For patients with rheumatoid arthritis (RA) with insufficient response to methotrexate, adding sarilumab to methotrexate treatment can significantly improve symptoms and physical function, according to a study published in Arthritis Research & Therapy.
The investigators of this randomized, parallel-group study sought to assess the efficacy and safety of sarilumab in combination with methotrexate to treat patients with active RA who had an inadequate response to methotrexate monotherapy.
The study included 243 Japanese patients who were randomly selected to receive subcutaneous sarilumab 150 mg every 2 weeks (n=81), sarilumab 200 mg every 2 weeks (n=80), placebo followed by sarilumab 150 mg at 24 weeks (n=42), or placebo followed by sarilumab 200 mg at 24 weeks (n=40); all patients received methotrexate as background therapy. Participants were followed for a total of 52 weeks, including a double-blind, placebo-controlled 24-week study period followed by a single-blind 28-week extension period.
The primary study outcome was the proportion of patients achieving 20% improvement in American College of Rheumatology criteria (ACR20) at 24 weeks. Safety assessments were captured by adverse events, vital signs, laboratory values, physical examination, and electrocardiogram results.
At 24 weeks, the ACR20 response rates among study groups were 67.9% for the sarilumab 150 mg group, 57.5% for the sarilumab 200 mg group, and 14.8% for placebo (the 2 placebo groups were combined in week 24 analyses). At 52 weeks, ACR20 response rates were maintained by sarilumab plus methotrexate, with 71.6% and 60.0% for sarilumab 150 mg and sarilumab 200 mg, respectively. For placebo groups that switched to sarilumab, ACR20 response rates at 52 weeks were 64.3% for sarilumab 150 mg and 66.7% for sarilumab 200 mg.
Serious treatment-emergent adverse events were reported in 9.9% of the sarilumab 150 mg group, 6.3% of the sarilumab 200 mg group, 0% of the placebo to the sarilumab 150 mg group, and 13.3% of the placebo to the sarilumab 200 mg group. Overall, infections were the most common treatment-emergent adverse events with incidence of infections ranging from 52.5% to 67.9% among treatment groups. However, serious infections were only reported by 5 participants in the sarilumab 150 mg group and 1 participant in the placebo to sarilumab 200 mg group; no deaths were reported. While an abnormal absolute neutrophil count <1.0 Giga/l was reported in 13.6% of the sarilumab 150 mg group and 7.5% of the sarilumab 200 mg group, neutropenia was generally not associated with risk for infection.
A limitation to the study was the use of a Japanese population that suffered from long-term RA and who had been previously treated with biologic disease-modifying antirheumatic drugs (DMARDs), preventing the generalizability of findings to other populations, patients with new-onset RA, or patients characterized by inadequate response to biologic DMARDs. In addition, lack of measurements of radiographic disease progression may have limited the study results.
Patients with RA with inadequate response to methotrexate showed significant improvement when treated with sarilumab plus methotrexate, with clinical efficacy sustained through 52 weeks of treatment. The safety profiles of both sarilumab doses plus methotrexate were generally similar and consistent with the primary analysis.
This study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc.
Tanaka Y, Wada K, Takahashi Y, et al. Sarilumab plus methotrexate in patients with active rheumatoid arthritis and inadequate response to methotrexate: results of a randomized, placebo-controlled phase III trial in Japan [published online March 20, 2019]. Arthritis Res Ther. doi: 10.1186/s13075-019-1856-4