Tocilizumab Effective In Refractory Rheumatoid Arthritis Patients

New phase 3 data demonstrate that the investigational agent tocilizumab (Actemra), given with stable methotrexate, is effective in patients with active rheumatoid arthritis who have responded inadequately to tumor necrosis factor (TNF) antagonists.


The findings, reported here at the European Union League Against Rheumatism (EULAR) 2008, also show that treatment was generally well tolerated.


Tocilizumab is a monoclonal antibody that is specific for the human interleukin (IL)- 6 receptor, a key cytokine in the inflammatory process. A reduction in IL-6 activity has been shown to decrease joint inflammation and some of the systemic effects of rheumatoid arthritis. Presently, no IL-6 receptor is FDA- approved.


Paul Emery, MD, arc professor of rheumatology at the University of Leeds (UK), and associates randomized 499 patients to treatment with placebo, tocilizumab 8 mg/kg, or tocilizumab 4 mg/kg, administered intravenously every four weeks, plus methotrexate, for 24 weeks.


Professor Emery is the principal investigator of the trial, known as Research on Actemra Determining Efficacy after Anti-TNF Failure (RADIATE).


Participants in the trial had active moderate to severe active rheumatoid arthritis and had failed at least one prior TNF antagonist in the last year.


The primary endpoint was the American College of Rheumatology (ACR)20 response at week 24.


Overall, 50 percent of patients in the tocilizumab 8 mg/kg plus methotrexate arm achieved ACR20 versus 10 percent of patients receiving placebo infusions plus weekly methotrexate, p less than 0.0001. Also, 29 percent and 4 percent of the two groups, respectively, achieved ACR50 ( p less than 0.0001) and 12 percent and 1 percent achieved ACR70 (p=0.0002). "A response of ACR50 or greater is considered clinically significant," Professor Emery said.


In addition, 30.1 percent of patients assigned to tocilizumab plus methotrexate achieved Disease Activity Score (DAS)28 less than 2.6, which is indicative of disease remission, versus 1.6 percent of patients assigned to methotrexate as solo therapy.


Tocilizumab was effective regardless of the prior number of anti-TNF therapies and was generally well tolerated "with a safety profile consistent with the agent's mechanism of action and immunomodulatory properties of IL-6 inhibition." Most adverse events were mild or moderate. The most common adverse events with a higher incidence in tocilizumab groups were infections, gastrointestinal symptoms, rash, and headache.


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Professor Emery said that the trial is the first to demonstrate the efficacy of tocilizumab plus methotrexate in patients with an inadequate response to TNF-antagonist treatment.


Rheumatoid arthritis is a chronic, immune-mediated, systemic disease that affects roughly 1% of the population.


Written by Jill Stein

Jill Stein is a Paris-based freelance medical writer.

jillstein03(at)gmail


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