Summary of absolute numbers and proportions of patients in each treatment group who experienced TEAEs and laboratory abnormalities over the course of the study
| Continued once-daily groups | Continued twice-daily groups | Non-responders* switching to 100 mg/day | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Patients with | Continued placebo (N=56) | 50 mg (N=63) | 100 mg (N=85) | 200 mg (N=86) | 2×25 mg (N=69) | 2×50 mg (N=85) | 2×100 mg (N=84) | Placebo to 100 mg (N=15) | Placebo to 2×50 mg (N=15) | 50–100 mg (N=19) | 2×25 mg to 2×50 mg (N=17) |
| TEAE, n (%) | 32 (57.1) | 33 (52.4) | 37 (43.5) | 50 (58.1) | 37 (53.6) | 46 (54.1) | 45 (53.6) | 7 (46.7) | 7 (46.7) | 9 (47.4) | 12 (70.6) |
| Serious TEAE, n (%) | 4 (7.1) | 0 (0) | 4 (4.7) | 2 (2.3) | 1 (1.4) | 0 (0) | 3 (3.6) | 0 (0) | 0 (0) | 0 (0) | 1 (5.9) |
| SAE leading to death, n (%) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 1 (1.2) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Serious TE infection, n (%) | 1 (1.8)† | 0 (0) | 3 (3.5)‡ | 1 (1.2)§ | 0 (0) | 0 (0) | 1 (1.2)¶ | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Related TEAE, n (%) | 6 (10.7) | 13 (20.6) | 11 (12.9) | 21 (24.4) | 14 (20.3) | 19 (22.4) | 21 (25.0) | 2 (13.3) | 0 (0) | 2 (10.5) | 2 (11.8) |
| Related TEAE infection, n (%) | 1 (1.8) | 4 (6.3) | 4 (4.7) | 7 (8.1) | 5 (7.2) | 7 (8.2) | 7 (8.3) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Herpes zoster infection | 1 | 0 | 0 | 1 | 1 | 0 | 2 | 0 | 0 | 0 | 0 |
| TEAE leading to permanent discontinuation of study treatment, n (%) | 2 (3.6) | 2 (3.2) | 5 (5.9)** | 3 (3.5) | 5 (7.2) | 2 (2.4) | 3 (3.6) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| TE laboratory abnormalities, n (%) | |||||||||||
| Decreased haemoglobin, g/dL | |||||||||||
| Grade 1 (10, LLN) | 11 (19.36) | 13 (20.6) | 10 (11.8) | 11 (12.8) | 11 (15.9) | 13 (15.3) | 13 (15.5) | 6 (40.0) | 4 (26.7) | 3 (15.8) | 4 (23.5) |
| Grade 2 (<10–8) | 4 (7.1) | 2 (3.2) | 7 (8.3) | 2 (2.3) | 2 (2.3) | 4 (4.7) | 1 (1.2) | 0 (0) | 0 (0) | 2 (10.5) | 1 (5.9) |
| Grade 3 (<8.0–6.5) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 1 (1.2) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Grade 4 (<6.5) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Decreased lymphocytes, ×109/L | |||||||||||
| Grade 1 (0.8, LLN) | 1 (1.8) | 2 (3.2) | 0 (0) | 3 (3.5) | 3 (4.3) | 1 (1.2) | 2 (2.4) | 0 (0) | 1 (6.7) | 1 (5.3) | 0 (0) |
| Grade 2 (<0.8–0.5) | 3 (5.4) | 6 (9.5) | 4 (4.7) | 5 (5.8) | 2 (2.9) | 4 (4.7) | 4 (4.87) | 0 (0) | 0 (0) | 1 (5.3) | 3 (17.6) |
| Grade 3 (<0.5–0.2) | 1 (1.8) | 1 (1.6) | 2 (2.4) | 0 (0) | 1 (1.4) | 1 (1.2) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 1 (5.9) |
| Grade 4 (<0.2) | 0 (0) | 0 (0) | 1 (1.2) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Decreased neutrophils, ×109/L | |||||||||||
| Grade 1 (1.5, LLN) | 1 (1.8) | 1 (1.6) | 1 (1.2) | 4 (4.7) | 3 (4.3) | 1 (1.2) | 1 (1.2) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Grade 2 (<1.5–1.0) | 3 (5.4) | 0 (0) | 0 (0) | 3 (3.5) | 2 (2.9) | 1 (1.2) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Grade 3 (<1.0–0.5) | 0 (0) | 0 (0) | 0 (0) | 1 (1.2) | 0 (0) | 0 (0) | 0 (0) | 1 (6.7) | 0 (0) | 0 (0) | 0 (0) |
| Grade 4 (<0.5) | 0 (0) | 0 (0) | 1 (1.2) | 0 (0) | 0 (0) | 0 (0) | 1 (1.2) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Decreased platelets, ×109/L | |||||||||||
| Grade 1 (75, LLN) | 1 (1.8) | 0 (0) | 2 (2.4) | 3 (3.5) | 0 (0) | 1 (1.2) | 2 (2.4) | 0 (0) | 0 (0) | 1 (5.3) | 0 (0) |
| Grade 2 (<75–50) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Grade 3 (<50–25) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Grade 4 (<25) | 0 (0) | 0 (0) | 1 (1.2) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| NK cells (CD16CD56), ×109/L | |||||||||||
| Decrease to <LLN | 3 (5.4) | 5 (7.9) | 5 (5.9) | 12 (14.0) | 7 (10.1) | 5 (5.9) | 6 (7.1) | 2 (13.3) | 2 (13.3) | 0 (0) | 3 (17.6) |
| Increase to >ULN | 2 (3.6) | 0 (0) | 3 (3.5) | 3 (3.5) | 1 (1.4) | 0 (0) | 2 (2.4) | 0 (0) | 0 (0) | 0 (0) | 1 (5.9) |
| Elevated creatinine μmol/L | |||||||||||
| Grade 1 (1–1.5×ULN) | 0 (0) | 1 (1.6) | 2 (2.4) | 1 (1.2) | 0 (0) | 2 (2.4) | 1 (1.2) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Grade 2 (1.5–3×ULN) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Grade 3 (3–6×ULN) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Grade 4 (>6×ULN) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Elevated ALT | |||||||||||
| Grade 1 (1–2.5×ULN) | 3 (5.4) | 6 (9.5) | 9 (10.6) | 10 (11.6) | 10 (14.5) | 7 (8.2) | 7 (8.3) | 0 (0) | 3 (20.0) | 1 (5.3) | 0 (0) |
| Grade 2 (2.5–5×ULN) | 1 (1.8) | 0 (0) | 1 (1.2) | 2 (2.4) | 0 (0) | 0 (0) | 1 (1.2) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Grade 3 (5–20×ULN) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Grade 4 (>20×ULN) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0 | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Elevated AST | |||||||||||
| Grade 1 (1–2.5×ULN) | 1 (1.8) | 5 (7.9) | 8 (9.4) | 10 (11.6) | 6 (8.7) | 9 (10.6) | 9 (10.7) | 1 (6.7) | 0 (0) | 1 (5.3) | 3 (17.6) |
| Grade 2 (2.5–5×ULN) | 0 (0) | 0 (0) | 0 (0) | 2 (2.3) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Grade 3 (5–20×ULN) | 0 (0) | 0 (0) | 1 (1.2) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Grade 4 (>20×ULN) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Ratio LDL/HDL | |||||||||||
| Increase to >ULN | 5 (8.9) | 9 (14.3) | 10 (11.8) | 6 (7.0) | 3 (4.3) | 5 (5.9) | 2 (2.4) | 0 (0) | 0 (0) | 3 (15.8) | 3 (17.6) |
†Appendicitis.
‡Pneumonia, diabetic gangrene, subcutaneous abscess.
§Erysipelas.
¶Intervertebral discitis+pneumonia+septic shock.
*Non-responders defined as patients who had not achieved a 20% improvement in swollen joint count based on 66 joints (SJC66) and tender joint count based on 68 joints (TJC68) by Week 12. Patients on placebo were reassigned to receive filgotinib 100 mg once daily or 50 mg twice daily; patients who were receiving filgotinib 50 mg once daily were reassigned to receive filgotinib 100 mg once daily, and patients on filgotinib 25 mg twice daily received filgotinib 50 mg twice daily, continuing on their new dose until week 24.
**One subject had a pretreatment AE (decreased lymphocyte count) that was ongoing throughout the study, for which the study medication was permanently discontinued. This AE was not taken into account in this table as it was not a TEAE.
AE, adverse event; ALT, alanine transaminase; AST, aspartate transaminase; HDL, high-density lipoprotein; LDL, low-density lipoprotein; LLN, lower limit of normal; N, number of patients per group; n, number of patients with event; NK, natural killer; SAE, serious adverse event; TEAE, treatment-emergent adverse event; ULN, upper limit of normal.