PARIS, France—Tocilizumab (Actemra^®) combined with methotrexate shows efficacy for treating rheumatoid arthritis (RA) patients who have responded inadequately to anti-tumor necrosis factor (anti-TNF) therapy, according to phase III results released at the 2008 European Union League Against Rheumatism.

“The results are dramatic considering that nearly 20% of patients had failed to respond to three or more prior anti-TNF therapies, [which] are considered the best option presently available,” Paul Emery, MD, professor of rheumatology at the University of Leeds in the UK, pointed out at a news conference. Dr. Emery is the principal investigator of the trial, known as Research on Actemra Determining Efficacy after Anti-TNF Failure (RADIATE). The RADIATE trial was conducted at 128 sites in 13 countries.

50% of patients achieve ACR20 with tocilizumab/MTX after TNF-inhibitor failure

The investigators randomized 499 patients to MTX plus placebo, MTX plus tocilizumab 8 mg/kg, or tocilizumab 4mg/kg administered intravenously every 4 weeks for 24 weeks. Trial participants had moderate-to-severe RA and had failed prior anti-TNF treatment. The primary endpoint was the percentage of patients who achieved American College of Rheumatology (ACR) 20 response.

Overall, 50% of patients in the tocilizumab 8 mg/kg plus MTX arm achieved ACR20 versus 10% who received placebo infusions plus weekly MTX (P <.0001). Also, 29% and 4% of the two groups, respectively, achieved ACR50 (P <.0001); 12% and 1%, respectively, achieved ACR70 (P = .0002).

“A response of ACR50 or greater is considered clinically significant,” Dr. Emery said. He reported that 30.1% of patients assigned to tocilizumab plus MTX achieved Disease Activity Score 28 <2.6, indicating disease remission, versus 1.6% assigned to MTX monotherapy.

Tocilizumab was effective regardless of the number of prior anti-TNF therapies, and it was generally well tolerated “with a safety profile consistent with the agent’s mechanism of action and immunomodulatory properties of IL (interleukin)-6 inhibition,” said Dr. Emery. The agent was, however, associated with an increase in lipids, the significance of which is unclear, he added.

The results show the efficacy of switching RA patients who respond inadequately to anti-TNF therapy to tocilizumab plus MTX, he concluded. Tocilizumab is a monoclonal antibody that inhibits the human IL- 6 receptor, a key cytokine in the inflammatory process.

Reference

1. Emery P, Keystone E, Tony H, et al. Tocilizumab (TCZ) significantly improves disease outcomes in patients with rheumatoid arthritis whose anti-TNF therapy failed: the RADIATE study. Presented at: EULAR 2008; June 11-14, 2008; Paris, France. Presentation OP-0251.