Table 3.
Adverse events and laboratory abnormalities during the placebo‐controlled phase (Weeks 0 to 16) and the apremilast‐extension phase (Weeks 16 to 52) (Safety population, N = 250)
| Placebo‐controlled phase: Weeks 0 to 16 | Apremilast‐extension phase: Weeks 16 to 52 | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overview, patients, n (%) | Placebo n = 84 | EAIR/100 Pt‐Yrs | Apremilast n = 83 | EAIR/100 Pt‐Yrs | Etanercept n = 83 | EAIR/100 Pt‐Yrs | Placebo/Apremilastb n = 73 | EAIR/100 Pt‐Yrs | Apremilast/Apremilast n = 74 | EAIR/100 Pt‐Yrs | Etanercept/Apremilastc n = 79 | EAIR/100 Pt‐Yrs |
| ≥1 AE | 45 (53.6) | 292.0 | 59 (71.1) | 469.0 | 44 (53.0) | 288.8 | 41 (56.2) | 170.0 | 44 (59.5) | 184.9 | 49 (62.0) | 167.1 |
| ≥1 severe AE | 2 (2.4) | 8.4 | 3 (3.6) | 12.6 | 3 (3.6) | 12.0 | 3 (4.1) | 6.9 | 3 (4.1) | 6.7 | 4 (5.1) | 8.3 |
| ≥1 serious AE | 0 (0.0) | 0.0 | 3 (3.6) | 12.6 | 2 (2.4) | 7.9 | 4 (5.5) | 9.2 | 2 (2.7) | 4.5 | 2 (2.5) | 4.1 |
| ≥1 AE leading to drug withdrawal | 2 (2.4) | 8.3 | 3 (3.6) | 12.5 | 2 (2.4) | 7.9 | 3 (4.1) | 6.8 | 3 (4.1) | 6.7 | 2 (2.5) | 4.1 |
| Reported by ≥5% of patients in any treatment group, n (%) | ||||||||||||
| Diarrhoea | 3 (3.6) | 12.9 | 9 (10.8) | 41.5 | 1 (1.2) | 4.0 | 13 (17.8) | 33.9 | 4 (5.4) | 9.3 | 6 (7.6) | 13.0 |
| Nausea | 1 (1.2) | 4.2 | 9 (10.8) | 40.9 | 4 (4.8) | 16.4 | 4 (5.5) | 9.3 | 3 (4.1) | 6.8 | 5 (6.3) | 10.8 |
| Upper respiratory tract infection | 2 (2.4) | 8.5 | 6 (7.2) | 25.9 | 2 (2.4) | 8.1 | 3 (4.1) | 6.9 | 4 (5.4) | 9.3 | 1 (1.3) | 2.1 |
| Nasopharyngitis | 8 (9.5) | 34.8 | 4 (4.8) | 17.0 | 8 (9.6) | 33.4 | 3 (4.1) | 7.0 | 2 (2.7) | 4.5 | 4 (5.1) | 8.5 |
| Headache | 3 (3.6) | 12.8 | 11 (13.3) | 51.6 | 5 (6.0) | 20.8 | 4 (5.5) | 9.4 | 2 (2.7) | 4.5 | 2 (2.5) | 4.2 |
| Tension headache | 4 (4.8) | 17.2 | 5 (6.0) | 21.8 | 3 (3.6) | 12.1 | 3 (4.1) | 7.0 | 0 (0.0) | 0.0 | 1 (1.3) | 2.1 |
| Sinusitis | 0 (0.0) | 0.0 | 0 (0.0) | 0.0 | 0 (0.0) | 0.0 | 0 (0.0) | 0.0 | 1 (1.4) | 2.2 | 4 (5.1) | 8.3 |
| Select marked laboratory abnormalities, a n/m (%) | ||||||||||||
| ALT >3 × ULN, U/L | 1/83 (1.2) | 4.2 | 1/83 (1.2) | 4.2 | 0/83 (0.0) | 0.0 | 0/72 (0.0) | 0.0 | 0/74 (0.0) | 0.0 | 1/78 (1.3) | 2.1 |
| AST >3 × ULN, U/L | 0/83 (0.0) | 0.0 | 1/83 (1.2) | 4.2 | 0/83 (0.0) | 0.0 | 0/72 (0.0) | 0.0 | 0/74 (0.0) | 0.0 | 1/78 (1.3) | 2.1 |
| Total bilirubin >1.8 × ULN, μmol/L | 1/83 (1.2) | 4.2 | 1/83 (1.2) | 4.2 | 0/83 (0.0) | 0.0 | 1/72 (1.4) | 2.3 | 0/74 (0.0) | 0.0 | 1/78 (1.3) | 2.1 |
| Haemoglobin A1C >9% | 1/81 (1.2) | 4.3 | 0/79 (0.0) | 0.0 | 0/81 (0.0) | 0.0 | 1/72 (1.4) | 2.3 | 0/70 (0.0) | 0.0 | 0/74 (0.0) | 0.0 |
| Total cholesterol >7.8 mmol/L | 4/83 (4.8) | 17.2 | 3/83 (3.6) | 12.7 | 2/83 (2.4) | 8.0 | 2/72 (2.8) | 4.6 | 5/74 (6.8) | 11.6 | 1/78 (1.3) | 2.1 |
| Triglycerides >3.4 mmol/L | 18/83 (21.7) | 84.2 | 10/83 (12.0) | 44.6 | 14/83 (16.9) | 61.0 | 8/72 (11.1) | 20.1 | 11/74 (14.9) | 27.3 | 14/78 (17.9) | 33.5 |
| Lymphocytes <0.8 × 109/L | 2/83 (2.4) | 8.4 | 3/83 (3.6) | 12.7 | 0/83 (0.0) | 0.0 | 1/72 (1.4) | 2.3 | 1/74 (1.4) | 2.2 | 2/77 (2.6) | 4.2 |
| Neutrophils <1 × 109/L | 0/83 (0.0) | 0.0 | 0/83 (0.0) | 0.0 | 1/83 (1.2) | 4.0 | 0/72 (0.0) | 0.0 | 0/74 (0.0) | 0.0 | 0/77 (0.0) | 0.0 |
Exposure‐adjusted incidence rate (EAIR) per 100 patient‐years is defined as 100 times the number (n) of patients reporting the event divided by patient‐years within the phase (up to the first event start date for patients reporting the event). The n/m represents patients with ≥1 occurrence of the abnormality (n)/patients with ≥1 post‐baseline value (m).
All laboratory measurements are non‐fasting values.
No dose titration for apremilast.
Dose titration for apremilast.
ALT, alanine aminotransferase; AST, aspartate aminotransferase; Pt‐Yrs, patient‐years; ULN, upper limit of normal.