Table 3.
Exposure to study drug and rates of safety events
| PBO-controlled analysis set | Long term, as-treated analysis set | ||||
| FIL 200 mg N=777 |
FIL 100 mg N=788 |
PBO N=781 |
FIL 200 mg N=2267 PYE=4047.7 |
FIL 100 mg N=1647 PYE=2032.9 |
|
| Exposure to study drug, years | |||||
| Mean±SD | 0.4±0.1 | 0.4±0.1 | 0.4±0.1 | 1.8±1.2 | 1.2±0.7 |
| Median (Q1, Q3) | 0.5 (0.5, 0.5) | 0.5 (0.5, 0.5) | 0.5 (0.3, 0.5) | 1.6 (1.0, 2.1) | 1.3 (0.5, 1.8) |
| Cumulative n (%) exposed to study drug | |||||
| Week 12 | 748 (96.3) | 754 (95.7) | 649 (83.1) | 2165 (95.5) | 1547 (93.9) |
| Week 52 | NA | NA | NA | 1731 (76.4) | 1001 (60.8) |
| Week 96 | NA | NA | NA | 799 (35.2) | 360 (21.9) |
| Rates of safety events | EAIR (95% CI) per 100 PYE | EAIR (95% CI) per 100 PYE | |||
| TEAE | 195.4 (173.7 to 219.8) n=354 |
176.3 (156.0 to 199.2) n=323 |
175.9 (155.5 to 198.9) n=316 |
40.4 (38.3 to 42.7) n=1771 |
64.2 (58.9 to 69.9) n=1140 |
| TEAE Grade ≥3 | 12.0 (7.4 to 19.5) n=31 |
11.5 (7.0 to 18.7) n=30 |
10.6 (6.4 to 17.5) n=27 |
6.4 (5.6 to 7.4) n=309 |
7.6 (5.3 to 10.8) n=206 |
| TE SAE | 10.9 (6.7 to 17.8) n=21 |
12.8 (8.1 to 20.4) n=25 |
8.9 (5.2 to 15.2) n=17 |
6.1 (5.4 to 7.0) n=254 |
7.5 (5.6 to 10.1) n=166 |
| TEAE leading to premature discontinuation | 8.7 (4.9 to 15.3) n=15 |
6.3 (3.3 to 12.0) n=11 |
8.8 (5.0 to 15.4) n=15 |
6.0 (5.3 to 6.9) n=239 |
6.8 (5.4 to 8.6) n=93 |
| TEAE leading to temporary interruption | 27.3 (19.7 to 37.8) n=58 |
25.6 (18.3 to 35.6) n=55 |
21.9 (15.4 to 31.1) n=46 |
12.5 (11.3 to 13.8) n=576 |
14.8 (11.9 to 18.5) n=364 |
| All deaths | 0.6 (0.1 to 3.9) n=1 |
0.6 (0.1 to 3.9) n=1 |
0.6 (0.1 to 4.0) n=2 |
0.5 (0.3 to 0.7) n=19 |
0.3 (0.1 to 0.7) n=6 |
| Infectious AEs | 76.9 (63.7 to 92.9) n=139 |
67.3 (55.2 to 82.1) n=123 |
58.0 (47.0 to 71.7) n=104 |
24.8 (23.1 to 26.5) n=1074 |
34.4 (30.4 to 38.8) n=648 |
| Serious infectious AEs | 3.9 (1.6 to 9.1) n=8 |
3.3 (1.4 to 8.2) n=7 |
2.4 (0.9 to 6.7) n=5 |
1.6 (1.2 to 2.1) n=67 |
3.1 (2.1 to 4.5) n=51 |
| Opportunistic infections | 0 | 0 | 0 | 0.1 (0.1 to 0.3) n=5* |
0.2 (0.1 to 0.5) n=4† |
| Active TB | 0 | 0 | 0 | 0 | 0.1 (0.0 to 0.5) n=3 |
| Herpes zoster | 0.6 (0.1 to 3.9) n=1 |
1.1 (0.3 to 4.4) n=2 |
1.1 (0.3 to 4.5) n=2 |
1.8 (1.4 to 2.3) n=74 |
1.1 (0.8 to 1.7) n=23 |
| Herpes simplex virus | 1 (0.1) | 1 (0.1) | 2 (0.3) | 0.6 (0.4 to 1.1) n=33 |
0.9 (0.6 to 1.4) n=18 |
| Adjudicated MACE | 0 | 1.7 (0.3 to 4.8) n=3 |
1.1 (0.1 to 4.0) n=2 |
0.4 (0.2 to 0.7) n=19 |
0.6 (0.4 to 1.1) n=13 |
| CV death | 0 | 0.6 (0.0 to 3.1) n=1 |
0 | 0.1 (0.1 to 0.3) n=6 |
0.2 (0.1 to 0.5) n=4 |
| Nonfatal MI | 0 | 1.1 (0.1 to 4.0) n=2 |
0.6 (0.0 to 3.1) n=1 |
0.1 (0.0 to 0.3) n=4 |
0.2 (0.1 to 0.6) n=5 |
| Nonfatal stroke | 0 | 0 | 0.6 (0.0 to 3.1) n=1 |
0.2 (0.1 to 0.5) n=10 |
0.2 (0.1 to 0.5) n=4 |
| Adjudicated ATE | 0 | 0 | 0 | 0.0 (0.0 to 0.2) n=1 |
0 |
| Adjudicated VTE | 0 | 0 | 0 | 0.2 (0.1 to 0.4) n=8 |
0.0 (0.0 to 0.3) n=1 |
| PE | 0 | 0 | 0 | 0.1 (0.1 to 0.3) n=6 |
0.0 (0.0 to 0.3) n=1 |
| DVT | 0 | 0 | 0 | 0.1 (0.1 to 0.3) n=6 |
0 |
| Malignancy excluding NMSC | 0 | 0.6 (0.0 to 3.1) n=1 |
0.6 (0.0 to 3.1) n=1 |
0.6 (0.4 to 0.9) n=22 |
0.5 (0.3 to 1.0) n=11 |
| NMSC | 0 | 0 | 0 | 0.2 (0.1 to 0.4) n=9 |
0.1 (0.0 to 0.5) n=3 |
| Gastrointestinal perforations | 0 | 0 | 0 | 0.1 (0.0 to 0.2) n=3 |
0 |
The PBO-controlled analysis set only included data up to 12 weeks.
*Two patients reported oesophageal candidiasis, one patient reported pneumonia cryptococcal, one patient reported herpes zoster disseminated and one patient reported both oesophageal candidiasis and pneumonia cryptococcal.
†One patient reported oesophageal candidiasis, one patient reported TB, one patient reported lymph node TB, one patient reported meningitis TB and one patient reported pulmonary TB.
AE, adverse event; ATE, arterial thrombotic event; CV, cardiovascular; DVT, deep vein thrombosis; EAIR, exposure-adjusted incidence rate; FIL, filgotinib; MACE, major adverse cardiovascular event; MI, myocardial infarction; NA, not applicable; NMSC, non-melanoma skin cancer; PBO, placebo; PE, pulmonary embolism; PYE, patient-years exposure; SAE, serious adverse event; TB, tuberculosis; TE, treatment-emergent; TEAE, treatment-emergent adverse event; VTE, venous thromboembolism.