Predictive value of serum amyloid a levels for requirement of concomitant methotrexate in tocilizumab initiation: A post hoc analysis of the SURPRISE study

Abstract

Objectives: To identify predictive factors for remission by tocilizumab monotherapy in rheumatoid arthritis (RA) patients.

Methods: This is a post hoc analysis of the SURPRISE study, a 2-year randomized, controlled study comparing the efficacy of tocilizumab with (ADD-ON) and without methotrexate (SWITCH). The primary endpoint was DAS28-ESR remission (<2.6) at week 24. The change in modified total Sharp score from baseline to week 52 (ΔmTSS/year) was also assessed as an endpoint. The effect of clinical parameters at baseline on remission was estimated by logistic regression analysis.

Results: In SWITCH (n = 96), CRP, SAA, RF, and DAS28 at baseline showed predictive value for DAS28 remission in unadjusted analysis. Adjusted analysis confirmed SAA and DAS28 as predictive factors, with SAA having the highest value (ROC-AUC = 0.731). Furthermore, structural remission (ΔmTSS/year ≤ 0.5) rate was significantly higher in patients with SAA of < 50.0 μg/mL than other patients. In contrast, in ADD-ON (n = 98), only DAS28 showed predictive value for DAS28 remission. In patients with SAA < 50.0 μg/mL, both DAS28 remission and structural remission rate were comparable between SWITCH and ADD-ON.

Conclusion: RA patients with low SAA levels at baseline may benefit similarly from tocilizumab with and without methotrexate.

Trial registration number: NCT01120366.

Keywords:

• Monotherapy
• prediction
• remission
• serum amyloid A
• tocilizumab

Acknowledgments

The authors acknowledge and thank all the investigators and participants in this study.

Collaborators

Other investigators of the SURPRISE study group: Takao Fujii (Kyoto University), Atsushi Kawakami (Nagasaki University Graduate School of Biomedical Sciences), Hideshi Yamazaki (Marunouchi Hospital), Yasuaki Okuda (Dohgo Spa Hospital), Kazuhide Tanimura (Hokkaido Medical Center for Rheumatic Diseases), Atsushi Kaneko (Nagoya Medical Center), Toshio Tanaka (Osaka University), Akira Murasawa (Niigata Rheumatic Center), Kazuhiko Ezawa (Kurashiki Sweet Hospital), Yukitaka Ueki (Sasebo Chuo Hospital), Yoshiki Shiohira (Yuuaikai Tomishiro Central Hospital), Hiroaki Dobashi (Kagawa University), Naoki Kondo (Niigata University Graduate School of Medical and Dental Sciences), Toshihiko Hidaka (Zenjinkai Shimin-no-Mori Hospital), Hajime Sano (Hyogo College of Medicine), Mitsuhiro Iwahashi (Higashi Hiroshima Memorial Hospital), Motohiro Oribe (Oribe Clinic of Rheumatism and Medicine), Shohei Nagaoka (Yokohama Minami Kyosai Hospital), and Kensei Tsuzaka (Tokyo Dental College Ichikawa General Hospital).

Conflict of interest

M. K. has received research grants or lecture fees from GlaxoSmithKline and Actelion. Y. K. has received grants from Abbvie and Eisai and speaking fees from AbbVie, Astellas, Ayumi, Bristol-Myers Squibb, Chugai, Eisai, Eli Lilly, Jansen, Kissei, Pfizer, Sanofi, Takeda, Mitsubishi Tanabe and UCB. Y. T. has received grants from Mitsubishi Tanabe, Bristol-Myers Squibb, Eisai, Chugai, Takeda, Abbvie, Astellas, Daiichi-Sankyo, Ono, MSD, and Taisho Toyama and speaking fees from Daiichi-Sankyo, Astellas, Eli Lilly, Chugai, Sanofi, Abbvie, YL Bio, Bristol-Myers Squibb, GlaxoSmithkline, UCB, Mitsubishi Tanabe, Novartis, Eisai, Takeda, Janssen, and Asahi-Kasei. K. A. has received research grants from Asahi Kasei Pharma and speaking fees from AbbVie, Chugai, Eli Lilly, Mitsubishi Tanabe and Pfizer. M. M. has received lecture fee from Chugai, Abbie, Bristol-Myers Squibb, Eisai, Takeda, Janssen, Eli Lilly, Pfizer, and UCB. Y. M. has received grants from AsahiKasei Pharma, Chugai, Ono, Daiichi Sankyo, Teijin, Eisai, NipponKayaku and Mitsubishi Tanabe, instructor fees from Kissei, Janssen and Eisai and speaking fees from Ono, Mitsubishi Tanabe, Astellas, UCB, Chugai, AbbVie, Daiichi-Sankyo, Ayumi, Janssen, Takeda, Sanofi, Teijin, Eli Lilly and Eisai. S. H. has received grants from Eli Lilly and UCB, consultant fees from Bristol-Myers Squibb, Jansen and UCB, lecture fees from AbbVie, Eisai and Mitsubishi Tanabe and speaking fees from AbbVie, Astellas, Ayumi, Bristol-Myers Squibb, Chugai, Eisai, Eli Lilly, Jansen, Kissei, Pfizer, Sanofi, Takeda, Mitsubishi Tanabe, and UCB. E. T. has received speaking fees from Abbvie, Asahi Kasei Pharma, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisail, Janssen, Nippon Kayaku, Pfizer, Takeda, Taisho Toyama and UCB. H. Y. has received research grants from AbbVie, Eisai, Bristol-Meyers Squibb, Novartis, Behringer, Astellas, Kaken, Nippon-Shinyaku, Pfizer, UCB, Ayumi, Ono, Daiichi-Sankyo, TaishoToyama, Takeda, Mitsubishi Tanabe, Chugai, Teijin, Torii and YL Bio, consultant fees from Teijin and YLBio and speaking fees from AbbVie, Eisai, Bristol-Myers Squibb, Astellas, Pfizer, UCB, Ayumi, Daiichi-Sankyo, Takeda, Mitsubishi Tanabe, Chugai, Teijin and YLBio. K. Y. has received grants from Chugai, and Takada and speaking fees from Chugai, Mitsubishi Tanabe, Eisai, AbbVie, Astellas, Bristol-Myers Squibb, UCB, Janssen Pharmaceutical, Ono and AYUMI. IY has received speaking fees from Chugai. T. A. has received research grants from Astellas, Takeda, Mitsubishi Tanabe, Chugai, Daiichi-Sankyo, Otsuka, Pfize, Alexion, Bayer, Otsuka, Chugai, Takeda, Eisai, Bristol-Myers Squibb, Daiichi Sankyo, Mitsubishi Tanabe and AsahiKasei, consultant fees from Ono, Sanofi, Daiichi Sankyo and Pfizer and speaking fees from Mitsubishi Tanabe, Chugai, Astellas, Takeda, Pfizer, Daiichi Sankyo, Bristol-Myers Squibb and Eli Lilly. T. T. has received research grants from Astellas, Chugai, Daiichi Sankyo, Takeda, AbbVie, Asahikasei, Mitsubishi Tanabe, Pfizer, Eisai, AYUMI, Nipponkayaku and Novartis, consultant fees from Astra Zeneca, Eli Lilly, Novartis, Mitsubishi Tanabe, Abbivie, Nipponkayaku, Janssen, Astellas. Taiho, Chugai, TaishoToyama, GlaxoSmithKline and UCB and speaking fees from AbbVie, Bristol-Myers Squibb, Chugai, Mitsubishi Tanabe, Pfizer, Astellas, Daiichi Sankyo, Eisai, Sanofi, Teijin Pharma, Takeda and Novartis Pharma. M. I., H. K. –H., N. M., Y. H., and H. N. have nothing to declare.

Additional information

Funding

This study was supported by Specified Nonprofit Corporation Advanced Clinical Research Organization.