Novel Rheumatoid Arthritis Drug Shows Improvement in Symptoms

Treatment with sarilumab improves RA signs, symptoms, and physical function.

An experimental treatment for rheumatoid arthritis (RA) showed promising results during a recent phase 3 clinical trial.

Sarilumab is an investigational human antibody that acts against the IL-6 receptor. The drug, in development by Regeneron and Sanofi, met both co-primary endpoints by improving the signs and symptoms of RA, in addition to improving physical function.

"Rheumatoid arthritis can be a debilitating disease that has a significant impact on a patient, and despite the availability of a wide range of treatments, new agents are still needed to address unmet patient needs including failure to respond to therapy," said lead author Dr. Roy Fleischmann, clinical professor in the Department of Internal Medicine at the University of Texas Southwestern Medical Center. "These data suggest that sarilumab, if approved, may be a potential option for patients with moderate-to-severe RA."

Sarilumab binds with high affinity to the IL-6 receptor to block IL-6 from binding to its receptor while inhibiting the subsequent cytokine-mediated inflammatory signaling.

The trial randomized 546 patients with RA who had an inadequate response or were intolerant of TNF-alpha inhibitors into 3 treatment groups.

The patients self-administered subcutaneously every other week either sarilumab 200 mg, sarilumab 150 mg, or placebo. Each patient group also received non-biologic disease modifying anti-rheumatic drugs (DMARD).

The sarilumab treatment arms both achieved clinically relevant and statistically significant improvements compared with placebo in both of the study’s primary endpoints.

Firstly, patients showed improvements in physical function at week 12 as measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI), which measures the abilities of patients to perform a standard set of daily physical activities.

The HAQ-DI score changes from baseline to week 12 were -0.49, -0.50, and -0.29 in the sarilumab 200 mg (p=0.0004) group, sarilumab 150 mg (p=0.0007) group, and placebo group, respectively.

Secondly, improvements in RA signs and symptoms at week 24 determined by the proportion of patients achieving an ACR20 response were 61% in the sarilumab 200 mg group; 56% in the sarilumab 150 mg group; and 34% in the placebo group, all of which were combined with DMARD treatment (p less than 0.0001).

Adverse events occurred more frequently in the sarilumab treatment groups, at 65% and 66% in the sarilumab 200 mg and 150 mg cohorts, respectively, compared with 50% in the placebo cohort.

Serious adverse events occurred in 5% of the sarilumab 200 mg group compared with 3% in both the 150 mg and placebo groups.

The most serious adverse event was infection, which occurred in 30%, 22% and 27% in the 200 mg, 150 mg, and placebo groups respectively. The most frequent adverse events that led to discontinuation of treatment were infection and neutropenia.