Patients with active rheumatoid arthritis (RA) and inadequate response to methotrexate (MTX-IR) could have positive clinical outcomes with sarilumab plus MTX, according to a recent study in a Japanese population.
“Sarilumab is a human immunoglobulin G1 anti-interleukin-6 (IL-6) receptor monoclonal antibody that blocks IL-6 from binding to membrane-bound and soluble IL-6 receptor α,” the study authors wrote. “This bridging study assessed the efficacy and safety of sarilumab + methotrexate (MTX) in Japanese patients with active rheumatoid arthritis (RA) and inadequate response to MTX (MTX-IR).”
For the trial, eligible patients had to be aged between 20 and 75 years and have moderately to severely active disease, defined as ≥ eight of 68 tender joints and ≥ six of 66 swollen joints, and high-sensitivity CRP ≥ 0.6 mg/dL. MTX-IR was defined as ≥ three months’ disease duration despite continuous six-week MTX treatment at least six weeks prior to screening. Patients with uncontrolled concomitant disease, severe systemic RA, other autoimmune or inflammatory systemic or localized joint diseases, current/recurrent infections, or past history of nonresponse to prior therapy with a TNF antagonist or a biologic treatment were not included in the trial.
A total of 243 patients were randomized 2:2:1:1 to one of the following treatment options, in combination with MTX: subcutaneous sarilumab 150 mg every 2 weeks (q2w), sarilumab 200 mg q2w, placebo switching to sarilumab 150 mg q2w + MTX at 24 weeks, or placebo switching to sarilumab 200 mg q2w at 24 weeks. The study’s primary endpoint was how many patients successfully attained 24-week American College of Rheumatology 20% improvement criteria (ACR20).
Sarilumab plus methotrexate in patients with active rheumatoid arthritis and inadequate response to methotrexate results of a randomized placebocontrolled phase III trial in Japan: Sarilumab is a human immunoglobulin G1 antiinterleukin6 IL6 receptor… https://t.co/PF1K6fuspv
— Antibody News (@AntibodyNews) March 21, 2019
Sarilumab Outperforms Placebo
After 24 weeks, the proportion of patients who achieved ACR20 response rates were as follows: sarilumab 150 mg, 67.9%; sarilumab 200 mg, 57.5%; and placebo, 14.8%. No deaths occurred, and placebo to sarilumab 150 mg group experienced no adverse effects; in the other groups, adverse events rates were 9.9% in the sarilumab 150 mg group, 6.3% in the sarilumab 200 mg group, and 13.3% in the placebo to sarilumab 200 mg group. Infection incidence ranged from 52.5% to 67.9%. The sarilumab 150 mg group had five serious infections, while the placebo to 200 mg sarilumab group had one. There was no association between absolute neutrophil count < 1.0 Giga/l and infection, which presented in 13.6% of the sarilumab 150 mg group and 7.5% of the sarilumab 200 mg group.
The study authors concluded, “Despite the availability of a wide range of treatment options for RA, there remains an unmet need globally for the treatment of patients who are intolerant or refractory to current therapies. These important findings show that a new treatment option that has been assessed globally is also effective for Japanese patients with RA.”
Open Access UCL Research: Evaluation of the efficacy and safety of sarilumab combination therapy in patients with rheumatoid arthritis with inadequate response to conventional disease-modifying antirheumatic drugs or tumour necrosis factor α inhibitors https://t.co/XbZwBZzuer
— UCL Discovery (@ucl_discovery) March 21, 2019