Effects of concomitant glucocorticoids in TOZURA, a common-framework study programme of subcutaneous tocilizumab in rheumatoid arthritis

Abstract

Objectives: This post hoc analysis of the TOZURA study programme evaluated the efficacy and safety of subcutaneous tocilizumab (TCZ-SC) as monotherapy or with concomitant conventional synthetic DMARDs (csDMARDs) in patients with RA categorized by baseline glucocorticoid (GC) use.

Methods: TOZURA was a multinational, open-label, single-arm, common-framework study programme (11 protocols, 22 countries) in patients with moderate to severe RA in whom csDMARDs or biologic therapies had failed or who were MTX naïve. Patients received once-weekly TCZ-SC 162 mg for ⩾24 weeks as monotherapy or in combination with csDMARDs and/or oral GC use (⩽10 mg/day prednisone or equivalent), which was to be continued unchanged for 24 weeks. Treatment subgroups were defined by baseline GC use and analysed for efficacy and safety.

Results: Of 1804 patients who received TCZ-SC, 145 received monotherapy + GC, 208 received monotherapy without GC, 730 received combination therapy + GC and 721 received combination therapy without GC. The median GC dose in both GC subgroups was 5 mg/day. The proportion of patients who achieved clinical remission, defined as DAS in 28 joints using ESR <2.6, increased similarly from baseline to week 24 in all subgroups. Improvements in patient-reported outcomes were similar in all subgroups. Overall adverse event profiles were generally similar between subgroups, with some slight numerical differences between GC and non-GC subgroups.

Conclusion: The incremental efficacy benefits of TCZ-SC as monotherapy and in combination with csDMARDs were similar between patients with and without previous and continued oral GC treatment, with generally similar safety profiles.

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

Keywords: RA; biologic therapies; csDMARDs; glucocorticoid; tocilizumab.

Fig. 1

Efficacy of TCZ-SC over 24 weeks in subgroups of patients with RA treated with TCZ-SC Percentage of patients in clinical remission (DAS28-ESR <2.6) over 24 weeks in subgroups of patients with RA treated with (A) TCZ-SC monotherapy or (B) TCZ-SC + csDMARD. TJC28 over 24 weeks in subgroups of patients with RA treated with TCZ-SC in subgroups of patients with RA treated with (C) TCZ-SC monotherapy or (D) TCZ-SC + csDMARD. SJC28 over 24 weeks in subgroups of patients with RA treated with (E) TCZ-SC monotherapy or (F) TCZ-SC + csDMARD. csDMARD: conventional synthetic DMARD; DAS28-ESR: DAS in 28 joints using ESR; GC: glucocorticoid; SJC28: swollen joint count in 28 joints; TCZ-SC: subcutaneous tocilizumab; TJC28: tender joint count in 28 joints.

Fig. 2

FACIT-F score over 24 weeks in subgroups of patients with RA treated with (A) TCZ-SC monotherapy or (B) TCZ-SC + csDMARD csDMARD: conventional synthetic DMARD; FACIT-F: Functional Assessment of Chronic Illness Therapy-Fatigue; GC: glucocorticoid; TCZ-SC: subcutaneous tocilizumab.

Fig. 3

HAQ-DI score over 24 weeks in subgroups of patients with RA treated with (A) TCZ-SC monotherapy or (B) TCZ-SC + csDMARD csDMARD: conventional synthetic DMARD; GC: glucocorticoid; HAQ-DI: HAQ-Disability Index; TCZ-SC: subcutaneous tocilizumab.