Novel IL-6 Inhibitor Proves Mettle in RA

Huizinga TW, Fleischmann RM, Jasson M, et al.. Sarilumab, a fully human monoclonal antibody against IL-6Rα in patients with rheumatoid arthritis and an inadequate response to methotrexate: efficacy and safety results from the randomised SARIL-RA-MOBILITY Part A trial. Ann Rheum Dis. (2013) doi: 10.1136/annrheumdis-2013-203915. Published online ahead of print.

Sarilumab, a new interleukin-6 receptor inhibitor, signficantly improves signs and symptoms of moderate-to-severe rheumatoid arthritis (RA) over 12 weeks, according to results of a randomized, placebo-controlled trial.

The phase II, multicenter trial assigned more than 300 patients to one of six dosing regimens of sarilumab or placebo, both with stable methotrexate. The trialists reported that two doses in particular -- 150 mg and 200 mg injected subcutaneously every 2 weeks --  were both optimal and convenient.

Giving the two optimal doses produced a 20% improvement in the American College of Rheumatology (ACR20) response criteria of swollen and tender joints in greater proportions of patients (65% and 67%) than did placebo.

The highest dose (150 mg weekly) produced an ACR20 response in 72% of the  patients, the majority of whom were white and female with a median age of 52.

The lowest dose (100 mg biweekly) was ineffective.

All but one dosing regimen improved ACR50 and ACR70 criteria and induced remission, defined as scores of less than 2.6 points in the 28-joint disease activity/C-reactive protein scores.

Although many patients in the six sarilumab groups (43%-72%) experienced adverse events related to treatment -- mostly infections and neutropenia -- only 24 patients discontinued treatment.

Sarilumab had a safety profile similar to that of the more=established IL-6 inhibitor tocilizumab.

The 150-mg and 200-mg doses of sarilumab are now being tested in a phase III trial.