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

ObjectivesThis 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).MethodsPatients (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.ResultsAt 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.ConclusionsTocilizumab-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.

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.…”

“…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. Since TCZ‐SC is a fixed‐dose regimen, in order to maintain the efficacy, weekly administration of TCZ‐SC may be beneficial for restoring a sufficient serum concentration of TCZ in patients with high body weights who have inadequate responses to biweekly TCZ‐SC.…”

“…Since TCZ‐SC is a fixed‐dose regimen, in order to maintain the efficacy, weekly administration of TCZ‐SC may be beneficial for restoring a sufficient serum concentration of TCZ in patients with high body weights who have inadequate responses to biweekly TCZ‐SC. Weekly administration of TCZ would be expected to be tolerable, because the safety profile of administration of TCZ‐SC 162 mg/2 weeks was similar to that of TCZ‐IV 8 mg/kg/4 weeks, except for injection site reactions, in the SUMMACTA study 10 and the open‐label extension of the MUSASHI study 15. Further studies are needed to investigate the potential benefits and adverse events of TCZ administered weekly.…”

“…In the present study, one patient newly developed anti‐TCZ antibody after switching in the TCZ IV/SC group, although this patient experienced neither a reduction of efficacy nor a systemic injection reaction. An earlier report demonstrated the incidence of anti‐TCZ antibody to be low, with no difference between TCZ‐SC and TCZ‐IV, and no correlation was observed between antibody development and either adverse events or clinical responsiveness 10. Therefore, the immunogenicity potential following switching from TCZ‐IV to TCZ‐SC monotherapy was considered to be low based on the available data.…”

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

“…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 .…”