| 8 mg/kg Tocilizumab + methotrexate (n = 175) | 4 mg/kg Tocilizumab + methotrexate (n = 163) | Placebo + methotrexate (n = 160) | |||||||||||||||
| Overall summary of AE, serious AE and deaths* | |||||||||||||||||
| Total AE, n (%) | 147 (84.0) | 142 (87.1) | 129 (80.6) | ||||||||||||||
| Severe AE† | 24 (13.7) | 22 (13.5) | 31 (19.4) | ||||||||||||||
| Related AE | 111 (63.4) | 107 (65.6) | 86 (53.8) | ||||||||||||||
| Total serious AE, n (%) | 11 (6.3) | 12 (7.4) | 18 (11.3) | ||||||||||||||
| Related serious AE | 5 (2.9) | 3 (1.8) | 3 (1.9) | ||||||||||||||
| Serious infections | 8 (4.6) | 3 (1.8) | 5 (3.1) | ||||||||||||||
| AE leading to discontinuation, n (%) | 10 (5.7) | 10 (6.1) | 8 (5.0) | ||||||||||||||
| AE leading to dose modification, n (%) | 12 (6.9) | 24 (14.7) | 13 (8.1) | ||||||||||||||
| Deaths | 0 | 0 | 0 | ||||||||||||||
| Summary of AE by class in >5% of patients | |||||||||||||||||
| Infections and infestations, n (%) | 86 (49.1) | 76 (46.6) | 66 (41.3) | ||||||||||||||
| Gastrointestinal, n (%) | 64 (36.6) | 53 (32.5) | 31 (19.4) | ||||||||||||||
| Skin and subcutaneous tissue, n (%) | 38 (21.7) | 50 (30.7) | 23 (14.4) | ||||||||||||||
| Musculoskeletal and connective tissue, n (%) | 27 (15.4) | 34 (20.9) | 34 (21.3) | ||||||||||||||
| Nervous system, n (%) | 32 (18.3) | 32 (19.6) | 27 (16.9) | ||||||||||||||
| General and administrative, n (%) | 21 (12.0) | 26 (16.0) | 23 (14.4) | ||||||||||||||
| Respiratory, n (%) | 21 (12.0) | 24 (14.7) | 21 (13.1) | ||||||||||||||
| Injuries and procedural, n (%) | 19 (10.9) | 11 (6.7) | 16 (10.0) | ||||||||||||||
| Laboratory investigations, n (%) | 14 (8.0) | 20 (12.3) | 9 (5.6) | ||||||||||||||
| Vascular, n (%) | 14 (8.0) | 18 (11.0) | 8 (5.0) | ||||||||||||||
| Psychiatric, n (%) | 13 (7.4) | 16 (9.8) | 6 (3.8) | ||||||||||||||
| Eye, n (%) | 11 (6.3) | 11 (6.7) | 3 (1.9) | ||||||||||||||
| Metabolism and nutrition, n (%) | 9 (5.1) | 7 (4.3) | 7 (4.4) | ||||||||||||||
| Haematological, n (%) | 9 (5.1) | 4 (2.5) | 4 (2.5) | ||||||||||||||
| Summary of serious AE by class in >1% of patients | |||||||||||||||||
| Infections and infestations, n (%) | 8 (4.6%) | 3 (1.8%) | 5 (3.1%) | ||||||||||||||
| Musculoskeletal and connective tissue, n (%) | 1 (0.6%) | 2 (1.2%) | 5 (3.1%) | ||||||||||||||
| Gastrointestinal, n (%) | 2 (1.1%) | 2 (1.2%) | 2 (1.3%) | ||||||||||||||
| Summary of changes in lipid parameters‡ | |||||||||||||||||
| Total cholesterol, mmol/l | |||||||||||||||||
| Baseline, mean (SD) | 5.09 (1.07) | 4.96 (1.12) | 4.92 (0.99) | ||||||||||||||
| Week 24, mean (SD) | 5.99 (1.25) | 5.38 (1.09) | 4.99 (1.07) | ||||||||||||||
| High-density lipoprotein, n (%) | |||||||||||||||||
| No change | 112 (64.7) | 100 (61.3) | 104 (65.0) | ||||||||||||||
| Elevation to ⩾60 mg/dl | 29 (16.6) | 22 (13.5) | 6 (3.8) | ||||||||||||||
| Low-density lipoprotein, n (%) | |||||||||||||||||
| No change | 90 (51.4) | 76 (46.6) | 104 (65.0) | ||||||||||||||
| Elevation to ⩾160 mg/dl | 21 (12.0) | 25 (15.3) | 6 (3.8) | ||||||||||||||
*Events that occurred on escape therapy were excluded from all treatment groups presented in this table.
†Severe adverse events refer to those resulting in an inability of the patient to work or perform daily activity.
‡Changes according to ATPIII guidelines20 reflect highest elevation of lipid during study.
AE, adverse event.