NEW YORK (Reuters Health) – In combination with methotrexate, tocilizumab, an IL-6 receptor inhibitor, can safely improve the signs and symptoms of rheumatoid arthritis in patients with an inadequate response to anti-tumor necrosis factor (TNF) biologicals, new research shows.
“This is the first study looking at the impact of blocking the effects of interleukin-6 in patients who have failed TNF antagonist therapy,” lead author Dr. Paul Emery, from the University of Leeds, UK, told Reuters Health. “The ‘take-home’ message is that IL-6 blockade offers a realistic alternative for (these) patients.”
As reported in the Annals of Rheumatic Diseases for November, Dr. Emery’s team assessed the outcomes of 499 rheumatoid arthritis patients with an inadequate response to anti-TNF therapy who were randomized to tocilizumab, at one of two doses (4 mg/kg or 8 mg/kg), or placebo, intravenously every 4 weeks for 24 weeks. All of the patients were also treated with methotrexate.
At 24 weeks, 50.0% and 30.4% of patients treated with 8 mg/kg or 4 mg/kg doses of tocilizumab had an American College of Rheumatology (ACR) 20 response, a standard measure of therapeutic efficacy. By contrast, the percentage achieving this in the placebo group was just 10.1% (p < 0.001).
The authors found that tocilizumab therapy was effective, regardless of the most recently failed TNF antagonist or the number of failed agents. “The finding of equal efficacy after one or two TNF antagonist failures was unusual,” Dr. Emery said.
The disease remission rates in the 8 mg/kg and 4 mg/kg tocilizumab groups were 30.1% and 7.6%, respectively, whereas the rate in the placebo group was only 1.6%.
Roughly 85% of patients in each tocilizumab group and 81% in the placebo group experienced an adverse event, but in nearly all cases the side effect was mild or moderate and easily managed. Infections, gastrointestinal symptoms, rash, and headache were all more common with the active agent than with placebo. Serious events were actually more common with placebo.
“Once tocilizumab becomes licensed in other countries as it is currently in Japan, we will have further expanded the therapeutic options that in turn will allow an increase in the proportion of rheumatoid arthritis patients who achieve a good clinical outcome,” Dr. Josef S. Smolen, from the Medical University of Vienna, Austria, and Dr. Michael E. Weinblatt, from Harvard Medical School, Boston, comment in a related editorial.”
On September 18, 2008 Roche, the manufacturer received from the U.S. Food and Drug Administration (FDA) a complete response letter for the Biologics License Application (BLA) for ACTEMRA® (tocilizumab) to treat patients with moderately to severely active rheumatoid arthritis.
Ann Rheum Dis 2008;67:1497-1498,1516-1523.