Safety variables of special interest
| Placebo controlled | Extended | All-Bari-SLE (N=1655) | ||||
| Placebo (N=635) | Bari 2 mg (N=641) | Bari 4 mg (N=634) | Bari 2 mg (N=641) | Bari 4 mg (N=634) | ||
| Exposure | ||||||
| Total patient-years | 503.4 | 507.9 | 496 | 896.1 | 876.2 | 2164.2 |
| No of patients with ≥52 weeks, n (%) | 313 (49.3) | 313 (48.8) | 298 (47.0) | 403 (62.9) | 391 (61.7) | 1012 (61.1) |
| Median duration, days | 363 | 363 | 363 | 528 | 525.5 | 473 |
| Longest exposure, days | 428 | 404 | 393 | 1257 | 1283 | 1283 |
| Adverse events, n (%) IR (95% CI) | ||||||
| Any TEAE | 494 (77.8) 226.5 (206.9, 247.3) | 501 (78.2) 226.2 (206.8, 246.9) | 501 (79.0) 240.3 (219.7, 262.3) | 538 (83.9) 189.1 (173.4, 205.7) | 534 (84.2) 210.4 (193.0, 229.1) | 1318 (79.6) 174.5 (165.2, 184.2) |
| Mild | 220 (34.6) 54.8 (47.8, 62.6) | 215 (33.5) 53.3 (46.5, 61.0) | 218 (34.4) 56.1 (48.9, 64.1) | 209 (32.6) 29.4 (25.6, 33.7) | 187 (29.5) 26.0 (22.4, 30.0) | 496 (30.0) 28.0 (25.6, 30.6) |
| Moderate | 235 (37.0) 60.2 (52.7, 68.4) | 232 (36.2) 56.9 (49.8, 64.7) | 227 (35.8) 57.7 (50.4, 65.7) | 255 (39.8) 38.2 (33.6, 43.2) | 257 (40.5) 39.3 (34.6, 44.4) | 634 (38.3) 38.5 (35.5, 41.6) |
| Severe | 39 (6.1) 7.7 (5.5, 10.5) | 54 (8.4) 10.6 (7.9, 13.8) | 56 (8.8) 11.3 (8.5, 14.7) | 74 (11.5) 8.3 (6.5, 10.4) | 90 (14.2) 10.5 (8.4, 12.9) | 188 (11.4) 8.7 (7.5, 10.0) |
| SAE | 46 (7.2) 9.1 (6.7, 12.1) | 73 (11.4) 14.4 (11.3, 18.1) | 68 (10.7) 13.8 (10.7, 17.5) | 107 (16.7) 12.3 (10.1, 14.9) | 112 (17.7) 13.1 (10.8, 15.8) | 262 (15.8) 12.4 (10.9, 14.0) |
| Interruption of study drug due to AE | 161 (25.4) 36.4 (31.0, 42.5) | 166 (25.9) 37.0 (31.6, 43.0) | 172 (27.1) 39.6 (33.9, 46.0) | 211 (32.9) 29.5 (25.7, 33.8) | 223 (35.2) 31.9 (27.9, 36.4) | 520 (31.4) 29.5 (27.0, 32.1) |
| Permanent discontinuation from study drug due to AE | 48 (7.6) 9.3 (6.9, 12.3) | 59 (9.2) 11.3 (8.6, 14.6) | 58 (9.1) 11.4 (8.6, 14.7) | 78 (12.2) 8.3 (6.6, 10.4) | 80 (12.6) 8.8 (6.9, 10.9) | 177 (10.7) 7.8 (6.7, 9.1) |
| Permanent discontinuation from study due to AE | 36 (5.7) 6.9 (4.9, 9.6) | 32 (5.0) 6.1 (4.2, 8.6) | 30 (4.7) 5.9 (3.9, 8.4) | 48 (7.5) 5.1 (3.8, 6.8) | 49 (7.7) 5.3 (4.0, 7.1) | 112 (6.8) 4.9 (4.1, 5.9) |
| Death | 4 (0.6) 0.8 (0.2, 2.0) | 1 (0.2) 0.2 (0.0, 1.1) | 4 (0.6) 0.8 (0.2, 2.0) | 1 (0.2) 0.1 (0.0, 0.6) | 10 (1.6) 1.1 (0.5, 2.0) | 12 (0.7) 0.5 (0.3, 0.9) |
| Infections | ||||||
| Patients with ≥1 TE infection | 311 (49.0) 89.0 (79.4, 99.5) | 325 (50.7) 92.2 (82.4, 102.8) | 322 (50.8) 94.2 (84.2, 105.1) | 385 (60.1) 76.8 (69.4, 84.9) | 380 (59.9) 77.4 (69.9, 85.6) | 901 (54.4) 68.8 (64.4, 73.5) |
| Serious infections | 12 (1.9) 2.3 (1.2, 4.0) | 22 (3.4) 4.2 (2.7, 6.4) | 28 (4.4) 5.5 (3.7, 8.0) | 38 (5.9) 4.2 (2.9, 5.7) | 47 (7.4) 5.3 (3.9, 7.0) | 101 (6.1) 4.6 (3.7, 5.5) |
| Infections that led to permanent discontinuation from study drug | 7 (1.1) 1.3 (0.5, 2.8) | 11 (1.7) 2.1 (1.0, 3.7) | 14 (2.2) 2.7 (1.5, 4.6) | 14 (2.2) 1.5 (0.8, 2.5) | 18 (2.8) 2.0 (1.2, 3.1) | 36 (2.2) 1.6 (1.1, 2.2) |
| Infections that led to temporary interruption from study drug | 82 (12.9) 17.1 (13.6, 21.2) | 98 (15.3) 20.4 (16.6, 24.9) | 91 (14.4) 19.1 (15.4, 23.5) | 139 (21.7) 17.6 (14.8, 20.7) | 135 (21.3) 16.8 (14.1, 19.9) | 325 (19.6) 16.5 (14.7, 18.4) |
| Opportunistic infection | 3 (0.5) 0.6 (0.1, 1.7) | 4 (0.6) 0.8 (0.2, 1.9) | 11 (1.7) 2.2 (1.1, 3.8) | 8 (1.2) 0.9 (0.4, 1.7) | 12 (1.9) 1.3 (0.7, 2.3) | 25 (1.5) 1.1 (0.7, 1.6) |
| Herpes zoster | 18 (2.8) 3.5 (2.1, 5.5) | 17 (2.7) 3.3 (1.9, 5.2) | 30 (4.7) 6.0 (4.0, 8.6) | 27 (4.2) 2.9 (1.9, 4.3) | 44 (6.9) 5.0 (3.7, 6.7) | 81 (4.9) 3.7 (2.9, 4.6) |
| Tuberculosis | 0 | 0 | 1 (0.2) 0.2 (0.0, 1.1) | 1 (0.2) 0.1 (0.0, 0.6) | 1 (0.2) 0.1 (0.0, 0.6) | 3 (0.2) 0.1 (0.0, 0.4) |
| MACE* | ||||||
| Patients with ≥1 MACE | 0 | 1 (0.2) 0.2 (0.0, 1.2) | 4 (0.8) 0.9 (0.2, 2.2) | 2 (0.4) 0.2 (0.0, 0.8) | 7 (1.3) 0.8 (0.3, 1.7) | 11 (0.8) 0.5 (0.3, 0.9) |
| Cardiovascular death | 0 | 0 | 2 (0.4) 0.4 (0.1, 1.6) | 0 | 2 (0.4) 0.2 (0.0, 0.8) | 2 (0.1) 0.1 (0.0, 0.3) |
| Myocardial infarction | 0 | 1 (0.2) 0.2 (0.0, 1.2) | 1 (0.2) 0.2 (0.0, 1.2) | 1 (0.2) 0.1 (0.0, 0.6) | 3 (0.6) 0.3 (0.1, 1.0) | 5 (0.3) 0.2 (0.1, 0.5) |
| Stroke | 0 | 0 | 2 (0.4) 0.4 (0.1, 1.6) | 1 (0.2) 0.1 (0.0, 0.6) | 3 (0.6) 0.3 (0.1, 1.0) | 5 (0.3) 0.2 (0.1, 0.5) |
| VTEs* | ||||||
| DVT and/or PE | 2 (0.4) 0.4 (0.1, 1.5) | 3 (0.6) 0.6 (0.1, 1.8) | 0 | 3 (0.6) 0.3 (0.1, 1.0) | 3 (0.6) 0.3 (0.1, 1.0) | 8 (0.6) 0.4 (0.2 0.7) |
| DVT | 1 (0.2) 0.2 (0.0, 1.2) | 3 (0.6) 0.6 (0.1, 1.8) | 0 | 3 (0.6) 0.3 (0.1, 1.0) | 1 (0.2) 0.1 (0.0, 0.6) | 5 (0.3) 0.2 (0.1, 0.5) |
| PE | 1 (0.2) 0.2 (0.0, 1.2) | 2 (0.4) 0.4 (0.1, 1.5) | 0 | 2 (0.4) 0.2 (0.0. 0.8) | 2 (0.4) 0.2 (0.0, 0.8) | 5 (0.3) 0.2 (0.1, 0.5) |
| Malignancies other than NMSC | 2 (0.3) 0.4 (0.0, 1.4) | 3 (0.5) 0.6 (0.1, 1.7) | 2 (0.3) 0.4 (0.0, 1.4) | 4 (0.6) 0.4 (0.1, 1.1) | 4 (0.6) 0.4 (0.1, 1.1) | 12 (0.7) 0.5 (0.3, 0.9) |
| GI perforations | 0 | 1 (0.2) 0.2 (0.0, 1.1) | 2 (0.3) 0.4 (0.0, 1.4) | 2† (0.3) 0.2 (0.0, 0.8) | 2 (0.3) 0.2 (0.0, 0.8) | 4† (0.2) 0.2 (0.0, 0.4) |
*MACE and VTE were adjudicated in all studies except for the phase 2 study. An additional DVT occurred in the phase 2 study in a patient treated with baricitinib 4 mg, not included in the table. For placebo, baricitinib 2 mg, baricitinib 4 mg and All-Bari-SLE, respectively, N=530, N=536, N=530 and N=1446.
†Includes one patient with perianal abscess who was not considered to have a GI perforation after medical review.
AE, adverse events; bari, baricitinib; CI, confidence interval; DVT, deep vein thrombosis; GI, gastrointestinal; IR, incidence rate; MACE, major adverse cardiovascular event; n, number of patients in the specified category; N, number of patients in the analysis set; NMSC, non-melanoma skin cancer; PE, pulmonary embolism; SAE, serious AE; SLE, systemic lupus erythematosus; TEAE, treatment-emergent adverse event; VTE, venous thromboembolism.