Subcutaneous tocilizumab in rheumatoid arthritis : findings from the common-framework phase 4 study programme TOZURA conducted in 22 countries

Abstract

Objectives. The aim of this pooled analysis of the TOZURA study programme was to evaluate the efficacy and safety of subcutaneous tocilizumab (TCZ-SC) as monotherapy or in combination with conventional synthetic DMARDs (csDMARDs) in patients with moderate to severe RA who had an inadequate response to csDMARD or anti-TNF agent therapy or who were MTX naı¨ve. Methods. TOZURA is a multinational, open-label, single-arm, common-framework, phase 4 study programme (11 protocols, 22 countries). Patients received TCZ-SC 162 mg each week for 524 weeks, administered at the investigator’s discretion, as monotherapy or in combination with a csDMARD. Efficacy, safety and immunogenicity were evaluated; propensity scorebased matching was used for between-group comparisons. Results. Of 1804 patients, 353 (19.6%) received monotherapy and 1451 (80.4%) received combination therapy. The 28-joint DAS using ESR (DAS28-ESR) in both groups decreased significantly from baseline to week 24 (mean change: monotherapy 3.40, combination therapy 3.46), with no significant difference between groups (P = 0.46). The proportion of patients who achieved DAS28-ESR or Clinical Disease Activity Index remission or ACR 20/50/70/90 responses was similar between groups. Overall, 13.9% of patients withdrew—6.2% for safety reasons and 1.6% for insufficient therapeutic response; 5.8% of patients experienced one or more serious adverse events [14.6/100 patient-years (PY)]; six deaths occurred (0.64/100 PY). Conclusion. In a common framework of 11 studies in 22 countries, this phase 4 study programme confirmed TCZ-SC’s known efficacy and safety profile with comparable effects as monotherapy and in combination with csDMARDs.