Subcutaneous Tocilizumab Versus Placebo in Combination With Disease‐Modifying Antirheumatic Drugs in Patients With Rheumatoid Arthritis

Abstract

ObjectiveThe 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.MethodsPatients (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.ResultsTCZ-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.ConclusionTCZ-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.

Sustainable Efficacy of Switching From Intravenous to Subcutaneous Tocilizumab Monotherapy in Patients With Rheumatoid Arthritis

“…This study verified the noninferiority of TCZ‐SC 162 mg/2 weeks versus TCZ‐IV 8 mg/kg/4 weeks 9. Furthermore, 2 international phase III studies, SUMMACTA and BREVACTA 10, 11, which compared TCZ‐SC with TCZ‐IV or placebo with DMARDs, were performed. These studies verified not only the noninferiority of TCZ‐SC 162 mg/2 weeks to TCZ‐IV 8 mg/kg/4 weeks, but also compared the superiority of TCZ‐SC 162 mg/2 weeks to placebo.…”

“…Earlier reports are comparable to the present study. In the phase III BREVACTA study, the efficacy of biweekly administration of TCZ‐SC in combination with DMARDs in patients weighing ≥100 kg was lower than the efficacy in lighter‐weight patients 11. Another phase III SUMMACTA study was designed to prevent the serum concentration of TCZ from decreasing in higher‐weight patients, and demonstrated that adequate efficacy of weekly administration of TCZ‐SC with DMARDs could be achieved in patients weighing ≥100 kg 10.…”

Two-year Efficacy and Safety of Subcutaneous Tocilizumab in Combination with Disease-modifying Antirheumatic Drugs Including Escalation to Weekly Dosing in Rheumatoid Arthritis

“…TCZ-SC 162 mg q2w demonstrated significantly greater efficacy, including inhibiting joint damage, versus placebo (PBO)-SC at Week 24. TCZ-SC q2w was well tolerated and its safety profile was consistent with the TCZ-IV profile, except for increased injection-site reactions (ISR) 6 .…”

“…The safety and efficacy of TCZ-SC are comparable with TCZ-IV as monotherapy and with DMARD, and TCZ-SC has been approved for use globally 5,6,7,8,9 .…”

“…The phase III BREVACTA study evaluated the efficacy and safety of biweekly TCZ-SC in combination with DMARD in patients with moderate to severe RA and an inadequate response to DMARD 6 . TCZ-SC 162 mg q2w demonstrated significantly greater efficacy, including inhibiting joint damage, versus placebo (PBO)-SC at Week 24.…”