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, Soo-Kyung Cho, Toshihiro Nanki, Kaori Watanabe, Hayato Yamazaki, Michi Tanaka, Ryuji Koike, Yoshiya Tanaka, Kazuyoshi Saito, Shintaro Hirata, Koichi Amano, Hayato Nagasawa, Takayuki Sumida, Taichi Hayashi, Takahiko Sugihara, Hiroaki Dobashi, Shinsuke Yasuda, Tetsuji Sawada, Kazuhiko Ezawa, Atsuhisa Ueda, Takao Fujii, Kiyoshi Migita, Nobuyuki Miyasaka, Masayoshi Harigai, REAL Study Group, Tatsuya Atsumi, Yoshiaki Ishigatsubo, Atsushi Ihata, Tsuneyo Mimori, Yoshinari Takasaki, Naoto Tamura, Akira Hashiramoto, Syunichi Shiozawa, Hideto Kameda, Yuko Kaneko, Tsutomu Takeuchi, Sae Ochi, Yasushi Miura, Yoshinori Nonomura, Atsuo Nakajima, Kazuya Michishita, Kazuhiko Yamamoto, Yukitaka Ueki, Kenji Nagasaka, Akitomo Okada, Atsushi Kawakami, Shigeto Tohma, Ayako Nakajima, Hisashi Yamanaka, Ryoko Sakai, Soo-Kyung Cho, Toshihiro Nanki, Kaori Watanabe, Hayato Yamazaki, Michi Tanaka, Ryuji Koike, Yoshiya Tanaka, Kazuyoshi Saito, Shintaro Hirata, Koichi Amano, Hayato Nagasawa, Takayuki Sumida, Taichi Hayashi, Takahiko Sugihara, Hiroaki Dobashi, Shinsuke Yasuda, Tetsuji Sawada, Kazuhiko Ezawa, Atsuhisa Ueda, Takao Fujii, Kiyoshi Migita, Nobuyuki Miyasaka, Masayoshi Harigai, REAL Study Group, Tatsuya Atsumi, Yoshiaki Ishigatsubo, Atsushi Ihata, Tsuneyo Mimori, Yoshinari Takasaki, Naoto Tamura, Akira Hashiramoto, Syunichi Shiozawa, Hideto Kameda, Yuko Kaneko, Tsutomu Takeuchi, Sae Ochi, Yasushi Miura, Yoshinori Nonomura, Atsuo Nakajima, Kazuya Michishita, Kazuhiko Yamamoto, Yukitaka Ueki, Kenji Nagasaka, Akitomo Okada, Atsushi Kawakami, Shigeto Tohma, Ayako Nakajima, Hisashi Yamanaka

Abstract

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.

Methods: This 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.

Results: Patients 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).

Conclusions: The 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.

Figures

Figure 1
Figure 1
Flow chart of rheumatoid arthritis (RA) patients enrolled in this study from the REAL.
Figure 2
Figure 2
Kaplan-Meier curves for time to discontinuation for each group. Drug retention rates were compared using the log-rank test between tocilizumab (TCZ) and tumor necrosis factor inhibitors (TNFIs). The y axis shows the cumulative retention rates.

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Source: PubMed

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