Maini RN, Taylor PC, Szechinski J, Pavelka K, Bröll J, Balint G, Emery P, Raemen F, Petersen J, Smolen J, Thomson D, Kishimoto T; for the CHARISMA Study Group.
Arthritis Rheum 2006; 54:2817–2829.
The CHARISMA study was a 20-week, double-blind, randomised, placebo-controlled, Phase II study conducted in Japan to establish the safety and efficacy of repeat infusions of tocilizumab (TCZ) alone or in combination with methotrexate (MTX) in patients with established RA who had an inadequate response to MTX (N=359).
During the 20-week study, TCZ (2 mg/kg, 4 mg/kg or 8 mg/kg) was given as monotherapy (by discontinuation of MTX) or in combination with MTX and compared with MTX alone (control). Baseline demographics of the treatment groups were comparable, with no significant differences observed between groups.
Key study results are summarised below.
- At Week 16, 61% and 63% of patients receiving TCZ monotherapy (4 mg/kg and 8 mg/kg, respectively) achieved the primary endpoint of an ACR20 response compared with 41% of the control group (p<0.05).
- In the combination therapy groups, the proportion of patients achieving an ACR20 response was significantly higher in all TCZ doses (2, 4 or 8 mg/kg) compared with the control group (64%, 63% and 74%, respectively) at Week 16.
- Only the TCZ 8 mg/kg dose + MTX was significantly better than the control group in terms of ACR50 (53% vs. 29%) and ACR70 (37% vs. 16%) responses.
- All groups receiving TCZ, alone or in combination with MTX (except TCZ 2 mg/kg monotherapy), showed a significant decrease in DAS28 at Week 16 compared with the control group.
- Decreases in DAS28 were dose-dependent: a greater proportion of patients in the TCZ 8 mg/kg alone (34%) or in combination with MTX (17%) groups achieved DAS28 remission (<2.6) compared with the control group (8%).
- In general, TCZ was well tolerated in this study.
- Serious infections were reported by three patients in the 8 mg/kg TCZ + MTX group (n=50) and by four patients in the 2 mg/kg monotherapy TCZ group (n=53).
The authors conclude that targeted blockade of the IL-6 pathway is highly efficacious and that TCZ monotherapy or TCZ in combination with MTX is well tolerated in this patient population, having a safety profile consistent with other biologics.
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