EULAR: Tocilizumab (Actemra) Demonstrates Efficacy in Anti-TNF Refractory RA Patients

By Peggy Peck
PARIS, 14 june 2008-- An investigational compound, tocilizumab (Actemra) appears to be an effective option for rheumatoid arthritis patients who are refractory to anti-tumor necrosis factor therapy, researchers reported here.Half of the patients treated with 8 mg/kg of tocilizumab added to methorexate had at least at 20% improvement in arthritis symptoms compared with a 10% improvement in the control group (P<0.0001), Paul Emery, M.D., of Leeds Teaching Hospitals in Leeds, England, reported at the congress of the European League Against Rheumatism (EULAR). And 30.1% achieved disease remission as measured by the Disease Activity Score 28 (DAS28) versus 1.6% of controls (P<0.0001).
Tocilizumab is a humanized interleukin-6 receptor-inhibiting monoclonal antibody.
Patients who are refractory to one or more courses of anti-TNF therapy have very limited options, so the findings of this trial may have significant impact on clinical management for a select group of patients who are "particularly responsive to IL-6 inhibition," Dr. Emery said.
The RADIATE trial randomized 499 patients with moderate to severe rheumatoid arthritis to 4 mg/kg tocilizumab, 8 mg/kg tocilizumab, or placebo. All patients received methotrexate as background therapy. The analysis was based on an intention to treat analysis with data from 489 patients.
The primary endpoint was an improvement of 20% in arthritis signs and symptoms (ACR20).
After 24 weeks, 50% of the 170 patients randomized to the 8 mg/kg dose achieved ACR20 compared with 30.4% of the 161 patients in the 4 mg/kg group, which was also significant compared with controls (P<0.0001).
Moreover, 28.8% of patients who received 8 mg/kg had at least a 50% improvement in symptoms (P<0.0001) and 12.4% had a 70% improvement (P=0.0002).
Serious adverse events were reported by 11% of the patients in the control group, 7% of those in the 4 mg/kg group, and 6% of patients who received 8 mg/kg.
Infections were reported in 41% of controls, 47% of patients in the low dose arm and 50% of patients in the high dose arm. The serious infection rate was 3%, 2%, and 5% in the control, 4 mg/kg, and 8 mg/kg groups, respectively.
The study was funded by Roche, which is developing tocilizumab. Dr. Emery disclosed funding support from Roche.
Primary source: EULAR 2008Source reference:Emery P, et al "Tocilizumab (TCZ) significantly improves disease outcomes in patients with rheumatoid arthritis whose anti-tnf therapy failed: the RADIATE study" EULAR 2008; Abstract OP-0251.