Table 3.
Safety data to Week 52
| Up to Week 16, n (%) | Up to Week 52, n (%) (EAIR/100 PY) | ||||
| PBO n=281 (PYAR: 87.3) |
BKZ 160 mg every 4 weeks n=431 (PYAR: 134.2) |
Reference arm (ADA 40 mg every 2 weeks) n=140 (PYAR: 43.4) |
BKZ 160 mg every 4 weeks Total n=702* (PYAR: 603.4) |
Reference arm (ADA 40 mg every 2 weeks) n=140 (PYAR: 136.8) |
|
| Any TEAE | 139 (49.5) | 257 (59.6) | 83 (59.3) | 555 (79.1) (222.5) | 113 (80.7) (209.4) |
| Severe TEAEs | 0 | 4 (0.9) | 3 (2.1) | 23 (3.3) | 9 (6.4) |
| Study discontinuation due to TEAEs | 3 (1.1) | 8 (1.9) | 3 (2.1) | 21 (3.0) (3.5) | 7 (5.0) (5.2) |
| Drug-related TEAEs | 35 (12.5) | 100 (23.2) | 34 (24.3) | 224 (31.9) | 54 (38.6) |
| Serious TEAEs | 3 (1.1) | 8 (1.9) | 2 (1.4) | 46 (6.6) (7.9) | 10 (7.1) (7.5) |
| Deaths | 0 | 0 | 0 | 1 (0.1)† | 0 |
| Most frequent adverse events‡ | |||||
| Nasopharyngitis | 13 (4.6) | 40 (9.3) | 7 (5.0) | 84 (12.0) (15.2) | 12 (8.6) (9.4) |
| Upper respiratory tract infection | 18 (6.4) | 22 (5.1) | 3 (2.1) | 50 (7.1) (8.7) | 8 (5.7) (6.1) |
| Urinary tract infection | 4 (1.4) | 9 (2.1) | 3 (2.1) | 43 (6.1) (7.3) | 5 (3.6) (3.7) |
| Headache | 7 (2.5) | 19 (4.4) | 2 (1.4) | 41 (5.8) (7.1) | 6 (4.3) (4.5) |
| Oral candidiasis§ | 0 | 9 (2.1) | 0 | 38 (5.4) (6.5) | 1 (0.7) (0.7) |
| Diarrhoea | 7 (2.5) | 16 (3.7) | 5 (3.6) | 36 (5.1) (6.2) | 7 (5.0) (5.3) |
| Hypertension | 11 (3.9) | 12 (2.8) | 4 (2.9) | 29 (4.1) (4.9) | 9 (6.4) (6.8) |
| ALT elevation | 2 (0.7) | 3 (0.7) | 7 (5.0) | 16 (2.3) (2.7) | 11 (7.9) (8.5) |
| AST elevation | 2 (0.7) | 1 (0.2) | 4 (2.9) | 14 (2.0) (2.3) | 7 (5.0) (5.3) |
| Injection site erythema | 0 | 1 (0.2) | 4 (2.9) | 6 (0.9) (1.0) | 7 (5.0) (5.3) |
| Uveitis | 0 | 0 | 0 | 0 | 0 |
| Adjudicated MACE | 0 | 0 | 0 | 4 (0.6) (0.7)¶ | 0 |
| Neutropenia | 1 (0.4) | 5 (1.2) | 1 (0.7) | 11 (1.6) (1.8) | 2 (1.4) (1.5) |
| Infections | |||||
| Serious | 0 | 1 (0.2) | 1 (0.7) | 6 (0.9) (1.0)** | 2 (1.4) (1.5)** |
| Opportunistic | 0 | 0 | 1 (0.7)†† | 9 (1.3) (1.5) | 1 (0.7) (0.7) |
| Active TB | 0 | 0 | 0 | 0 | 0 |
| Hypersensitivity | 6 (2.1) | 18 (4.2) | 3 (2.1) | 59 (8.4) (10.3) | 7 (5.0) (5.3) |
| Injection site reactions | 3 (1.1) | 5 (1.2) | 7 (5.0) | 15 (2.1) (2.5) | 13 (9.3) (10.2) |
| Adjudicated SIB | 0 | 0 | 0 | 0 | 0 |
| Liver function test changes/enzyme elevations | |||||
| ALT >3×ULN | 0‡‡ | 5 (1.2) | 2 (1.4)§§ | 15 (2.1)§§ | 7 (5.0)§§ |
| AST or ALT >3×ULN | 0‡‡ | 5 (1.2) | 3 (2.2)§§ | 24 (3.4)§§ | 9 (6.5)§§ |
| Adjudicated IBD | 0 | 0 | 0 | 2 (0.3) (0.3)¶¶ | 0 |
| Malignancies excluding non-melanoma skin cancer | |||||
| Breast cancer stage 1 | 1 (0.4) | 0 | 0 | 0 | 0 |
| Colon cancer | 0 | 0 | 0 | 1 (0.1) (0.2) | 0 |
| Chronic lymphocytic leukaemia stage 0 | 0 | 0 | 0 | 1 (0.1) (0.2) | 0 |
| Papillary thyroid cancer | 0 | 0 | 0 | 1 (0.1) (0.2) | 0 |
| Non-melanoma skin cancer | |||||
| Squamous cell carcinoma | 0 | 0 | 0 | 1 (0.1) (0.2) | 0 |
| Basal cell carcinoma | 0 | 1 (0.2) | 0 | 3 (0.4) (0.5) | 0 |
Safety set (Week 16) and active medication set for the overall study period (Week 52). TEAEs are reported for all study groups for Weeks 0–16 and Weeks 0–52. For Weeks 0–52, only TEAEs occurring while receiving BKZ are reported; for patients initially randomised to PBO, only events after switching to BKZ at Week 16 are included.
*Includes patients who switched from PBO to BKZ (events after switch only).
†Motorcycle accident; unrelated to treatment.
‡Most frequent adverse events are those occurring in ≥5% of patients in any study arm.
§All infections were mild or moderate and none were serious, one BKZ-treated patient discontinued.
¶One case each of myocardial infarction, cerebrovascular accident, ischaemic stroke and thrombotic cerebral infarction. The case of ischaemic stroke was deemed by the investigator to be related to study medication.
**Six serious infections were reported on the BKZ treatment arm: one cellulitis, one gangrene, one pneumonia, one upper respiratory tract infection, one cystitis and one urinary tract infection. Two ADA-treated patients reported serious infections: one otitis media and one reported both herpes zoster and atypical pneumonia.
††One opportunistic infection event of herpes zoster was reported for the ADA treatment arm during the double-blind period.
‡‡Data missing for two patients.
§§Data missing for one patient.
¶¶Both ulcerative colitis; one in a patient with a prior history of IBD and the other de novo.
ADA, adalimumab; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BKZ, bimekizumab; EAIR, exposure‑adjusted incident rate; IBD, inflammatory bowel disease; MACE, major adverse cardiovascular event; PBO, placebo; PY, patient‑years; PYAR, patient‑years at risk; SIB, suicidal ideation and behaviour; TB, tuberculosis; TEAE, treatment‑emergent adverse event; ULN, upper limit of normal.