Treatment-emergent adverse events and laboratory abnormalities up to week 52
| FIL 200 mg+MTX n=416 | FIL 100 mg+MTX n=207 | FIL 200 mg n=210 | MTX n=416 | |
| Safety summary | ||||
| TEAE | 318 (76%) | 164 (79%) | 143 (68%) | 305 (73%) |
| TE SAEs | 26 (6%) | 13 (6%) | 17 (8%) | 28 (7%) |
| TEAE leading to premature discontinuation of study drug | 28 (7%) | 13 (6%) | 5 (2%) | 25 (6%) |
| Death | 3 (1%) | 1 (1%) | 0 | 0 |
| TEAEs in >5% of patients | ||||
| Nausea | 43 (10%) | 32 (16%) | 13 (6%) | 45 (11%) |
| Nasopharyngitis | 16 (4%) | 13 (6%) | 12 (6%) | 16 (4%) |
| Upper respiratory tract infection | 21 (5%) | 5 (2%) | 9 (4%) | 17 (4%) |
| Headache | 18 (4%) | 8 (4%) | 5 (2%) | 19 (5%) |
| Alopaecia | 15 (4%) | 13 (6%) | 3 (1%) | 15 (4%) |
| Diarrhoea | 12 (3%) | 10 (5%) | 4 (2%) | 20 (5%) |
| TEAEs of special interest | ||||
| Infection | 148 (36%) | 76 (37%) | 75 (36%) | 157 (38%) |
| Serious infection | 5 (1%) | 3 (1%) | 5 (2%) | 8 (2%) |
| Opportunistic infection | 1 (<1%)* | 0 | 0 | 2 (1%)† |
| Herpes zoster | 6 (1%) | 3 (1%) | 4 (2%) | 4 (1%) |
| Active TB | 0 | 0 | 0 | 0 |
| Malignancy (excluding NMSC) | 1 (<1%)‡ | 0 | 0 | 4 (1%)§ |
| NMSC | 2 (1%)¶ | 0 | 0 | 1 (<1%)** |
| Gastrointestinal perforations | 1 (<1%)†† | 0 | 0 | 0 |
| Adjudicated VTE | 0 | 0 | 0 | 2 (1%)‡‡ |
| Adjudicated MACE | 4 (1%)§§ | 1 (1%)¶¶ | 2 (1%)*** | 2 (1%)††† |
| Laboratory assessments | ||||
| Haemoglobin change from baseline, mean±SD, g/dL | 0.2±1.2 | 0±1.1 | 0.4±1.1 | −0.1±1.0 |
| G3 or G4 decrease | 6 (2%) | 0 | 1 (1%) | 5 (1%) |
| Neutrophils change from baseline, mean±SD, 103/µL | −1.3±2.1 | −1.3±2.1 | −1.0±2.0 | −0.8±1.8 |
| G3 or G4 decrease | 2 (1%) | 5 (3%) | 2 (1%) | 1 (<1%) |
| Lymphocytes change from baseline, mean±SD, 103/µL | −0.2±0.6 | −0.2±0.7 | −0.1±0.7 | −0.1±0.6 |
| G3 or G4 decrease | 14 (3%) | 3 (2%) | 0 | 6 (2%) |
| Platelets change from baseline, mean±SD, 103/µL | −40±72.6 | −33±66.9 | −50±79.6 | −18±78.2 |
| G3 or G4 decrease | 1 (<1%) | 2 (1%) | 0 | 1 (<1%) |
| ALT change from baseline, mean±SD, 103/µL | 12±29.9 | 6±22.2 | 2±13.0 | 6±19.7 |
| G3 or G4 increase | 18 (4%) | 7 (3%) | 1 (1%) | 4 (1%) |
| AST change from baseline, mean±SD, 103/µL | 9±20.3 | 7±18.4 | 5±9.1 | 4±12.5 |
| G3 or G4 increase | 5 (1%) | 3 (2%) | 2 (1%) | 1 (<1%) |
| Creatinine change from baseline, mean±SD, 103/µL | 0.1±0.1 | 0.04±0.1 | 0.1±0.2 | 0.03±0.1 |
| G3 or G4 increase | 0 | 0 | 0 | 1 (<1%) |
| CK change from baseline, mean±SD, 103/µL | 70±395.1 | 45±79.3 | 73±97.2 | 12±59.7 |
| G3 or G4 increase | 7 (2%) | 3 (2%) | 3 (1%) | 2 (1%) |
| Fasting LDL cholesterol, change from baseline, mean±SD, mg/dL | 17±27.6 | 12±27.8 | 14±28.7 | 2±24.4 |
| % change, mean±SD | 22±32.1 | 16±29.6 | 20±33.5 | 12±23.0 |
| Fasting HDL cholesterol, change from baseline, mean±SD, mg/dL | 11±14.5 | 6±13.6 | 12±15.3 | 1±11.0 |
| % change, mean±SD | 21±30.9 | 12±25.0 | 21±27.9 | 6±23.2 |
| Fasting LDL/HDL ratio, mg/dL, change from baseline, mean±SD, mg/dL | −0.01±0.63 | 0.05±0.62 | −0.1±0.75 | 0.001±0.54 |
Data are shown as n, (%) unless otherwise indicated.
*Oesophageal candida.
†Pneumocystis jirovecii pneumonia and cryptococcal pneumonia.
‡Breast cancer.
§Breast cancer, malignant melanoma, prostate cancer, and small cell lung cancer.
¶Basal cell carcinoma.
**Squamous cell carcinoma.
††Diverticular perforation.
‡‡Two adjudicated events of pulmonary embolism.
§§Two adjudicated events of non-fatal stroke, one adjudicated event each of non-fatal MI and CV death (lupus myocarditis).
¶¶Adjudicated CV death (intracranial aneurysm).
***Adjudicated non-fatal MI and non-fatal stroke.
†††Two adjudicated events of non-fatal stroke.
AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CK, creatine kinase; CV, cardiovascular; FIL, filgotinib; G2, grade 2; G3, grade 3; G4, grade 4; HDL, high-density lipoprotein; LDL, low-density lipoprotein; MACE, major adverse cardiovascular event; MI, myocardial infarction; MTX, methotrexate; NMSC, non-melanoma skin cancer; SAE, serious AE; TB, tuberculosis; TE, treatment-emergent; TEAE, treatment-emergent AE; VTE, venous thromboembolism.