Table 4.
Selected treatment-emergent adverse events
|
Combination therapy with MTX in MTX-IR patients 52 weeks |
Combination therapy with csDMARDs in TNFi-INT/IR patients 24 weeks |
Monotherapy in MTX-INT/IR patients 24 weeks |
Total | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Placebo + MTX |
Sarilumab 150 mg q2w |
Sarilumab 200 mg q2w |
Placebo |
Sarilumab 150 mg q2w |
Sarilumab 200 mg q2w |
Adalimumab 40 mg q2w |
Sarilumab 200 mg q2w |
||
| Patients with ≥ 1 infection, n/N (%) | |||||||||
| With diabetes | 12/27 (44.4) | 12/27 (44.4) | 20/37 (54.1) | 8/23 (34.8) | 10/23 (43.5) | 4/21 (19.0) | 9/16 (56.3) | 3/10 (30.0) | 78/184 (42.4) |
| Without diabetes | 115/370 (31.1) | 156/374 (41.7) | 139/359 (38.7) | 40/158 (25.3) | 30/158 (19.0) | 52/163 (31.9) | 42/168 (25.0) | 50/174 (28.7) | 624/1924 (32.4) |
| Patients with ≥ 1 serious infection, n/N (%) | |||||||||
| With diabetes | 4/27 (14.8) | 1/27 (3.7) | 1/37 (2.7) | 0/23 | 1/23 (4.3) | 0/21 | 0/16 | 0/10 | 7/184 (3.8) |
| Without diabetes | 6/370 (1.6) | 10/374 (2.7) | 14/359 (3.9) | 2/158 (1.3) | 0/158 | 2/163 (1.2) | 2/168 (1.2) | 2/174 (1.1) | 38/1924 (2.0) |
| Patients with infection leading to treatment discontinuation, n/N (%) | |||||||||
| With diabetes | 1/27 (3.7) | 0/27 | 0/37 | 0/23 | 3/23 (13.0) | 0/21 | 0/16 | 0/10 | 4/184 (2.2) |
| Without diabetes | 5/370 (1.4) | 13/374 (3.5) | 11/359 (3.1) | 1/158 (0.6) | 2/158 (1.3) | 5/163 (3.1) | 2/168 (1.2) | 1/174 (0.6) | 40/1924 (2.1) |
| Patients with opportunistic infections (including tuberculosis), n/N (%) | |||||||||
| With diabetes | 0/27 | 0/27 | 1/37 (2.7) | 0/23 | 0/23 | 0/21 | 0/16 | 0/10 | 1/184 (0.5) |
| Without diabetes | 2/370 (0.5) | 2/374 (0.5) | 3/359 (0.8) | 1/158 (0.6) | 0/158 | 2/163 (1.2) | 1/168 (0.6) | 1/174 (0.6) | 12/1924 (0.6) |
| Patients with tuberculosis, n/N (%) | |||||||||
| With diabetes | 0/27 | 0/27 | 0/37 | 0/23 | 0/23 | 0/21 | 0/16 | 0/10 | 0/184 |
| Without diabetes | 0/370 | 0/374 | 0/359 | 0/158 | 0/158 | 0/163 | 1/168 (0.6) | 0/174 | 1/1924 (0.1) |
| Patients with ≥ 1 hypersensitivity, n/N (%) | |||||||||
| With diabetes | 1/27 (3.7) | 1/27 (3.7) | 3/37 (8.1) | 2/23 (8.7) | 3/23 (13.0) | 4/21 (19.0) | 0/16 | 2/10 (20.0) | 16/184 (8.7) |
| Without diabetes | 17/370 (4.6) | 25/374 (6.7) | 26/359 (7.2) | 5/158 (3.2) | 7/158 (4.4) | 7/163 (4.3) | 10/168 (6.0) | 8/174 (4.6) | 105/1924 (5.5) |
| Patients with ≥ 1 serious hypersensitivity, n/N (%) | |||||||||
| With diabetes | 0/27 | 0/27 | 0/37 | 0/23 | 0/23 | 0/21 | 0/16 | 0/10 | 0/184 |
| Without diabetes | 0/370 | 0/374 | 1/359 (0.3) | 0/158 | 0/158 | 0/163 | 1/168 (0.6) | 0/174 | 2/1924 (0.1) |
| Patients with ≥ 1 hypersensitivity leading to treatment discontinuation, n/N (%) | |||||||||
| With diabetes | 0/27 | 0/27 | 1/37 (2.7) | 0/23 | 0/23 | 0/21 | 0/16 | 1/10 (10.0) | 2/184 (1.1) |
| Without diabetes | 1/370 (0.3) | 3/374 (0.8) | 1/359 (0.3) | 0/158 | 0/158 | 1/163 (0.6) | 1/168 (0.6) | 0/174 | 7/1924 (0.4) |
| ANC < 1.5 G/L (non-black patients) or < 1.0 G/L (black patients), n/N (%) | |||||||||
| With diabetes | 1/27 (3.7) | 1/27 (3.7) | 5/37 (13.5) | 0/23 | 1/23 (4.3) | 5/21 (23.8) | 1/16 (6.3) | 3/10 (30.0) | 17/184 (9.2) |
| Without diabetes | 5/370 (1.4) | 72/374 (19.3) | 88/359 (24.5) | 2/158 (1.3) | 30/158 (19.0) | 37/162 (22.8) | 39/167 (23.4) | 59/174 (33.9) | 332/1922 (17.3) |
| Platelets < 50 G/L, n/N (%) | |||||||||
| With diabetes | 0/27 | 0/27 | 0/37 | 0/23 | 0/23 | 0/21 | 0/16 | 0/10 | 0/184 |
| Without diabetes | 0/370 | 0/374 | 2/358 (0.6) | 0/158 | 0/158 | 1/162 (0.6) | 0/0 | 1/174 (0.6) | 4/1921 (0.2) |
| Total cholesterol baseline normal/missing to post baseline ≥ 6.2 mmol/L, n/N (%) | |||||||||
| With diabetes | 6/25 (24.0) | 2/23 (8.7) | 12/30 (40.0) | 6/19 (31.6) | 9/23 (39.1) | 7/20 (35.0) | 2/15 (13.3) | 2/7 (28.6) | 46/162 (28.4) |
| Without diabetes | 62/325 (19.1) | 128/327 (39.1) | 140/315 (44.4) | 18/140 (12.9) | 51/130 (39.2) | 52/141 (36.9) | 35/131 (26.7) | 53/140 (37.9) | 539/1649 (32.7) |
| Total LDL-C baseline normal/missing to post-baseline LDL-C ≥ 4.1 mmol/L, n/N (%) | |||||||||
| With diabetes | 2/25 (8.0) | 3/25 (12.0) | 11/32 (34.4) | 4/21 (19.0) | 7/22 (31.8) | 5/20 (25.0) | 1/15 (6.7) | 2/9 (22.2) | 35/169 (20.7) |
| Without diabetes | 41/344 (11.9) | 82/342 (24.0) | 101/334 (30.2) | 10/148 (6.8) | 39/146 (26.7) | 38/151 (25.2) | 28/142 (19.7) | 40/153 (26.1) | 379/1760 (21.5) |
| Total triglycerides baseline normal/missing to post-baseline ≥ 4.6 mmol/L, n/N (%) | |||||||||
| With diabetes | 2/27 (7.4) | 0/0 | 3/36 (8.3) | 0/23 | 1/23 (4.3) | 0/21 | 1/16 (6.3) | 1/10 (10.0) | 8/181 (4.4) |
| Without diabetes | 1/368 (0.3) | 11/372 (3.0) | 13/358 (3.6) | 1/157 (0.6) | 5/153 (3.3) | 6/161 (3.7) | 4/164 (2.4) | 3/173 (1.7) | 44/1906 (2.3) |
| ALT > 3 to ≤ 5 ULN, n/N (%) | |||||||||
| With diabetes | 0/27 | 0/27 | 6/37 (16.2) | 0/23 | 0/23 | 0/21 | 2/16 (12.5) | 0/10 | 8/184 (4.3) |
| Without diabetes | 9/370 (2.4) | 33/374 (8.8) | 25/359 (7.0) | 2/158 (1.3) | 4/157 (2.5) | 7/161 (4.3) | 10/167 (6.0) | 11/174 (6.3) | 101/1920 (5.3) |
| ALT > 5 to ≤ 10 ULN, n/N (%) | |||||||||
| With diabetes | 0/27 | 0/27 | 2/37 (5.4) | 0/23 | 0/23 | 0/21 | 1/16 (6.3) | 0/10 | 3/184 (1.6) |
| Without diabetes | 1/370 (0.3) | 11/374 (2.9) | 8/359 (2.2) | 0/158 | 0/158 | 0/161 | 2/167 (1.2) | 3/174 (1.7) | 25/1920 (1.3) |
ALT alanine aminotransferase, ANC absolute neutrophil count, csDMARD conventional synthetic disease-modifying antirheumatic drug, INT intolerant, IR inadequate response, LDL-C low-density lipoprotein cholesterol, MTX methotrexate, q2w every 2 weeks, TNFi tumour necrosis factor α inhibitor, ULN upper limit of normal