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Safety of long-term tacrolimus therapy for rheumatoid arthritis: an open-label, uncontrolled study in non-elderly patients

  • Original Article
  • Published:
Modern Rheumatology

Abstract

In this study we focused on the safety of long-term tacrolimus therapy in non-elderly patients with rheumatoid arthritis who were treated with tacrolimus or mizoribine in a previous double-blind study. The patients received oral tacrolimus at a dose ≤3 mg once daily for 76 weeks. The safety analysis population included 115 patients aged 20–64 years. Adverse drug reactions presented as symptomatic events in 39 patients (33.9%), laboratory abnormalities in 38 patients (33.0%), and infections in 19 patients (16.5%). The major reactions were gastrointestinal disorders and hypertension as symptomatic events, increases of creatinine, urinary N-acetyl-β-d-glucosamidase and hemoglobin A1C as laboratory abnormalities, and the common cold syndrome as infections. After 76 weeks of tacrolimus treatment, the ACR20 response rates of patients who had also received tacrolimus during the preceding double-blind study was 61.5% (compared with the status at baseline in the preceding study). The corresponding response rate for patients who had previously received mizoribine was 66.0%. The mean blood concentration of tacrolimus was 3.8–4.8 ng/mL. In conclusion, safety profiles of tacrolimus treatment for long-term seems to be similar to those of previous studies in patients with rheumatoid arthritis.

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Acknowledgments

We wish to thank the following investigators and institutions for participating in this study: Koji Taneichi, MD (Kitami Red Cross Hospital, Hokkaido); Takashi Murayama, MD and Satoshi Nakazaki, MD (Kanazawa Rehabilitation Hospital, Ishikawa); Seigaku Hayashi, MD (Fukui General Hospital); Takashi Kanno, MD, PhD (Ohta Nishinouchi Hospital, Fukushima); Yuichi Nishioka, MD, PhD (Yamanashi Prefectural Central Hospital, Yamanashi); Makoto Nishinarita, MD, PhD and Shuji Ohta, MD (Taga General Hospital, Ibaraki); Takayuki Sumida, MD, PhD (Tsukuba University Hospital, Ibaraki); Hitoaki Okazaki, MD, PhD (Jichi Medical School Hospital, Tochigi); Shoji Kumaki, MD, PhD (Hokushin General Hospital, Nagano); Kimihiro Suzuki, MD, PhD (National Defense Medical College Hospital, Saitama); Tsutomu Takeuchi, MD, PhD (Saitama Medical Center,Saitama Medical University, Saitama); Fumihiko Imai, MD, PhD (Imai Medical Clinic, Saitama); Naoya Takashina, MD (Takashina Clinic, Tokyo); Shigeru Hosaka, MD (Hosaka Clinic, Tokyo); Shigeto Tohma, MD (Sagamihara National Hospital, National Hospital Organization, Kanagawa); Hirobumi, Kondo, MD, PhD (Kitasato University School of Medicine, Kanagawa); Tadao Mitsui, MD, PhD (Aichi Medical University Hospital, Aichi); Katsuji Shimizu, MD, DMSc (Gifu University School of Medicine and Gifu University Hospital, Gifu); Norikazu Murata, MD, PhD and Osamu Saiki, MD, PhD (National Hospital Organization, Osaka Minami Medical Center, Osaka); Tsukasa Matsubara, MD, PhD (Matsubara Clinic, Hyogo); Keisuke Hashimoto, MD, PhD and Yoshinobu Koyama, MD, PhD (Matsubara Mayflower Hospital, Hyogo); Eisuke Shono, MD, PhD (Fukuoka University Hospital, Fukuoka); Masakazu Kondo, MD (Kondo Clinic of Rheumatology and Orthopaedics, Fukuoka); Hideyuki Ikematsu, MD (Hara-doi Hospital, Fukuoka); and Ryuji Nagamine, MD, PhD (Kyushu Rosai Hospital, Fukuoka). This study was funded by a grant from Astellas Pharma Inc. (Tokyo, Japan). All authors participated as a medical consultant or members of the safety committee of Astellas Pharma Inc. They have received consultant fees from this company.

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Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Toho University School of Medicine, 6-11-1 Omori-Nishi, Ota-ku, Tokyo, 143-8541, Japan

    Shinichi Kawai

  2. Department of Neurology, Toyama University Hospital, Toyama, Japan

    Kortaro Tanaka

  3. Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan

    Iwao Ohno

  4. Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan

    Kazunori Utsunomiya

  5. Internal Medicine, Nippon Medical School Chiba Hokusoh Hospital, Chiba, Japan

    Yoshihiko Seino

Authors
  1. Shinichi Kawai
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  2. Kortaro Tanaka
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  3. Iwao Ohno
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  4. Kazunori Utsunomiya
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  5. Yoshihiko Seino
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Correspondence to Shinichi Kawai.

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Kawai, S., Tanaka, K., Ohno, I. et al. Safety of long-term tacrolimus therapy for rheumatoid arthritis: an open-label, uncontrolled study in non-elderly patients. Mod Rheumatol 18, 345–353 (2008). https://doi.org/10.1007/s10165-008-0058-8

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  • DOI: https://doi.org/10.1007/s10165-008-0058-8

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