Phase III Study of the Efficacy and Safety of Subcutaneous Versus Intravenous Tocilizumab Monotherapy in Patients With Rheumatoid Arthritis

Abstract

Objective: To evaluate the efficacious noninferiority of subcutaneous tocilizumab injection (TCZ‐SC) monotherapy to intravenous TCZ infusion (TCZ‐IV) monotherapy in Japanese patients with rheumatoid arthritis (RA) with an inadequate response to synthetic and/or biologic disease‐modifying antirheumatic drugs (DMARDs). Methods: This study had a double‐blind, parallel‐group, double‐dummy, comparative phase III design. Patients were randomized to receive TCZ‐SC 162 mg every 2 weeks or TCZ‐IV 8 mg/kg every 4 weeks; no DMARDs were allowed during the study. The primary end point was to evaluate the noninferiority of TCZ‐SC to TCZ‐IV regarding the American College of Rheumatology criteria for 20% improvement in disease activity (ACR20) response rates at week 24 using an 18% noninferiority margin. Additional efficacy, safety, pharmacokinetic, and immunogenicity parameters were assessed. Results: At week 24, ACR20 response was achieved in 79.2% (95% confidence interval [95% CI] 72.9, 85.5) of the TCZ‐SC group and in 88.5% (95% CI 83.4, 93.5) of the TCZ‐IV group; the weighted difference was −9.4% (95% CI −17.6, −1.2), confirming the noninferiority of TCZ‐SC to TCZ‐IV. Remission rates of the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate and the Clinical Disease Activity Index at week 24 were 49.7% and 16.4% in the TCZ‐SC group and 62.2% and 23.1% in the TCZ‐IV group, respectively. Serum trough TCZ concentrations were similar between the groups over time. Incidences of all adverse events and serious adverse events were 89.0% and 7.5% in the TCZ‐SC group and 90.8% and 5.8% in the TCZ‐IV group, respectively. Anti‐TCZ antibodies were detected in 3.5% of the TCZ‐SC group; no serious hypersensitivity was reported in these patients. Conclusion: TCZ‐SC monotherapy demonstrated comparable efficacy and safety to TCZ‐IV monotherapy. TCZ‐SC could provide additional treatment options for patients with RA.