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C-reactive protein is an indicator of serum infliximab level in predicting loss of response in patients with Crohn’s disease

  • Original Article—Alimentary Tract
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Abstract

Background

The ability of serum infliximab level to predict clinical outcome in infliximab therapy in Crohn’s disease is unclear. Here, we aimed to clarify the correlation between the timing of loss of response (LOR) to treatment and a decrease in serum infliximab level, and, in addition, to identify an indicator of infliximab level.

Methods

The study used data from a previous clinical study of infliximab for Crohn’s disease, in which infliximab was initially given at 0, 2, 6 weeks at 5 mg/kg, and then at 8-week intervals to 62 week-10 responders. Of these 62, here we analysed data from 57 in whom Crohn’s disease activity index and serum infliximab level were evaluated at week 14.

Results

Twelve patients showed a clinical response despite an infliximab level <1 μg/mL at week 14; of these, 8 (67 %) experienced LOR by week 54. A decrease in infliximab level preceded LOR in 6 (75 %). In receiver operating characteristic curve analysis, C-reactive protein (CRP) showed better performance in detecting an infliximab level <1 μg/mL. Infliximab level was <1 μg/mL in 60–80 % of patients with CRP >0.5 mg/dL. Time to LOR (median: 22.0 weeks) was significantly longer than that to a decrease in infliximab level to <1 μg/mL (14.0 weeks, p < 0.05) or to an increase in CRP to >0.5 mg/dL (14.0 weeks, p < 0.01).

Conclusions

A decrease in serum infliximab level preceded LOR, and was easily detected by an increase in CRP. The CRP may be an indicator of serum infliximab level in predicting LOR.

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Acknowledgments

This study was sponsored by Mitsubishi Tanabe Pharma Corporation. The authors thank the patients, investigators, and study personnel who made the trial possible. We also thank the following investigators for their involvement: Noriaki Watanabe (Department of Internal Medicine, Kitasato Institute Hospital, Tokyo, Japan), Tomoe Katsumata (Department of Gastroenterology, Kitasato University East Hospital, Sagamihara, Japan), Hidemi Goto (Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya, Japan), Akiyoshi Nishio (Department of Gastroenterological Endoscopy, Kyoto University Hospital, Kyoto, Japan).

Conflict of interest

T. Hibi has received grant/research support from Ajinomoto Pharmaceuticals, JIMRO, and Mitsubishi Tanabe Pharma. M. Watanabe has received grant/research support and lecture fees from Abbott Japan, Ajinomoto Pharmaceuticals, Asahi Kasei Medical, Astellas Pharma, AstraZeneca, Chugai Pharmaceutical, DAIICHI SANKYO, Eisai, JIMRO, Kyorin Pharmaceutical, Kyowa Hakko Kirin, Mitsubishi Tanabe Pharma, MSD, Otsuka Pharmaceutical, UCB Japan, and Zeria Pharmaceutical. H. Ito has received lecture fees from Mitsubishi Tanabe Pharma. N. Sato and T. Yoshinari are employees of Mitsubishi Tanabe Pharma. Y. Suzuki has received lecture fees from Mitsubishi Tanabe Pharma. T. Matsumoto has received grant/research support from Asahi Kasei Medical, Ajinomoto Pharmaceuticals, Astellas Pharma, Eisai, EN Otsuka Pharmaceutical, Kyorin Pharmaceutical, Mitsubishi Tanabe Pharma, Otsuka Pharmaceutical, Otsuka Pharmaceutical Factory, UCB Japan, and Zeria Pharmaceutical. The other authors have no conflict of interest.

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Toshifumi Hibi & Atsushi Sakuraba

  2. Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan

    Mamoru Watanabe

  3. Inflammatory Bowel Diseases Center, Sapporo-Kosei General Hospital, Sapporo, Japan

    Satoshi Motoya

  4. Kinshukai Infusion Clinic, Osaka, Japan

    Hiroaki Ito

  5. Mitsubishi Tanabe Pharma Corporation, Osaka, Japan

    Noriko Sato & Toru Yoshinari

  6. Department of Gastroenterology, Gunma Prefectural Cancer Center, Ota, Japan

    Kenta Motegi

  7. Health Administration Center, Center for the Advancement of Higher Education, Tohoku University Graduate School of Medicine, Sendai, Japan

    Yoshitaka Kinouchi

  8. Inflammatory Bowel Diseases Center, Social Insurance Central General Hospital, Tokyo, Japan

    Masakazu Takazoe

  9. Department of Internal Medicine, Toho University Sakura Medical Center, Sakura, Japan

    Yasuo Suzuki

  10. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Takayuki Matsumoto

  11. Matsuda Hospital Colo-Proctological Institute, Hamamatsu, Japan

    Kazuhiko Kawakami

  12. Department of Lower Gastroenterology, Hyogo College of Medicine, Nishinomiya, Japan

    Takayuki Matsumoto

  13. Department of Gastroenterology, Fujita Health University, Toyoake, Japan

    Ichiro Hirata

  14. Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan

    Shinji Tanaka

  15. The Third Department of Internal Medicine, Asahikawa Medical College, Asahikawa, Japan

    Toshifumi Ashida

  16. Department of Gastroenterology, Fukuoka University Chikushi Hospital, Chikushino, Japan

    Toshiyuki Matsui

Authors
  1. Toshifumi Hibi
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  2. Atsushi Sakuraba
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  3. Mamoru Watanabe
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  4. Satoshi Motoya
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  11. Yasuo Suzuki
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  16. Shinji Tanaka
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  17. Toshifumi Ashida
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  18. Toshiyuki Matsui
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Corresponding author

Correspondence to Toshifumi Hibi.

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Hibi, T., Sakuraba, A., Watanabe, M. et al. C-reactive protein is an indicator of serum infliximab level in predicting loss of response in patients with Crohn’s disease. J Gastroenterol 49, 254–262 (2014). https://doi.org/10.1007/s00535-013-0807-0

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  • DOI: https://doi.org/10.1007/s00535-013-0807-0

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