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 naïve.

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 ⩾24 weeks, administered at the investigator's discretion, as monotherapy or in combination with a csDMARD. Efficacy, safety and immunogenicity were evaluated; propensity score-based 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.

Trial registration: ClinicalTrials.gov (http://www.clinicaltrials.gov) NCT01941940, NCT01941095, NCT01951170, NCT01987479, NCT01988012, NCT01995201, NCT02001987, NCT02011334, NCT02031471, NCT02046603 and NCT02046616.

Fig. 1

Patient disposition at baselinecsDMARD: conventional synthetic disease-modifying anti-rheumatic drug; qw: once weekly; TCZ-SC: subcutaneous tocilizumab.

Fig. 2

DAS28-ESR and CDAI disease activity at week 24 No imputation of data was used. CDAI: Clinical Disease Activity Index; csDMARD: conventional synthetic disease-modifying anti-rheumatic drug; DAS28-ESR: Disease Activity Score in 28 joints using erythrocyte sedimentation rate; TCZ-SC: subcutaneous tocilizumab.

Fig. 3

Mean (A) DAS28-ESR, (B) CDAI score and (C) HAQ-DI score over 24 weeks *P < 0.0001 for TCZ-SC monotherapy comparing week 1 with week 24. **P < 0.0001 for TCZ-SC + csDMARD comparing week 1 with week 24. BL: baseline; CDAI: Clinical Disease Activity Index; csDMARD: conventional synthetic disease-modifying anti-rheumatic drug; DAS28-ESR: Disease Activity Score in 28 joints using erythrocyte sedimentation rate; HAQ-DI: Health Assessment Questionnaire-Disability Index; TCZ-SC: subcutaneous tocilizumab.

Fig. 4

ACR and EULAR responses at week 24 No imputation of data was used. ACR: American College of Rheumatology; csDMARD: conventional synthetic disease-modifying anti-rheumatic drug; EULAR: European League Against Rheumatism; TCZ-SC: subcutaneous tocilizumab.