Subcutaneous tocilizumab versus placebo in combination with disease-modifying antirheumatic drugs in patients with rheumatoid arthritis

Abstract

Objective: The efficacy and safety of subcutaneous tocilizumab (TCZ-SC) versus subcutaneous placebo (PBO-SC) was evaluated in patients with rheumatoid arthritis who had an inadequate response to disease-modifying antirheumatic drugs in the BREVACTA study.

Methods: Patients (n = 656) were randomized 2:1 to receive TCZ-SC 162 mg every other week or PBO-SC every other week for 24 weeks; 20% previously received anti-tumor necrosis factor treatment. Escape therapy with TCZ-SC 162 mg weekly was offered from week 12 for inadequate response. The primary end point was the American College of Rheumatology 20% improvement (ACR20) response at week 24. The key secondary outcomes were radiographic progression and safety.

Results: TCZ-SC was superior to PBO-SC for ACR20 response at week 24 (60.9% versus 31.5%; P < 0.0001). All secondary end points showed TCZ-SC to be superior to PBO-SC, including ACR50 and ACR70 response (40% and 20% for TCZ-SC, respectively, and 12% and 5% for PBO-SC, respectively; P < 0.0001 for both) and Disease Activity Score in 28 joints (DAS28) remission (DAS28 <2.6; 32% versus 4% [P < 0.0001]). The mean change in modified Sharp/van der Heijde score was significantly lower in the TCZ-SC group than the PBO-SC group (0.62 versus 1.23; P = 0.0149). Adverse events (AEs) and serious AEs (SAEs) were comparable between the TCZ-SC and PBO-SC groups; 4.6% and 3.7% of patients had at least 1 SAE, respectively, and infection was the most common SAE in 2.1% and 1.8% of patients, respectively. More injection site reactions occurred with TCZ-SC than PBO-SC (7.1% versus 4.1%). No anaphylaxis or serious hypersensitivity reactions occurred. There were 3 deaths in the TCZ-SC group and 0 in the PBO-SC group.

Conclusion: TCZ-SC every other week had significantly greater efficacy, including ACR end points and inhibition of joint damage, compared with PBO-SC. TCZ-SC was well tolerated and its safety profile was comparable with that of previous intravenous TCZ studies.

Trial registration: ClinicalTrials.gov NCT01232569.

Figure 1

Patient disposition over 24 weeks. TCZ-SC = subcutaneous tocilizumab; q2w = every other week; DMARDs = disease-modifying antirheumatic drugs; PBO-SC = subcutaneous placebo.

Figure 2

Disease activity, physical function, and radiographic outcomes at 24 weeks for patients in the intent-to-treat population. A, The proportion of patients treated with either subcutaneous tocilizumab (TCZ-SC; n = 437) or placebo (PBO-SC; n = 219) every other week (q2w) who achieved the American College of Rheumatology criteria for 20% improvement (ACR20), 50% improvement (ACR50), and 70% improvement (ACR70) at week 24. B, The proportion of patients who achieved remission based on the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (<2.6) at week 24. C, The mean change from baseline in the modified Sharp/van der Heijde score (mTSS) every other week.

Figure 3

The proportion of patients treated with either subcutaneous tocilizumab (TCZ-SC; n = 437) or placebo (PBO-SC; n = 219) every other week (q2w) who achieved the American College of Rheumatology (ACR) criteria for 20% improvement (ACR20), 50% improvement (ACR50), and 70% improvement (ACR70) at week 24, stratified by weight (intent-to-treat population).