Background/Purpose: The objective of this study was to compare the efficacy and safety of tocilizumab (TCZ) subcutaneous (SC) and TCZ intravenous (IV) regimen in patients with adult rheumatoid arthritis (RA) who had an inadequate response to DMARDs (up to 20% may have failed one or more anti-TNF agents).

Methods: This 2-year Phase 3 trial is a randomized, active controlled, parallel group, study including a 24-week double-blind (DB) period, followed by a 72-week open-label phase. TCZ SC dose was based on previous pharmacological studies. During the DB period, patients (pts) received TCZ SC 162 mg qw + placebo IV q4w or TCZ IV 8mg/kg q4w + placebo SC qw, in combination with traditional DMARDs. The primary end point to demonstrate the non-inferiority of TCZ SC to TCZ IV was the proportion of patients in each group meeting the ACR20 improvement criteria at Week 24.  Additional clinical efficacy, immunogenicity and safety assessments were evaluated as secondary outcomes. Pts were stratified by body weight and regions at baseline. The hypothesis of non-inferiority of TCZ SC with respect to TCZ IV regarding ACR20 response was tested by means of 95% confidence interval (CI) and with a 12% non-inferiority margin (NIM).

Results: A total of 1262 pts were enrolled globally.  Mean baseline characteristics were similar between TCZ SC and TCZ IV groups: age 53 years; RA duration 9 years; DAS28-ESR 6.6 and 6.7, respectively. At Week 24, 69.4% (95% CI: 65.5, 73.2) of TCZ SC-treated pts versus 73.4% (95% CI: 69.6, 77.1) of TCZ IV-treated pts achieved an ACR20 response (weighted difference between groups 4.0% [95% CI: -9.2, 1.2]); a 12% NIM was met.  ACR50/70 responses, disease activity and physical function improvements were also comparable between TCZ SC and TCZ IV groups. Up to Week 24, the proportions of pts with at least one adverse event (AE) and serious AE were 76.2% and 4.6%, respectively in the TCZ SC group compared with 77.0% and 5.2%, respectively in the TCZ IV group.  The most common AEs in both groups were infections. Injection site reactions occurred more frequently in the TCZ SC (placebo IV) group than the TCZ IV (placebo SC) group (10.1% vs 2.3%, respectively); most were grade 1 severity. No anaphylaxis was reported over the 24-week period. 

Conclusion: TCZ SC 162mg qw demonstrated comparable efficacy and safety to TCZ IV 8mg/kg q4w. No new clinically meaningful safety signals were identified in TCZ SC-treated pts.