Introduction: Nocebo effects are unfavourable effects of medications that may be attributed to expectation. Prior to the Phase III trials of nintedanib in patients with ILDs, nintedanib was known to be associated with GI AEs.
Aim: To investigate whether a nocebo effect contributed to GI adverse events reported in the Phase III trials of nintedanib in patients with ILDs.
Methods: We used data from the trials of nintedanib in patients with idiopathic pulmonary fibrosis (INPULSIS), other progressive fibrosing ILDs (INBUILD), and systemic sclerosis-associated ILD (SENSCIS). We analysed the rate of GI AEs in the placebo groups in the on-treatment period (from day of first intake of placebo to last intake plus 7 days) and the post-discontinuation period (from first day after the on-treatment period to end of follow-up), based on time at risk.
Results: Except for nausea in INBUILD, in every trial, the rate of GI AEs in the placebo group fell after placebo was discontinued (Table).
Conclusions: These data suggest that a nocebo effect may have contributed to the GI AEs reported in trials of nintedanib.
Table. Rates of GI adverse events in placebo groups of Phase III trials of nintedanib.
| Period | N | Diarrhoea | Nausea | Vomiting | ||||
| Time at risk (pt-years) |
Rate per 100 pt-years |
Time at risk (pt-years) |
Rate per 100 pt-years |
Time at risk (pt-years) |
Rate per 100 pt-years |
|||
| INPULSIS | On-treatment | 423 | 334.1 | 23.1 | 368.2 | 7.6 | 381.2 | 2.9 |
| Post-discontinuation | 397 | 42.3 | 2.4 | 42.3 | 2.4 | 42.4 | 0 | |
| SENSCIS | On-treatment | 288 | 277.8 | 33.1 | 339.4 | 11.8 | 354.7 | 9.0 |
| Post-discontinuation | 284 | 41.9 | 19.1 | 42.1 | 2.4 | 40.7 | 7.4 | |
| INBUILD | On-treatment | 331 | 364.9 | 23.3 | 429.9 | 7.7 | 450.7 | 3.6 |
| Post-discontinuation | 84 | 44.7 | 2.2 | 42.1 | 9.5 | 45.5 | 0 | |