Key ACTEMRA/RoACTEMRA publication summaries
Humanized antibody to human interleukin-6 receptor inhibits the development of collagen arthritis in cynomolgus monkeys
Mihara M, Kotoh M, Nishimoto N, Oda Y, Kumagai E, Takagi N, Tsunemi K, Ohsugi Y, Kishimoto T, Yoshizaki K, Takeda Y.
Clin Immunol 2001; 98:319–326.
This study aimed to investigate the anti-arthritic effect of the humanised anti-IL-6 receptor antibody MRA (subsequently named tocilizumab and referred to as TCZ here) in a collagen-induced arthritis (CIA) model in cynomolgus monkeys (N=15).
CIA was induced and monkeys received either TCZ 1 mg/kg (n=5), TCZ 10 mg/kg (n=5) or vehicle (phosphate buffer) control (n=5) intravenously once a week, from the day of the first collagen immunisation, for 13 weeks.
Key study results are summarised below.
- The TCZ 10 mg/kg dose significantly inhibited the development of arthritis compared with control. Four of the five monkeys showed no signs of stiff or swollen joints throughout the study (p<0.05 vs. control).
- In the 1 mg/kg group, only two of the five monkeys showed no signs of stiff or swollen joints.
- CIA-induced increases in C-reactive protein, fibrinogen and erythrocyte sedimentation rate were almost completely suppressed by TCZ 10 mg/kg. The 1 mg/kg dose had little effect on these parameters.
- Radiographic and histological joint changes were evident in all monkeys in the control group.
- Four of the five monkeys in the TCZ 10 mg/kg group showed no sign of radiographic or histological changes.
- Anti-TCZ antibody was detected in all monkeys in the 1 mg/kg group and two of the five monkeys in the 10 mg/kg group.
- Serum TCZ concentrations remained high (over 100 mg/ml) throughout the study in the 10 mg/kg group, but were negligible in the 1 mg/kg group.
This study indicated that IL-6 plays an important role in monkey CIA and provided supportive evidence of the potential therapeutic benefit of targeting the IL-6 pathway with TCZ in patients with RA