A randomised, double-blind, parallel-group study of the safety and efficacy of subcutaneous tocilizumab versus intravenous tocilizumab in combination with traditional disease-modifying antirheumatic drugs in patients with moderate to severe rheumatoid arthritis (SUMMACTA study)

Abstract

Objectives: This study compared the efficacy and safety of subcutaneous (SC) versus intravenous (IV) formulations of tocilizumab in patients with rheumatoid arthritis with an inadequate response to disease-modifying antirheumatic drugs (DMARD).

Methods: Patients (n=1262) were randomly assigned to receive tocilizumab-SC 162 mg weekly+placebo-IV every 4 weeks or tocilizumab-IV 8 mg/kg every 4 weeks+placebo-SC weekly in combination with traditional DMARD. The primary outcome was to demonstrate the non-inferiority of tocilizumab-SC to tocilizumab-IV with regard to the proportion of patients in each group achieving an American College of Rheumatology (ACR) 20 response at week 24 using a 12% non-inferiority margin (NIM). Secondary outcomes were disease activity score using 28 joints (DAS28), ACR responses, health assessment questionnaire scores and safety assessments.

Results: At week 24, 69.4% (95% CI 65.5 to 73.2) of tocilizumab-SC-treated patients versus 73.4% (95% CI 69.6 to 77.1) of tocilizumab-IV-treated patients achieved an ACR20 response (weighted difference between groups -4.0%, 95% CI -9.2 to 1.2); the 12% NIM was met. ACR50/70 responses, DAS28 and physical function improvements were comparable between the tocilizumab-SC and tocilizumab-IV groups. The safety profiles of tocilizumab-SC and tocilizumab-IV were similar, and the most common adverse event was infection. Injection-site reactions (ISR) occurred more frequently in the tocilizumab-SC group than in the tocilizumab-IV (placebo-SC) group. No anaphylaxis was reported over the 24 weeks.

Conclusions: Tocilizumab-SC 162 mg weekly demonstrated comparable efficacy to tocilizumab-IV 8 mg/kg. The safety profile of tocilizumab-SC is consistent with the known and well-established safety profile of tocilizumab-IV, with the exception of a higher incidence of ISR, which were more common with tocilizumab-SC administration.

Keywords: DMARDs (biologic); Disease Activity; Rheumatoid Arthritis.

Figure 1

Patient disposition over 24 weeks. TCZ-IV, intravenous tocilizumab; TCZ-SC, subcutaneous tocilizumab. AE, adverse events; qw, weekly.

Figure 2

Disease activity and physical function over 24 weeks for patients in the per-protocol (PP) population. (A) Proportion of patients in the PP population treated with either subcutaneous tocilizumab (TCZ-SC; n=558) or intravenous tocilizumab (TCZ-IV; n=537) achieving 20%, 50% and 70% improvements per American College of Rheumatology criteria (ACR20, ACR50 and ACR70) over 24 weeks. (B) Proportion of patients achieving remission based on disease activity score using 28 joints (DAS28) based on erythrocyte sedimentation rate (ESR <2.6) over 24 weeks. (C) Proportion of patients achieving a health assessment questionnaire (HAQ) response (improvement of ≥0.3 from baseline) over 24 weeks. qw, weekly.

Figure 3

Proportion of patients stratified by weight in the per-protocol population treated with either subcutaneous tocilizumab (TCZ-SC; n=558) or intravenous tocilizumab (TCZ-IV; n=537) (A) achieving 20%, 50% and 70% improvements per American College of Rheumatology criteria (ACR20, ACR50 and ACR70) over 24 weeks and (B) achieving remission based on disease activity score using 28 joints (DAS28) based on erythrocyte sedimentation rate (ESR <2.6) over 24 weeks. qw, weekly.