| Nasopharyngitis | 14 (16.5) | 18 (21.2) |
| Bronchitis | 13 (15.3) | 19 (22.4) |
| Dyspnoea | 10 (11.8) | 20 (23.5) |
| Vomiting | 16 (18.8) | 11 (12.9) |
| Weight decreased | 15 (17.6) | 11 (12.9) |
| Upper respiratory tract infection | 10 (11.8) | 15 (17.6) |
| Decreased appetite | 14 (16.5) | 6 (7.1) |
| Pneumonia | 4 (4.7) | 13 (15.3) |
| Severe adverse event(s)‡ | 41 (48.2) | 50 (58.8) |
| Serious adverse event(s)§ | 47 (55.3) | 55 (64.7) |
| Fatal adverse event(s) | 12 (14.1) | 31 (36.5) |
| Adverse event(s) leading to treatment discontinuation¶ | 48 (56.5) | 49 (57.6) |
| Diarrhoea | 15 (17.6) | 6 (7.1) |
| Progression of IPF† | 10 (11.8) | 12 (14.1) |
| Nausea | 4 (4.7) | 2 (2.4) |
| Abdominal pain | 3 (3.5) | 0 (0.0) |
| Weight decreased | 3 (3.5) | 1 (1.2) |
| Pneumonia | 0 (0.0) | 4 (4.7) |
Patients in the comparator group received placebo in TOMORROW period 1 and nintedanib 50 mg once daily in period 2. Patients entered the extension trial on the dose that they were receiving at the end of period 2, but had the option to increase dose to nintedanib 150 mg twice daily. Dose reduction from 150 mg twice daily to 100 mg twice daily and treatment interruption were permitted for the management of adverse events.
*Adverse events reported by >15% of patients in either nintedanib 150 mg twice daily or comparator group.
†Corresponds to MedDRA term ‘IPF,’ which included disease worsening and IPF exacerbations.
‡Event that was incapacitating or that caused an inability to work or to perform usual activities.
§Event that resulted in death, was immediately life threatening, resulted in persistent or clinically significant disability or incapacity, required or prolonged hospitalisation, was related to a congenital anomaly or birth defect, or was deemed serious for any other reason.
¶Adverse events leading to treatment discontinuation in >3% of patients in either nintedanib 150 mg twice daily or comparator group. ‘Cardiac disorder adverse events’ (defined according to the MedDRA system organ class) were reported in 19 patients (22.4%) in the nintedanib 150 mg twice daily group and 18 patients (21.2%) in the comparator group.
IPF, idiopathic pulmonary fibrosis; MedDRA, Medical Dictionary for Regulatory Activities.