Table 1

Overview of cumulative AEs and serious AEs (SAEs) at week 97 (safety population*)

Rate/100 PY (95% CI) [no. of events]TCZ-SC 162 mg qw (n=631)TCZ-IV 8 mg/kg q4w (n=631)TCZ-IV–SC (n=186)TCZ-SC–IV (n=48)
24 weeks97 weeks24 weeks97 weeks97 weeks97 weeks
No. of PYs of exposure289.821013.26288.39816.53255.7566.19
SAEs11.73 (8.12 to 16.39) [34]14.61 (12.35 to 17.16) [148]14.91 (10.79 to 20.08) [43]15.43 (12.85 to 18.37) [126]19.55 (14.51 to 25.78) [50]9.06 (3.33 to 19.73) [6]
Serious infections3.11 (1.42 to 5.89) [9]3.95 (2.82 to 5.38) [40]3.47 (1.66 to 6.38) [10]3.92 (2.68 to 5.53) [32]6.65 (3.87 to 10.64) [17]1.51 (0.04 to 8.42) [1]
Opportunistic infections†0.35 (0.01 to 1.92) [1]0.39 (0.11 to 1.01) [4]0 (0 to 1.28) [0]0.24 (0.03 to 0.88) [2]1.17 (0.24 to 3.43) [3]0.00 (0 to 5.57) [0]
Serious hypersensitivity events‡0.69 (0.08 to 2.49) [2]0.49 (0.16 to 1.15) [5]1.04 (0.21 to 3.04) [3]0.24 (0.03 to 0.88) [2]0 (0 to 1.44) [0]0 (0 to 5.57) [0]
Adjudicated malignancies§1.38 (0.38 to 3.53) [4]0.89 (0.41 to 1.69) [9]0.69 (0.08 to 2.51) [2]0.73 (0.27 to 1.60) [6]0.78 (0.09 to 2.82) [2]1.51 (0.04 to 8.42) [1]
Serious GI perforation events¶0 (0 to 1.27) [0]0.10 (0.00 to 0.55) [1]0 (0 to 1.28) [0]0 (0 to 0.45) [0]0.78 (0.09 to 2.82) [2]0 (0 to 5.57) [0]
Serious bleeding events0.88 (0.24 to 2.25) [4]0.49 (0.16 to 1.15) [5]1.00 (0.27 to 2.55) [4]0.86 (0.34 to 1.77) [7]0.39 (0.01 to 2.18) [1]0 (0 to 5.57) [0]
Deaths**0 (0 to 1.27) [0]0.39 (0.11 to 1.01) [4]0.35 (0.01 to 1.93) [1]0.49 (0.13 to 1.25) [4]0.78 (0.09 to 2.82) [2]0 (0 to 5.57) [0]
  • *Data are included from the DB and OL periods for all treatment arms; therefore, safety analyses for the TCZ-IV and TCZ-SC arms include all data from patients who received TCZ-IV and TCZ-SC, respectively, up to week 24 (n=631 for each arm) as well as those who remained on TCZ-IV and TCZ-SC during the OL period.

  • †Excludes tuberculosis. Up to the week 97 data cut-off, there was one case of latent tuberculosis in the TCZ-SC arm and zero in the other arms. In the TCZ-SC arm, there was one case each of serious atypical pneumonia, serious bronchopulmonary aspergillosis, non-serious oropharyngeal candidiasis and serious pharyngeal abscess. In the TCZ-IV arm, events included one case each of non-serious genital herpes zoster and non-serious lepromatous leprosy. The events in the TCZ-IV–SC arm were one case each of non-serious genital herpes zoster, non-serious oropharyngeal candidiasis and serious Burkholderia pseudomallei infection (the case occurred in Thailand, recognised as a major endemic region for B. pseudomallei).

  • ‡Serious AEs occurring during or within 24 h of the injection/infusion, excluding injection site reactions, and not deemed to be unrelated to treatment by the investigator.

  • §All malignant and unspecified tumours, including non-melanoma skin cancer adverse events, were included.

  • ¶Medically confirmed.

  • **Patients died of shock (Spain), cerebral infarction ×2 (Bulgaria and Russia), thrombosis (the USA), unknown cause (the USA), acute respiratory distress (Canada), sepsis ×2 (Lithuania and the USA), idiopathic pulmonary fibrosis (the USA) and pneumonia (Canada).

  • AE, adverse event; DB, double-blind; GI, gastrointestinal; IV, intravenous; OL, open-label; PY, patient-year; qw, weekly; q4w, every four weeks; SAE, serious adverse event; SC, subcutaneous; TCZ, tocilizumab.