Two studies show IL-6 receptor inhibitor improves RA symptoms in disease-modifying drug non-responders

Significantly more tocilizumab-treated patients in the TOWARD and OPTION trials achieved 20% reductions in symptoms compared to controls.

Data from two pivotal, multinational phase 3 clinical trials presented at the American College of Rheumatology annual scientific meeting show that an IL-6 receptor inhibiting drug significantly improved the signs and symptoms of rheumatoid arthritis in patients who failed to adequately respond to other disease modifying antirheumatic drugs, according to a press release from Roche.

Mark C. Genovese, MD, an associate professor of medicine at Stanford University School of Medicine in Stanford, Calif., presented data from the TOWARD (Tocilizumab in Combination With traditional DMARD therapy) trial.

"We are very encouraged by the findings of this new TOWARD data, which suggest Actemra (tocilizumab, Roche) plus DMARDs (disease modifying antirheumatic drugs) demonstrates significant improvement in RA (rheumatoid arthritis) symptoms compared with DMARDs alone," Genovese, lead investigator in the trial, said in the release.

Josef Smolen, MD, a professor of medicine at the University Clinic for Internal Medicine in Vienna, Austria, also presented data from the OPTION (Tocilizumab Pivotal Trial in Methotrexate Inadequate Responders) study.

'A novel method'

"The data from both studies further establish the efficacy of Actemra and confirm that inhibiting interleukin-6 (IL-6) receptor is a novel method of reducing RA symptoms," Genovese said.

Data from the two studies showed that more than half of patients in the groups treated with tocilizumab plus DMARD therapies experienced at least a 20% reduction in RA symptoms compared to those treated with placebo plus DMARD therapies.

In the TOWARD trial, 61% of patients treated with tocilizumab plus DMARDs achieved a 20% reduction in RA symptoms compared to 25% of patients who received placebo (P<.0001) at 24 weeks follow-up. In addition, within 2 weeks, patients treated with tocilizumab showed a measurably higher American College of Rheumatology-20 (ACR20) response compared to controls.

Also at 24 weeks follow-up, 59% of patients in the OPTION trial who were treated with 8 mg/kg of tocilizumab plus methotrexate experienced a 20% reduction in symptoms vs. 27% of patients in the placebo arm (P<.0001), according to the release.

Tocilizumab was generally well tolerated in both studies. The most common adverse events reported in the tocilizumab arm included upper respiratory tract infections, headache, nasopharyngitis and hypertension, the release reported.

Multicenter trials

The TOWARD trial is a two-arm, double-blind, placebo-controlled study evaluating the safety and efficacy of tocilizumab plus DMARDs compared to placebo plus DMARDs. Patients were randomly assigned to receive either tocilizumab intravenously at 8 mg/kg every 4 weeks plus DMARDs weekly or placebo infusions plus DMARDs weekly. The study included 1,216 patients treated at 130 sites in 18 countries.

The OPTION trial involved 623 patients randomly assigned to receive either tocilizumab intravenously — 4 mg/kg or 8 mg/kg — every 4 weeks plus methotrexate weekly or placebo infusions plus methotrexate weekly. The study was conducted at 73 sites in 17 countries outside the United States.

Both the TOWARD and OPTION studies showed that, at 24 weeks follow-up, significantly more tocilizumab-treated patients achieved a 20% (ACR20), 50% (ACR50) and 70% (ACR70) reduction in symptoms compared to controls.

In both studies, levels of C-reactive protein showed an improvement within 2 weeks and remained at normal levels through to final follow-up. Patients treated with tocilizumab plus DMARDs also experienced greater improvements in quality of life and function measures, including fatigue, physical and mental functions, compared to placebo plus DMARDs, the release noted.

For more information:
Genovese M, McKay J, Nasonov E, et al. IL-6 receptor inhibition with tocilizumab reduces disease activity in patients with rheumatoid arthritis with inadequate response to a range of DMARDs: The TOWARD study. #L15. Presented at the American College of Rheumatology Annual Scientific Meeting. Nov. 6-11, 2007. Boston.
Smolen J, Rovensky J, Ramos-Remus C, et al. Targeting the IL-6 receptor with the monoclonal antibody tocilizumab significantly improves quality of life in patients with rheumatoid arthritis. #292. Presented at the American College of Rheumatology Annual Scientific Meeting. Nov. 6-11, 2007. Boston.