Head-to-head comparison of the safety of tocilizumab and tumor necrosis factor inhibitors in rheumatoid arthritis patients (RA) in clinical practice: results from the registry of Japanese RA patients on biologics for long-term safety (REAL) registry

Ryoko Sakai,Michi Tanaka,Taichi Hayashi,Hiroaki Dobashi,Hayato Nagasawa,Kaori Watanabe,Kazuyoshi Saito,Shintaro Hirata,Yoshiya Tanaka,Toshihiro Nanki,Koichi Amano,Tetsuji Sawada,Kazuhiko Ezawa,Ryuji Koike,Takahiko Sugihara,Shinsuke Yasuda,Kiyoshi Migita,Masayoshi Harigai,Takayuki Sumida,Nobuyuki Miyasaka,Atsushi Ueda ,Soo Kyung Cho ,Haruka Yamazaki ,Tomoyuki Fujii

doi:10.1186/s13075-015-0583-8

Abstract

IntroductionThe objective of this study was to directly compare the safety of tocilizumab (TCZ) and TNF inhibitors (TNFIs) in rheumatoid arthritis (RA) patients in clinical practice.MethodsThis prospective cohort study included RA patients starting TCZ [TCZ group, n = 302, 224.68 patient-years (PY)] or TNFIs [TNFI group, n = 304, 231.01 PY] from 2008 to 2011 in the registry of Japanese RA patients on biologics for long-term safety registry. We assessed types and incidence rates (IRs) of serious adverse events (SAEs) and serious infections (SIs) during the first year of treatment. Risks of the biologics for SAEs or SIs were calculated using the Cox regression hazard analysis.ResultsPatients in the TCZ group had longer disease duration (P <0.001), higher disease activity (P = 0.019) and more frequently used concomitant corticosteroids (P <0.001) than those in the TNFI group. The crude IR (/100 PY) of SIs [TCZ 10.68 vs. TNFI 3.03; IR ratio (95% confidence interval [CI]), 3.53 (1.52 to 8.18)], but not SAEs [21.36 vs. 14.72; 1.45 (0.94 to 2.25)], was significantly higher in the TCZ group compared with the TNFI group. However, after adjusting for covariates using the Cox regression hazard analysis, treatment with TCZ was not associated with higher risk for SAEs [hazard ratio (HR) 1.28, 95% CI 0.75 to 2.19] or SIs (HR 2.23, 95% CI 0.93 to 5.37).ConclusionsThe adjusted risks for SAEs and SIs were not significantly different between TCZ and TNFIs, indicating an influence of clinical characteristics of the patients on the safety profile of the biologics in clinical practice.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0583-8) contains supplementary material, which is available to authorized users.

Highlights

The objective of this study was to directly compare the safety of tocilizumab (TCZ) and TNF inhibitors (TNFIs) in rheumatoid arthritis (RA) patients in clinical practice
After adjusting for age, gender, disease activity score including 28-joint count C-reactive protein (3), comorbidity, use of oral corticosteroids ≥5 mg/day, and Steinbrocker’s class, the hazard ratio (HR) of the use of TCZ compared to the use of TNFI for developing serious adverse event (SAE) was 1.28, not significantly elevated (Table 3)
We evaluated the risk of use of TCZ for development of SAEs in patients given MTX at baseline as a sensitivity analysis, and found the HR of use of TCZ was 1.21 (0.55 to 2.65, P = 0.632) compared to the use of TNFI (Table 3)

Summary

Introduction

The objective of this study was to directly compare the safety of tocilizumab (TCZ) and TNF inhibitors (TNFIs) in rheumatoid arthritis (RA) patients in clinical practice. Tocilizumab (TCZ), which is a humanized antibody against the interleukin 6 (IL-6) receptor [1], inhibits signaling mediated by IL-6 [2] and was first approved to treat rheumatoid arthritis (RA) in Japan in 2008. TCZ showed excellent effectiveness in patients with established RA [13]. Safety profiles of TCZ in patients with RA were clarified by the Japanese post-marketing surveillance (PMS) program [14] and a meta-analysis [15]. The favorable benefit-risk balance of TCZ has led to the worldwide use of this biologic for treating RA [16]

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