Source: DGNews  |  Posted 4 years ago

By Ed Susman

BOSTON, MA -- November 12, 2007 -- Doctors said that a new drug that targets the interleukin-6 (IL-6) receptor appears to provide rapid and sustained relief to rheumatoid arthritis patients whose condition has progressed while taking methotrexate, the standard first-line treatment.

The researchers presented their findings here in a press briefing November 10 at the 71st annual meeting of the American College of Rheumatology (ACR).

"With the 8-mg/kg dose of tocilizumab about 58.5% of our patients achieved the primary endpoint of ACR20," said Josef Smolen, MD, Professor of Medicine, Medical University of Vienna and Hietzing Hospital, Vienna, Austria. Only 26.5% of patients on placebo achieved an ACR20. The difference between the groups reached statistical significance at the P <.0001 level, Dr. Smolen added.

ACR20 represents a 20% improvement according to ACR criteria in tender joint counts, a 20% improvement in swollen joint counts, and at least a 20% improvement in at least three of five of the following: the patient's pain assessment, the patient's global assessment, the physician's global assessment, the patient's self-addressed disability, and the acute phase reactant - the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). ACR50 and ACR70 indicate further improvements in the same manner.

Dr. Smolen explained that scientists sought to inhibit IL-6 because the cytokine plays a fundamental role in the inflammation cascade that drives rheumatoid arthritis.

"The efficacy of IL-6 receptor inhibition with tocilizumab confirms the critical role of IL-6 in the pathophysiology of rheumatoid arthritis," he said.

Dr. Smolen and colleagues recruited 623 patients with rheumatoid arthritis who had progressed while taking methotrexate. They were assigned to 3 different treatment groups with 204 patients adding placebo to their regimen in the 6-month, phase 3 clinical trial. Another 214 patients were assigned to 4 mg/kg of tocilizumab; and a group of 205 patients were assigned to receive 8 mg/kg of tocilizumab.

Patients were eligible for the Tocilizumab Pivotal Trial in Methotrexate Inadequate Responders (OPTION) study if they had moderate to severe rheumatoid arthritis for at least 6 months, had been on methotrexate for at least 12 weeks, and had been on a stable dose of methotrexate for 8 weeks. Patients were excluded if they had been unsuccessfully treated previously with an antitumor necrosis factor agent.

Dr. Smolen said the main results of the study showed that 58.5% of patients on the high dose of tocilizumab achieved the ACR20 compared with 47.9% of patients on the lower dose and compared with 26.5% of patients on placebo.

He added that 43.9% of patients on the higher dose of tocilizumab and 31.5% of patients on the lower dose of tocilizumab achieved an ACR50 compared with 10.8% of placebo patients.

He reported that 22.8% of patients on the high dose of tocilizumab and 12.2% of patients on the lower dose of tocilizumab achieved ACR70 responses compared with 2% of placebo patients. All the differences between the active agent and placebo were significant at P <.0001, he said.

The improvement in the patients' condition came with little cost in adverse events, Dr. Smolen said. The serious adverse event rate was similar between placebo and the tocilizumab groups. About 2.5% of placebo patients discontinued the drug due to adverse events compared with 6.5% of the low-dose tocilizumab patients and 6.3 % of the patients on the higher dose.

The trial was sponsored by F. Hoffman LaRoche.

[Presentation title: Targeted Inhibition of the IL-6 Receptor With Tocilizumab Effectively Reduces Disease Activity in Patients With Rheumatoid Arthritis. Abstract 2089]