IL-6 inhibitors sarilumab, an investigational drug, and tocilizumab, an established treatment in RA, are equally safe, shows two studies presented at ACR/ARHP 2015.
Sarilumab, an investigational human monoclonal antibody, and tocilizumab, a humanized monoclonal antibody approved for treatment of moderate-to-severe rheumatoid arthritis, appear to have similar safety and tolerability profiles in rheumatoid arthritis, according to results from two studies presented on Nov. 8 at the 2015 ACR/ARHP annual meeting in San Francisco, Calif.
The presentation was based on the results of two studies, Study 1309 and ASCERTAIN. Study 1309 tested single doses of open-label sarilumab and tocilizumab in 101 patients with rheumatoid arthritis throughout the course of six weeks. The patients, who were also prescribed methotrexate, were randomized 1:1:1:1 to sarilumab (150 or 200 mg of sarilumab subcutaneously with methotrexate) or tocilizumab (4mg/kg or 8 mg/kg IV with methotrexate).
In ASCERTAIN, 202 rheumatoid arthritis patients with inadequate response or intolerance to anti-TNF therapy were randomized in a double-blind, double-dummy 1:1:2 to sarilumab 150 or 200 mg SC Q2W with csDMARDs, or tocilizumab 4 mg/kg IV Q4W with csDMARDs. In the tocilizumab group, 61% (n=62) increased their dose to 8 mg/kg at least once.
While there were more injection site reactions with sarilumab and a little more nausea with tocilizumab, there were no meaningful differences in adverse events between sarilumab and tocilizumab groups, according to Paul Emery, M.D., University of Leeds in England, the author of the presentation.
Sarilumab and methotrexate are directed against the IL-6 receptor.
“What is interesting is the insight we gained into blocking the IL-6 receptor,” Dr. Emery said.
The magnitude and timing of decreased absolute neutrophil counts (ANC) were similar for sarilumab and tocilizumab in Study 1309, and the mean changes were in a similar range for the two agents in ASCERTAIN. Incidence of neutrophils dropping to <1.0 Giga/L was somewhat greater for sarilumab in ASCERTAIN.
“Dosing intervals, however, were a factor,” Dr. Emery said. While sarilumab was dosed every two weeks and levels were smoother over time, tocilizumab was dosed every four weeks and neutrophil levels were almost back to normal before the next dose. “Fortunately, infections did not appear to be associated with decreased ANC,” he said.
In prior studies, sarilumab and methotrexate were generally well tolerated in moderate-to-severe rheumatoid arthritis.
“Safety and Tolerability of Subcutaneous Sarilumab Compared to Intravenous Tocilizumab in Patients with RA,” Paul Emery, Nov. 9, 2015. ACR/ARHP 2015, Abstract 971.