BOSTON, Massachusetts—The interleukin-6 (IL-6) blocker tocilizumab is safe, effective, and improves quality of life for rheumatoid arthritis (RA) patients, according to two new phase III studies presented at the annual meeting of the American College of Rheumatology in Boston.^1,2

"Tocilizumab is effective and it has an ability to rapidly improve function and quality of life in patients who have tried and failed a host of conventional DMARDs, and it can be given with a host of conventional DMARDs as background," Mark C. Genovese, MD, associate professor of medicine at Stanford University School of Medicine in Palo Alto, California, told MSKReport.com. Dr. Genovese is an author on the quality of life study.

Il-6 blockade is safe and effective

In a phase III trial, 623 RA patients received 8 mg/kg of tocilizumab, 4 mg/kg of tocilizumab, or placebo intravenously every four weeks for 6 months. All participants received weekly doses of methotrexate (MTX) throughout the study. No other disease-modifying antirheumatic drugs (DMARDS) were allowed.

A significantly higher proportion of patients treated with tocilizumab achieved ACR20 by 24 weeks. Specifically, 59% of patients in the high-dose group achieved an ACR20 response as did 48% of those taking the 4 mg/kg dose. By contrast, 27% of patients randomized to placebo achieved the ACR20 response (P<.0001). Significantly more patients taking the experimental IL-6 blocker also achieved ACR50 and ACR70 responses by 24 weeks. Forty-four percent of patients receiving 8 mg/kg and 32% receiving 4 mg/kg achieved an ACR50 response at 24 weeks, compared with 11% of RA patients who received placebo. In addition, 22% of patients who received the 8 mg/kg dose of tocilizumab achieved an ACR70 response, compared with 2% of those randomized to placebo.

A total of 21 tocilizumab-treated patients achieved an ACR90 response, including 11 (5.4%) in the 8 mg/kg group and 10 (4.7%) in the 4 mg/kg group. None of the patients who received placebo achieved the ACR90 response. C-reactive protein levels normalized by 2 weeks' treatment in the 8 mg/kg group and remained normal to study end.

The new drug appeared to be safe. There were 41 serious adverse events affecting approximately 6% of participants in each group; 15 were considered related to the study treatment and 11 led to discontinuation of treatment. Serious infections were observed more often in the participants treated with tocilizumab than placebo.

"IL-6 is one of the important targets that interferes with the activity of RA," lead researcher Josef Smolen, MD, professor of medicine and chairman of the department of internal medicine III and division of rheumatology at the Medical University of Vienna and chairman of the second department of medicine at Hietzing Hospital in Vienna, Austria, told MSKReport.com.

Exactly what role tocilizumab will have in the treatment of RA is not clear. "At the present time studies have not been done in TNF failures, but rather in MTX failures," he said. "In principle, I am optimistic. I think it's good to have more options for our patients."

Tocilizumab improves quality of life

In a second phase III study of 1216 patients, patients who received tocilizumab showed early significant and clinically relevant improvement in all quality of life parameters as measured by Health Assessment Questionnaire (HAQ), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale, and the Short Form 36 health survey (SF-36). Participants continued stable preentry doses of methotrexate, chloroquine/hydroxychloroquine, sulfasalazine, leflunomide, azathioprine, or parenteral gold and received additional tocilizumab at 8 mg/kg or placebo intravenously every 4 weeks for 6 months.

Tocilizumab-treated patients showed improvements in their HAQ scores at 24 weeks, compared with their counterparts who received placebo infusions, -0.47 versus -0.20, respectively (P <.0001). Improvement in HAQ-Disability Index scores were seen as early as 2 weeks in the tocilizumab-treated patients, the study showed.

Fully 60.4% of patients receiving tocilizumab and 33.9% of patients receiving placebo achieved a clinically relevant improvement in FACIT-Fatigue scores. Improvements in fatigue were seen as early as week 8 in the tocilizumab arm. Tocilizumab-treated patients also showed greater improvements in SF-36 physical and mental component scores compared with their counterparts who received placebo.

What's more, these improvements in quality of life also correlated with reduction in disease activity among patients taking the study drug. "Tocilizumab is an effective biologic agent for RA with significant improvement in symptoms and signs, quality of life, and function," said Dr. Genovese. He told MSKReport.com that there will be "significant X-ray data" coming soon.

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