Table 1.

Study design and treatment features of tocilizumab phase III randomized controlled trials and open-label extensions.

StudyPatient PopulationTreatment DurationTreatmentCombination TherapyRescue TherapyaEfficacy Population*, n = 3986All-exposed Safety Population*, n = 4009All-control Safety Population**, n = 4199b
Randomized Controlled Studies
  LITHE N = 1196cModerate to severe active RA
MTX-IR
2 yrsTCZ 4 mg/kg Q4W
TCZ 8 mg/kg Q4We
Placebo Q4W
MTX 10–25 mg QWWk 16: blinded TCZ 4 mg/kg (from placebo) or 8 mg/kg (from 4 mg/kg)
After 12 wks of escape 1 treatment: TCZ 8 mg/kg
DMARD-IR group: n = 1149n = 1149 initially randomly assigned to:
Control: n = 351
TCZ 4 mg/kg: n = 399
TCZ 8 mg/kg: n = 399
Control: n = 392
TCZ 4 mg/kg: n = 399
TCZ 8 mg/kg: n = 399
  OPTION N = 623cModerate to severe active RA
MTX-IR
24 wksTCZ 4 mg/kg Q4W
TCZ 8 mg/kg Q4W
Placebo Q4W
MTX 10–25 mg QWWk 16: TCZ 8 mg/kgDMARD-IR group: n = 597n = 597 initially randomly assigned to:
Control: n = 179
TCZ 4 mg/kg: n = 212
TCZ 8 mg/kg: n = 206
Control: n = 204
TCZ 4 mg/kg: n = 212
TCZ 8 mg/kg: n = 206
  TOWARD N = 1220cModerate to severe active RA
DMARD-IR
24 wksTCZ 8 mg/kg Q4W
Placebo Q4W (randomized 2:1)
DMARDWk 16: adjustment of background DMARDDMARD-IR group: n = 1158n = 1158 initially randomly assigned to:
Control: n = 356
TCZ 8 mg/kg: n = 802
Control: n = 414
TCZ 8 mg/kg: n = 802
  RADIATE N = 499cModerate to severe active RA
TNF-IR
24 wksTCZ 4 mg/kg Q4W
TCZ 8 mg/kg Q4W
Placebo Q4W
MTX 10–25 mg QWWk 16: TCZ 8 mg/kgTNF-IR group: n = 464n = 464 initially randomly assigned to:
Control: n = 126
TCZ 4 mg/kg: n = 163
TCZ 8 mg/kg: n = 175
Control: n = 160
TCZ 4 mg/kg: n = 163
TCZ 8 mg/kg: n = 175
  AMBITION N = 673cActive RA
No MTX during last 6 mo and no MTX failure
24 wksTCZ 8 mg/kg Q4Wf
MTX 7.5–20 mg weekly
Substudy: placebo 8 wks then TCZ 8 mg/kg
Q4W for 16 wks
NoneSubstudy only up to wk 8: TCZ 8 mg/kgNE/NF MTX group: n = 618n = 618 initially randomly assigned to:
Control: n = 330
TCZ 8 mg/kg: n = 288
Control: n = 385g
TCZ 8 mg/kg: n = 288
  Phase 1 Drug Interaction N = 23RA patientsSingle doseTCZ 10 mg/kg
TCZ 10 mg/kg + simvastatin on days 1, 15, and 43
MTX 10–25 mg QWNANAn = 23 initially randomly assigned to: TCZ 10 mg/kg: n = 23NA
Longterm Extension, Open-label Studies
  LITHE extension phase N = 909dOngoing study; moderate to severe active RA
MTX-IR
3 yrs (planned)TCZ 8 mg/kg Q4WMTX 10–25 mg/wkNANA909NA
  GROWTH95 N = 537Patients completing treatment in OPTION−5 yrs (planned)TCZ 8 mg/kg Q4WMTX 10–25 mg/wkNANA537NA
  GROWTH96 N = 2066Patients completing treatment in AMBITION, RADIATE, TOWARD, and drug interaction study−5 yrs (planned)TCZ 8 mg/kg Q4WStudy dependent
None (AMBITIONf)
MTX, 10–25 mg/wk (RADIATE) Other DMARD (TOWARD)
NANA2066NA
  • Abbreviations

  • * TCZ-treated patients (from controlled and extension studies).

  • ** TCZ- or control-treated (from controlled studies).

  • a Patients who did not attain 20% improvement in swollen joint count (SJC) or tender joint count (TJC) could receive rescue therapy during the randomized phase.

  • b Does not include 23 patients from the phase I clinical pharmacology study and 12 patients initially randomly assigned in the randomized controlled studies who did not receive study treatment: LITHE (n = 6), OPTION (n = 1), TOWARD (n = 4), and RADIATE (n = 1).

  • c No. patients randomly assigned during phase III study.

  • d Estimated no. patients who entered extension phase (study is ongoing; final data not available).

  • e At Week 52, all patients were required to start open-label TCZ 8 mg/kg for Year 2 unless they had attained ≥ 70% improvement in SJC and TJC, allowing them to continue the blinded therapy they were receiving at the end of Year 1 to Week 104.

  • f Patients who attained ≥ 50% reduction in TJC and SJC (assessed from baseline) while receiving initially randomized study treatment at weeks 20 and 24 could opt to continue their current blinded treatment in a transition phase that lasted until the last patient enrolled in AMBITION completed the 24-week randomized phase of the study; 234 AMBITION patients continued to receive TCZ 8 mg/kg monotherapy for all evaluations.

  • g 284 patients from blinded study; 101 patients from placebo substudy. DMARD: disease-modifying antirheumatic drug; IR: inadequate response; MTX: methotrexate; NA: not applicable; NE/NF: never exposed/never failed; QW: once every week; Q4W: once every 4 weeks; RA: rheumatoid arthritis; SJC: swollen joint count; TCZ: tocilizumab; TJC: tender joint count; TNF: tumor necrosis factor.