Table 4.
Neutropenia, ALT Elevations, and Adverse Events to Week 24 by Observed Tocilizumab Ctrough Exposure Quartiles
| TCZ 162 mg SC QW | TCZ 162 mg SC Q2W | TCZ 8 mg/kg IV Q4W | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Q1 (n = 131) | Q2 (n = 129) | Q3 (n = 130) | Q4 (n = 129) | Q1 (n = 81) | Q2 (n = 80) | Q3 (n = 80) | Q4 (n = 80) | Q1 (n = 134) | Q2 (n = 135) | Q3 (n = 134) | Q4 (n = 131) | |
| Total patient‐years | 63.3 | 62.1 | 62.6 | 62.2 | 37.5 | 37.0 | 37.1 | 37.0 | 64.7 | 65.0 | 64.7 | 63.3 |
| Total AEs, n (n per 100 PY: 95%CI) | 388 (613: 553–677) | 292 (471: 418–528) | 373 (596: 537–660) | 346 (556: 499–618) | 177 (472: 405–547) | 136 (367: 308–434) | 139 (375: 315–442) | 158 (427: 363–499) | 349 (539: 484–599) | 345 (531: 476–590) | 367 (567: 510– 628) | 356 (563: 506– 624) |
| Infection and infestation AEs, n (n per 100 PY: 95%CI) | 68 (107: 83–136) | 62 (100: (77–128) | 75 (120: 94–150) | 72 (116: 91–146) | 40 (107: 76–145) | 30 (81: 55–116) | 25 (67: 44–99) | 26 (70: 46–103) | 61 (94: 72–121) | 80 (123: 98–153) | 76 (117: 93–147) | 78 (123: 97–154) |
| Neutropenia grade 1, n (%) | 20 (15) | 24 (19) | 33(26) | 26 (20) | 5 (6) | 3 (4) | 12 (15) | 18 (23) | 5 (4) | 9 (7) | 19 (14) | 17 (13) |
| Neutropenia grade 2, n (%) | 9 (7) | 17 (13) | 12 (9) | 27 (21) | 0 (0) | 4 (5) | 5 (6) | 9 (11) | 5 (4) | 9 (7) | 19 (14) | 17 (13) |
| Neutropenia grade 3, n (%) | 1 (1) | 2 (2) | 5 (4) | 2 (2) | 1 (1) | 2 (3) | 4 (5) | 1 (1) | 3 (2) | 2 (2) | 3 (2) | 7 (5) |
| ALT elevation grade 1, n (%) | 69 (59) | 59 (50) | 68 (57) | 49 (40) | 24 (31) | 28 (38) | 32 (44) | 30 (38) | 55 (45) | 52 (44) | 65 (50) | 44 (37) |
| ALT elevation grade 2, n (%) | 4 (3) | 8 (7) | 4 (3) | 1 (1) | 1 (1) | 3 (4) | 2 (3) | 0 (0) | 5 (4) | 5 (4) | 5 (4) | 4 (3) |
| ALT elevation grade 3, n (%) | 2 (2) | 0 (0) | 1 (0.8) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 2 (2) | 1 (1) | 0 (0) | 0 (0) |
| Mean (median) Ctrough, μg/mL | 14.6 (15.4) | 32.7 (33.0) | 47.9 (47.7) | 80.1 (72.5) | 0.2 (0.1) | 3.5 (3.6) | 8.2 (8.1) | 17.9 (16.6) | 4.1 (4.1) | 12.2 (12.0) | 20.2 (19.8) | 38.9 (36.9) |
Q1–Q4 refer to Ctrough exposure quartiles (lowest to highest). There were no cases of grade 4 neutropenia observed. AE, adverse event; ALT, alanine aminotransferase; Ctrough, predose trough concentration; IV, intravenous; PY, patient‐years; Q2W, every 2 weeks; Q4W, every 4 weeks; QW, weekly; SC, subcutaneous; TCZ, tocilizumab.