Abstract 2089: Targeted Inhibition of the IL-6 Receptor with Tocilizumab Effectively Reduces Disease Activity in Patients with Rheumatoid Arthritis
Authors
AD Beaulieu, A Rubbert-Roth, T Woodworth, E Alecock, R Alten, J Smolen
Purpose:
This was a phase III randomized double-blind placebo controlled study of tocilizumab (TCZ), in patients with moderate to severe active RA despite treatment with methotrexate (MTX). These results have been previously summarized at EULAR 2007.
Methods:
623 patients were evaluated. Patients received either 8 mg/kg TCZ, 4 mg/kg TCZ, or placebo IV every 4 weeks. All groups received stable MTX pre-study doses (10-25 mg weekly)
Results:
A significantly higher proportion of TCZ-treated patients showed improvements in ACR20 at 24 weeks (TCZ 8 mg/kg 59%; TCZ 4 mg/kg 48%; placebo 27%). Significantly more patients also achieved ACR50 and ACR70 response by 24 weeks with TCZ 8 mg/kg and TCZ 4 mg/kg vs. placebo (ACR50: 44% and 32% vs. 11%, respectively; ACR70: 22% and 12% vs. 2%, respectively). All results for TCZ were significant compared to placebo. An ACR90 response was achieved by 5.4% with TCZ 8 mg/kg and 4.7% with TCZ 4 mg/kg vs. none for placebo. CRP levels dropped to normal at 2 weeks’ treatment with 8 mg/kg TCZ and remained normal to study end. A similar frequency of adverse events (AEs) was reported in all groups. Of 41 serious AEs affecting approximately 6% of patients in each group, 15 were considered related to study treatment and 11 led to discontinuation of treatment. Increases in ALT greater than 3> ULN was seen in 2.9% of placebo, 4.2% of TCZ 4m/kg, and 7.8% of 8 mg/kg without associated increases in bilirubin or clinical hepatitis. Serious infections were observed with a higher frequency in patients treated with TCZ (2.9% in the TCZ 8 mg/kg group, 1.4% in the TCZ 4 mg/kg group and 1% in the placebo group).
Conclusions:
This large phase 3 study confirmed the efficacy of TCZ in patients with active RA on background MTX.
Editorial Comment:
The studies presented at ACR 2007 demonstrate that inhibition of the cytokine IL-6 using tocilizumab results in clinical improvements in RA over 24 weeks. Longer term efficacy and safety data is needed, and additional information regarding possible structure modification with this compound is also awaited. The long term safety implications of elevated lipid levels and LFT increases need to be further clarified.
