Background/Purpose: The non-inferiority of subcutaneous tocilizumab (TCZ-SC) monotherapy every 2 weeks (q2w) to intravenous TCZ monotherapy every 4 weeks was demonstrated in Japanese patients with rheumatoid arthritis (RA).¹ During the open-label period, patients with an inadequate response to TCZ-SC q2w could shorten the dosing interval to receive TCZ-SC weekly (qw), which resulted in improved efficacy.² To confirm this preliminary result, the objective of this study was to determine the efficacy and safety of TCZ-SC qw vs TCZ-SC q2w in patients with RA who had an inadequate response to TCZ-SC q2w.

Methods: Adult RA patients with Disease Activity Index 28-joints based on erythrocyte sedimentation rate (DAS28-ESR) > 3.2, tender joint count (TJC) using 66 joints and swollen joint count (SJC) using 68 joints ≥ 4 each, and C-reactive protein (CRP) ≥ 0.3 mg/dL within 2 weeks of their last TCZ-SC dose, despite ≥ 8 weeks of TCZ-SC q2w therapy, were included. Patients were randomized 1:1 to receive either TCZ-SC 162 mg qw as monotherapy or TCZ-SC 162 mg q2w as monotherapy (double-blind period). After 12 weeks, all patients received TCZ-SC qw for 40 weeks (open-label period). The primary endpoint was the change from baseline in DAS28-ESR at week 12 using analysis of covariance (ANCOVA), adjusted by DAS28-ESR at randomization. The aim of this study was to demonstrate the superiority of TCZ-SC qw to TCZ-SC q2w. Additional efficacy, safety and pharmacokinetic parameters were assessed.

Results: Of the 43 patients enrolled, 21 received TCZ-SC qw and 21 received TCZ-SC q2w. TCZ-SC qw was superior to TCZ-SC q2w for adjusted mean change in DAS28-ESR from baseline to week 12 (−2.10 vs −0.89; P = 0.0108 [Table]). The adjusted mean change in Clinical Disease Activity Index from baseline to week 12 was −16.0 in the TCZ-SC qw group and −8.7 in the TCZ-SC q2w group (P = 0.0979; as per hierarchical testing). The proportions of patients who achieved DAS28-ESR remission or low disease activity were 42.9% and 25.0% for the TCZ-SC qw and TCZ-SC q2w groups, respectively. Improvements in TJC, SJC, CRP and ESR, and the proportion of patients achieving ACR20/50, were greater in the TCZ-SC qw group than the TCZ-SC q2w group. The proportions of patients who experienced adverse events (AE) were 71.4% and 66.7% in the TCZ-SC qw and TCZ-SC q2w groups, respectively. One patient in each group experienced ≥ 1 serious AE. There was 1 death in the TCZ-SC qw group.

Conclusion: In patients with an inadequate response to TCZ-SC q2w, TCZ-SC qw was superior to TCZ-SC q2w for improving DAS28-ESR at 12 weeks. The safety profile was comparable between patients who received TCZ-SC qw or TCZ-SC q2w, and was consistent with the safety profile of TCZ from previous studies. This study suggests that in patients with an inadequate response to TCZ-SC q2w, shortening the dosing interval to TCZ-SC qw is an effective treatment option.

1. Ogata A, et al. Arthritis Care & Res. 2014;66:344-354.

2. Ogata A, et al. J Rheumatol. 2015;42:799-809.