OP-0251 – Tocilizumab Significantly Improves Disease Outcomes in Patients with Rheumatoid Arthritis Whose Anti-TNF Therapy Failed: the RADIATE Study
Emery, Keystone, Tony, Cantagrel, van Vollenhoven, Sanchez, Alecock, Lee, Kremer; Leeds, United Kingdom
Objectives
Tocilizumab (TCZ) is a monoclonal antibody directed against the IL-6 receptor, blockade of which represents a novel molecular target for RA. IL-6, like TNF-α, is a key regulatory cytokine at the center of RA pathogenesis. Efficacy and safety studies for TCZ in patients with an inadequate response to methotrexate have been presented here previously.
Methods
Patients with moderate to severe active RA despite prior treatment with at least one TNF inhibitor were randomized equally to receive monthly infusions of TCZ 4 mg, 8 mg, or placebo. All patients continued background methotrexate, but other DMARDs and TNF inhibitors were discontinued prior to enrollment. The primary efficacy outcome was the proportion of patients achieving an ACR20 response at 24 weeks. Safety was assessed throughout.
Results
There were 499 patients randomized approximately equally into the three groups. Patients were primarily female with a mean of 52 years at baseline. The mean duration of RA was 11 years. Patients had active disease, on average, with mean swollen and tender joint counts of 19 and 31 joints, respectively, and a mean DAS28 of 6.8. Baseline characterisitics were balanced between groups. About half of the enrolled patients had previously failed only 1 TNF inhibitor, but approximately 15% had failed three prior TNF inhibitors. The proportions of patients completing 24 weeks of double-blind treatment were 79%, 85%, and 87% for the placebo, 4, and 8 mg TCZ groups, respectively.
Efficacy Outcomes at 24 weeks by Treatment Allocation
|
Placebo |
TCZ 4 mg |
TCZ 8 mg |
ACR20 |
10 |
30 |
50 |
ACR50 |
4 |
17 |
29 |
ACR70 |
1 |
5 |
12 |
DAS28 Remission |
2 |
8 |
30 |
Serious adverse events and infections were not different by treatment group. There was no difference in ACR20 response by number or timing of previous TNF inhibitors. Increases in LDL, HDL, and total cholesterol were noted in the active treatment groups consistent with prior trials of TCZ.
Conclusions
TCZ treatment was safe and more efficacious than placebo at relieving the signs and symptoms of moderate to severe RA in patients with a previous inadequate response to at least one TNF inhibitor.
Editorial Comment
Responses are not as robust here as those seen in prior clinical trials of TCZ in methotrexate non-responders. This could be due to diminished efficacy in this patient population or because the placebo response is much smaller here than in the other trials. Regardless, TCZ is a promising novel therapeutic that will likely prove useful in patients with RA that is highly driven by IL-6. Identifying predictors for patients who may benefit from IL-6 inhibition, rather than TNF inhibition, will play an important role in determining the proper placement of this agent in the RA therapeutic armamentarium. Likewise, future studies will establish longterm safety and durability, and clarify issues related to the observation of increased lipids.
