Table 3

Adverse events (AEs, safety population)

Double-blind periodOpen-label period
Placebo
QW SC
n=44
Tocilizumab
162 mg QW SC
n=43
Placebo-tocilizumab
162 mg QW SC
n=31
Continuous-tocilizumab
162 mg QW SC
n=30
Exposure, PY36.834.530.630.3
AEs, n244283126153
 Rate/100 PY (95% CI)663.5 (582.9 to 752.2)820.6 (727.8 to 922.0)412.4 (343.5 to 491.0)504.4 (427.6 to 590.9)
SAEs, n2823115
 Rate/100 PY (95% CI)76.1 (50.6 to 110.0)66.7 (42.3 to 100.1)36.0 (18.0 to 64.4)16.5 (5.4 to 38.5)
 Patients with ≥1 SAE, n (%)16 (36.4)14 (32.6)7 (22.6)4 (13.3)
 Patients with ≥1 serious infection, n (%)*3 (6.8)9 (20.9)4 (12.9)0
AEs leading to death, n1300
 Rate/100 PY2.728.700.000.00
Patients with AEs leading to withdrawal, n (%)5 (11.4)6 (14.0)4 (12.9)†0
 Rate/100 PY13.6017.4013.090.00
Patients with injection site reactions, n*2 (4.5)3 (7.0)4 (12.9)1 (3.3)
SAEs according to system organ class,‡ number of events (rate/100 PY [95% CI])
 Infections and infestations4 (10.9 [3.0 to 27.9])12 (34.8 [18.0 to 60.8])6 (19.6 [7.2 to 42.7])0 (0.0 [0.0 to 12.2])
 Cardiac disorders5 (23.6 [4.4 to 31.7])1 (2.9 [0.1 to 16.2])0 (0.0 [0.0 to 12.1])1 (3.3 [0.1 to to 18.4])
 Gastrointestinal disorders6 (16.3 [6.0 to 35.5])1 (2.9 [0.1 to 16.2])0 (0.0 [0.0 to 12.1])0 (0.0 [0.0 to 12.2])
 Musculoskeletal and connective tissue disorders2 (5.4 [0.7 to 19.7])2 (5.8 [0.7 to 21.0])1 (3.3 [0.1 to 18.2])0 (0.0 [0.0 to 12.2])
 Skin and subcutaneous tissue disorders2 (5.4 [0.7 to 19.7])2 (5.8 [0.7 to 21.0])0 (0.0 [0.0 to 12.1])1 (3.3 [0.1 to 18.4])
 Vascular disorders4 (10.9 [3.0 to 27.9])1 (2.9 [0.1 to 16.2])0 (0.0 [0.0 to 12.1])0 (0.0 [0.0 to 12.2])
 Blood and lymphatic system disorders1 (2.7 [0.1 to 15.2])1 (2.9 [0.1 to 16.2])1 (3.3 [0.1 to 18.2])0 (0.0 [0.0 to 12.2])
 Renal and urinary disorders2 (5.4 [0.7 to 19.7])0 (0.0 [0.0 to 10.7])1 (3.3 [0.1 to 18.2])0 (0.0 [0.0 to 12.2])
 General disorders and administration site conditions0 (0.0 [0.0 to 10.0])2 (5.8 [0.7 to 21.0])0 (0.0 [0.0 to 12.1])0 (0.0 [0.0 to 12.2])
 Neoplasms, benign, malignant and unspecified0 (0.0 [0.0 to 10.0])0 (0.0 [0.0 to 10.7])1 (3.3 [0.1 to 18.2])1 (3.3 [0.1 to 18.4])
 Nervous system disorders2 (5.4 [0.7 to 19.7])0 (0.0 [0.0 to 10.7])0 (0.0 [0.0 to 12.1])0 (0.0 [0.0 to 12.2])
 Endocrine disorders0 (0.0 [0.0 to 10.0])0 (0.0 [0.0 to 10.7])0 (0.0 [0.0 to 12.1])1 (3.3 [0.1 to 18.4])
 Psychiatric disorders0 (0.0 [0.0 to 10.0])1 (2.9 [0.1 to 16.2])0 (0.0 [0.0 to 12.1])0 (0.0 [0.0 to 12.2])
 Reproductive system and breast disorders0 (0.0 [0.0 to 10.0])0 (0.0 [0.0 to 10.7])0 (0.0 [0.0 to 12.1])1 (3.3 [0.1 to 18.4])
 Respiratory, thoracic and mediastinal disorders0 (0.0 [0.0 to 10.0])0 (0.0 [0.0 to 10.7])1 (3.3 [0.1 to 18.2])0 (0.0 [0.0 to 12.2])
  • *Multiple occurrences in the same patient are counted once.

  • †Osteomyelitis (one case serious, one case not serious), scleroderma renal crisis and breast cancer metastatic.

  • ‡According to the Medical Dictionary for Regulatory Activities, version 18.0.

  • AEs, adverse events; PY, patient-years; QW, every week; SAEs, serious adverse events; SC, subcutaneously.