Table 3.
Overview of adverse events, most commonly reported adverse events and treatment-related serious adverse events
| Patients | Safety analysis population | |
|---|---|---|
| AEs | Events/100 patient-years | |
| n/N (%) | N = 364 | N = 294 patient-years |
| ≥ 1 AE | 145/364 (39.8) | 48.3 (13.3) |
| ≥ 1 treatment-related AE | 102/364 (28.0) | 34.0 (9.3) |
| ≥ 1 treatment-related and at least moderately severe AE | 58/364 (15.9) | 19.3 (5.3) |
| ≥ 1 AE leading to drug withdrawal | 32/364 (8.8) | 10.7 (2.9) |
| ≥ 1 serious AE | 22/364 (6.0) | 7.3 (2.0) |
| ≥ 1 treatment-related serious AEa | 4/364 (1.1) | 1.3 (0.4) |
| Treatment-related serious AEa | Relevant medical history | Outcome |
|---|---|---|
| Completed suicide | Occurred after 5 months of apremilast treatment in a patient who had comorbidities, including alcohol abuse with liver disorder, high blood pressure, chronic obstructive pulmonary disorder, hyperuricaemia, goitre, oedema and gastric reflux. Also, the patient had a prior history of smoking. The patient exhibited no signs of depression either before or during treatment and had a prior family history of two completed suicides (mother and brother) | It could not be determined if there was a causal relationship between the familial suicides and the patient’s completed suicide and if apremilast treatment increased the risk of suicide. Because the relationship of this serious AE with apremilast could not be excluded or proven by the study investigator, the causality was classified as possibly treatment related |
| Bronchitis | Patient had a diagnosis of a chronic lung disorder prior to the start of apremilast treatment, as well as comorbid high blood pressure and hypothyroidism | Apremilast treatment was permanently discontinued, and the patient recovered from bronchitis |
| Weight loss | Patient who lost 9 kg after 5 months of apremilast treatment had comorbid hypertension, type 1 diabetes mellitus, diarrhoea, dyslipidaemia and hyperthyroidism | Apremilast treatment was temporarily interrupted in this patient in accordance with the apremilast Summary of Product Characteristics |
| Seizure (including racing heart and tremor) | Occurred after 2 months of apremilast treatment in a patient who had comorbid high blood pressure, hypercholesterolaemia, kidney failure, type 2 diabetes, heart failure and aortic stenosis | Apremilast was permanently discontinued, and the patient recovered from this AE |
| AEs in ≥ 5% of patients in clinical trials of apremilast1,2 n/N (%)b |
LAPIS-PSO safety analysis population | |
|---|---|---|
| Most frequent AEs |
Events per 100 patient-years | |
| N = 364 | N = 294 patient-years | |
| Diarrhoea | 33/364 (9.1) | 11.0 (3.0) |
| Headachec | 23/364 (6.3) | 7.7 (2.1) |
| Nausea | 18/364 (4.9) | 6.0 (1.6) |
| URTId | 2/364 (0.5) | 1.3 (0.4) |
| Median time to first occurrencee | N | Median time, days |
|---|---|---|
| Diarrhoea | 32 | 7.0 |
| Headache | 23 | 9.0 |
| Nausea | 18 | 5.5 |
| URTI | 3 | 13.0 |
AE adverse event, URTI upper respiratory tract infection
aCausality suspected or cannot be excluded according to investigator
bAEs with a causal relationship to apremilast treatment
cTension headache was reported in one patient (0.3%)
dTreatment-related nasopharyngitis was reported in two patients (0.5%)
eAEs with or without a causal relationship to apremilast treatment. AEs with a start date before baseline were excluded from this analysis