Nature, incidence and severity of AEs
| Patients, n (%) | Placebo-controlled phase (weeks 0–24*) | Cumulative apremilast exposure† | |
| Placebo n=109 | Apremilast 30 mg twice daily n=109 | Apremilast 30 mg twice daily n=206 | |
| Any AE | 69 (63.3) | 73 (67.0) | 144 (69.9) |
| Any serious AE‡ | 5 (4.6) | 3 (2.8) | 10 (4.9) |
| Any AE leading to study drug withdrawal | 5 (4.6) | 10 (9.2) | 17 (8.3) |
| Any AE leading to death | 0 (0.0) | 0 (0.0) | 1 (0.5) |
| AEs with incidence ≥5% in any treatment group | |||
| Diarrhoea§ | 12 (11.0) | 16 (14.7) | 33 (16.0) |
| Nausea | 2 (1.8) | 9 (8.3) | 16 (7.8) |
| Nasopharyngitis | 7 (6.4) | 9 (8.3) | 16 (7.8) |
| Headache | 4 (3.7) | 8 (7.3) | 12 (5.8) |
| Hypertension | 7 (6.4) | 7 (6.4) | 13 (6.3) |
| Upper respiratory tract infection | 11 (10.1) | 5 (4.6) | 14 (6.8) |
| Select laboratory assessments, n/m (%) | |||
| ALT >3 × ULN, U/L | 1/108 (0.9) | 1/108 (0.9) | 4/205 (2.0) |
| Creatinine >1.7 × ULN, µmol/L | 0/108 (0.0) | 0/108 (0.0) | 1/205 (0.5) |
| Haemoglobin value,<10.5 g/dL (male) or <8.5 g/dL (female) | 2/108 (1.9) | 0/109 (0.0) | 2/205 (1.0) |
| Leucocytes <1.5, 109/L | 0/108 (0.0) | 0/109 (0.0) | 0/205 (0.0) |
| Neutrophils <1.0, 109/L | 1/108 (0.9) | 1/109 (0.9) | 1/205 (0.5) |
| Platelets <75, 109/L | 1/107 (0.9) | 0/109 (0.0) | 0/204 (0.0) |
*Includes the data through week 16 for placebo patients who escaped, and the data through week 24 for all other patients.
†Includes all available apremilast-exposure data up to the data cut of 5 November 2015 (including data beyond 52 weeks); patients with multiple reports are only counted once.
‡During the placebo-controlled phase, serious AEs reported by patients on placebo (n=5) were iron deficiency anaemia, angina pectoris, chest pain, cervical vertebral fracture, spinal column injury, acute myeloid leukaemia and respiratory papilloma; serious AEs reported by patients on apremilast 30 mg twice daily (n=3) were biliary colic, head injury and joint dislocation. New serious AEs of atrial fibrillation, coronary artery disease, alcoholic cardiomyopathy, hypertensive heart disease, cholelithiasis, infective arthritis, bladder transitional cell carcinoma, anxiety, ureteric obstruction and arteriosclerosis were reported by seven patients in the cumulative apremilast-exposure period.
§When using protocol-defined characterisation of diarrhoea of two or more watery or liquid stools/day, incidence rates were 8.3% for placebo and 11.0% for apremilast 30 mg twice daily during the placebo-controlled phase.
AEs, adverse events; ALT, alanine aminotransferase; n/m, number of patients with at least one occurrence of the abnormality/number of patients with at least one post-baseline value; ULN, upper limit of normal.