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Serum cytokines and bone metabolic markers in patients with rheumatoid arthritis treated with biological disease modifying anti-rheumatic drugs

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Abstract

Introduction

/objectives

Several biological disease-modifying anti-rheumatic drugs (bDMARDs) have been widely used for the management of rheumatoid arthritis (RA). These drugs target different molecules important for the pathophysiology of RA; however, only a few studies have compared the effects of these biological drugs on cytokines and bone metabolic markers. The main aim of this study is to clarify the effects of bDMARDs with different modes of action on the cytokine and bone metabolic marker levels in patients with RA.

Methods

Patients with RA who were initiated on infliximab, tocilizumab, or abatacept as the first bDMARD were prospectively enrolled in this study. Serum cytokine and bone metabolic marker levels were measured longitudinally, and changes in their levels were compared.

Results

A total of 174 patients were enrolled in this study, with 55, 70, and 49 patients in the infliximab, tocilizumab, and abatacept groups, respectively. At six months, despite the similar clinical effectiveness of the three drugs, changes in the cytokine and bone metabolic marker levels were distinct; interferon-γ and tumor necrosis factor-α levels were significantly increased with infliximab, interleukin-6 levels were increased with tocilizumab, and interleukin-1β and interleukin-8 levels were increased with abatacept treatment. Bone-specific alkaline phosphatase and osteocalcin levels increased more significantly with tocilizumab than with infliximab, while osteopontin and osteonectin levels decreased with infliximab treatment.

Conclusions

bDMARDs with different modes of action exert different effects on the cytokine and bone metabolic marker levels in patients with RA.

Key Points

• While clinical effectiveness is comparable with infliximab, tocilizumab, and abatacept in patients with rheumatoid arthritis, changes in cytokine and bone metabolic marker levels are distinct among bDMARDs.

• Especially, changes in interferon-γ, tumor necrosis factor-α levels with infliximab, interleukin-6, bone-specific alkaline phosphatase, osteocalcin levels with tocilizumab, and interleukin-1β, interleukin-8 levels with abatacept are significant.

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Data availability

The data that underlie this article will be shared if a reasonable request is made to the corresponding author.

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Acknowledgements

The authors would like to thank Ms. H Kondo for her help with patients’ recruitment, and Ms. Y Ikeda for her technical support.

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Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan

    Hiroya Tamai, Jun Kikuchi, Keisuke Izumi, Keiko Yoshimoto, Tsutomu Takeuchi & Yuko Kaneko

  2. Nishina Medical Clinic, Nagano, Japan

    Naoshi Nishina

  3. Division of Rheumatology, Department of Medicine, National Tokyo Medical Center, Tokyo, Japan

    Keisuke Izumi

  4. Otomo Rheumatology Clinic, Tokyo, Japan

    Kotaro Otomo

  5. Department of Rheumatology and Infectious Diseases, Kitasato University School of Medicine, Kanagawa, Japan

    Kunihiro Yamaoka

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  1. Hiroya Tamai
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  2. Naoshi Nishina
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  4. Keisuke Izumi
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Contributions

Hiroya Tamai contributed to the acquisition of and maintaining the data, analysis of the data, interpretation of the results, and writing the manuscript. Naoshi Nishina, Jun Kikuchi, Keisuke Izumi, Keiko Yoshimoto, and Kunihiro Yamaoka contributed to the acquisition of and maintaining the data, interpretation of the results, and critically reviewed the manuscript. Kotaro Otomo contributed to the interpretation of the results and critically reviewed the manuscript. Tsutomu Takeuchi contributed to the design of the study and interpretation of the results and critically reviewed the manuscript. Yuko Kaneko contributed to the design of the study, interpretation of the result, writing the manuscript and critically reviewed the manuscript. All authors finally approved the final version of manuscript.

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Correspondence to Hiroya Tamai.

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Conflict of interest

Dr. Tamai received honoraria from AbbVie and Eisai. Dr. Kikuchi received honoraria from Bristol Myers Squibb, Chugai and Mitsubishi-Tanabe. Dr. Izumi received honoraria from AbbVie, Asahi-Kasei, Ayumi, Bristol Myers Squibb, Chugai, Eisai and Eli Lilly. Dr. Otomo received honoraria from AbbVie, Asahi Kasei, Astellas, Bristol-Myers Squibb, Chugai, Eli Lilly, Glaxo SmithKline, Jansen, Mitsubishi-Tanabe, Novartis, Pfizer, Sanofi and UCB. Dr. Yamaoka received honoraria from Pfizer, Chugai Pharma, Takeda Industrial Pharma, Astellas Pharma, Abbvie, Bristol-Myers Squibb, Mitsubishi-Tanabe Pharma, GlaxoSmithkline, Eli Lilly, Janssen Pharma, Eisai Pharma, Actelion Pharmaceuticals Japan, Asahikasei Pharma Corp, Ono Pharma, Otsuka Pharma, Nippon Shinyaku, Gilead G.K, Daiichi Sankyo, Boehringer Ingelheim Japan, Japan Tobacco Inc., Hisamitsu Pharma Co, MSD, Sanofi, AYUMI Pharma Co, and Nippon Kayaku. Dr. Takeuchi received honoraria from Astellas, AbbVie, Ayumi, Bristol Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Glaxo Smith Kline, Janssen, Mitsubishi-Tanabe, Nippon-kayaku, Novartis, Pfizer, Sanofi, UCB and research support from Asahi Kasei, AbbVie, Ayumi, Boehringer-Ingelheim, Chugai, Eisai, Eli Lilly, Mitsubishi-Tanabe, Sanofi, and UCB. Dr. Kaneko received honoraria from Asahi Kasei, Astellas, Ayumi, Bristol Myers Squibb, Chugai, Eisai, Elli Lilly, Mitsubishi-Tanabe, Novartis, UCB, and research support from AbbVie, Chugai, Eisai, Mitsubishi-Tanabe, and UCB. The other authors declare no relevant conflicts of interest.

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Tamai, H., Nishina, N., Kikuchi, J. et al. Serum cytokines and bone metabolic markers in patients with rheumatoid arthritis treated with biological disease modifying anti-rheumatic drugs. Clin Rheumatol 42, 721–730 (2023). https://doi.org/10.1007/s10067-022-06390-x

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