Safety and tolerability of subcutaneous sarilumab and intravenous tocilizumab in patients with rheumatoid arthritis

Abstract

Objective: Safety and efficacy of mAbs blocking the IL-6 receptor have been established in RA. This is the first analysis examining safety and tolerability of sarilumab and tocilizumab administered as single or multiple doses in patients with RA within the same study.

Methods: In ASCERTAIN, patients were randomized 1: 1: 2 to 24 weeks' double-blind sarilumab 150 or 200 mg every 2 weeks s.c. or tocilizumab 4 mg/kg every 4 weeks i.v., increased to 8 mg/kg if clinically indicated. In Study 1309, patients were randomized 1: 1: 1: 1 to single-dose open-label sarilumab 150 or 200 mg s.c. or tocilizumab 4 or 8 mg/kg i.v.

Results: In ASCERTAIN, incidence of treatment-emergent adverse events was similar between sarilumab and tocilizumab. The most common treatment-emergent adverse events were the following: sarilumab: neutropenia [6 patients (12.2%) in the 150 mg group and 8 (15.7%) in the 200 mg group], nasopharyngitis [6 (12.2%) and 3 (5.9%)], and injection-site erythema [4 (8.2%) and 4 (7.8%)]; tocilizumab: accidental overdose [9 (8.8%)], upper respiratory tract infection [7 (6.9%)] and nausea [7 (6.9%)]. Laboratory changes in both studies included decreased neutrophils and platelets and increased transaminases and lipids. In Study 1309, incidence of absolute neutrophil count <1.0 giga/l was similar between sarilumab and tocilizumab, and occurred more frequently in the higher dose groups. No association between decrease in absolute neutrophil count and increased incidence of infection was observed in either study.

Conclusion: No clinically meaningful differences in treatment-emergent adverse events were observed between sarilumab and tocilizumab. Laboratory changes with sarilumab were within the same range as those with tocilizumab.

Trial registration numbers: ASCERTAIN (NCT01768572); Study 1309 (NCT02097524).

Keywords: RA; intravenous; sarilumab; subcutaneous; tocilizumab.

© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology.

Figures

Fig. 1

Mean change from baseline in ANC ± s.e. by treatment and visit in (A) ASCERTAIN (weeks 1–24), (B) Study 1309 (days 1–29) and (C) Study 1309 (days 1–7) aPatients in the 4/8 mg/kg q4w i.v. group increased their dose to 8 mg/kg at week 4 and remained on 8 mg/kg for the remainder of the study. bThere were four sampling points on day 1: baseline, 1 h, 4 h and 8 h after dosing. ANC: absolute neutrophil count; BL: baseline; q2w: every 2 weeks; q4w: every 4 weeks.

Fig. 2

Mean change from baseline in ALT ± s.e. in ASCERTAIN aPatients in the 4/8 mg/kg q4w i.v. group increased their dose to 8 mg/kg at week 4 and remained on 8 mg/kg for the remainder of the study. ALT: alanine aminotransferase; BL: baseline; q2w: every 2 weeks; q4w: every 4 weeks.