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Clinical trial: effects of an oral preparation of mesalazine at 4 g/day on moderately active ulcerative colitis. A phase III parallel-dosing study

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Abstract

Background and aims

Oral mesalazine formulations are effective in the treatment of active ulcerative colitis (UC). It is not clear what induction dose of mesalazine is optimal for treating patients with active UC. We aimed to evaluate the efficacy and safety of 4 versus 2.25 g/day for selected patients with active UC.

Methods

A multicenter, randomized, double-blind, parallel-group clinical study in 39 Japanese medical institutions. A total of 123 patients with moderately active UC received 4 g/day (two divided doses) versus 2.25 g/day (three divided doses) for 8 weeks. Primary endpoint was the ulcerative colitis-disease activity index (UC-DAI) score before and after 8 weeks of treatment. The improvement of each individual UC-DAI variable, remission, and efficacy rates were secondary endpoints. Safety was determined by laboratory data, vital signs, subjective symptoms, and objective findings.

Results

Patients receiving 4 g/day achieved a change in UC-DAI score significantly superior to those receiving 2.25 g/day [−3.0 (95% confidence intervals (CI) −3.8 to −2.3) vs. −0.8 (95% CI −1.8 to 0.1), respectively]. There were significant differences in all UC-DAI variables between the groups. Remission rates were 22.0% (4 g/day) and 15.3% (2.25 g/day). The efficacy rate was significantly better with 4 versus 2.25 g/day [76.3 vs. 45.8%, respectively (95% CI 13.8–47.2); P = 0.001]. No difference was seen in adverse events or adverse drug reactions.

Conclusions

A dose of 4 g/day was significantly superior to 2.25 g/day in terms of UC-DAI score for patients with moderately active UC. Safety profiles were similar for both doses.

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Acknowledgments

The authors would like to thank all patients and investigators for their participation in this study (Appendix).

Author information

Authors and Affiliations

  1. Department of Gastroenterology, Iwaki Kyoritsu General Hospital, 16 Kusehara, Mimayamachi, Uchigo, Iwaki, 973-8555, Japan

    Nobuo Hiwatashi

  2. Department of Internal Medicine, Toho University Sakura Medical Center, 564-1 Shimoshizu, Sakura, Chiba, 285-8741, Japan

    Yasuo Suzuki

  3. Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan

    Keiichi Mitsuyama

  4. First Division of Internal Medicine, Hirosaki University School of Medicine, 5 Zaifucho, Hirosaki, Aomori, 036-8562, Japan

    Akihiro Munakata

  5. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinano-machi, Shinjuku, Tokyo, 160-8582, Japan

    Toshifumi Hibi

Authors
  1. Nobuo Hiwatashi
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  2. Yasuo Suzuki
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  3. Keiichi Mitsuyama
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  4. Akihiro Munakata
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  5. Toshifumi Hibi
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Corresponding author

Correspondence to Nobuo Hiwatashi.

Appendix

Appendix

Toho University Sakura Medical Center: Yasuo Suzuki; Sai Clinic: Soken Sai; Sapporo-Kosei General Hospital: Sei Kurokawa; Social Insurance Chuo General Hospital: Masakazu Takazoe; Hidaka Clinic: Hisamitsu Hidaka; Yokoyama Gastrointestinal Division Hospital: Tadashi Yokoyama; Osaka Police Hospital: Takashi Abe; Matsushima Hospital: Haruo Nishino; Yokkaichi Social Insurance Hospital: Satoru Umegae; Osaka City University Hospital: Nobuhide Oshitani; Fukuoka University Chikushi Hospital: Sumio Tsuda; Kurume University Hospital: Keiichi Mitsuyama; Asahikawa-Kosei General Hospital: Masanori Murakami; Showa University Hospital: Yoshiaki Takeuchi; Chiba University Hospital: Tatsuro Katsuno; Jikeikai University Aoto Hospital: Yoshio Aizawa; Toho University Omori Medical Center: Hidenori Kurakata; Fujita Gastrointestinal Division Hospital: Hitoshi Hongo; Hyogo College of Medicine Hospital: Takayuki Matsumoto; Kurume Coloproctology Center: Yasumi Araki; Asahikawa Medical College Hospital: Toshifumi Ashida; Tohoku University Hospital: Yoshitaka Kinouchi; Yokohama City University Medical Center: Reiko Kunisaki; Yokoyama Shin-midori General Hospital: Takashi Kirita; Keio University Hospital: Haruhiko Ogata; Aichi Medical University Hospital: Mitsuki Miyata; Higashisumiyoshi Morimoto Hospital: Masaki Iimuro; Japanese Red Cross Kyoto Daiichi Hospital: Yusuke Okuyama; Kobe Ekisaikai Hospital: Makoto Yamamura; Osaka General Hospital of West Japan Railway Company: Seiji Shimizu; Usui Internal Medicine/Gastroenterology Department Clinic: Tatsuhiko Usui; Fukuoka University Hospital: Kunihiko Aoyagi; Asahikawa City Hospital: Masaki Taruishi; Juntendo University Hospital: Toshifumi Okusa; Jikei University Third Hospital: Hisato Nakajima; Arakawa Hospital: Yoshio Matsuda; Fukui Naika Ichouka Clinic: Shin Fukui; Kobe City Medical Center General Hospital: Chiharu Kawanami; Yame General Hospital: Hideo Tateishi.

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Hiwatashi, N., Suzuki, Y., Mitsuyama, K. et al. Clinical trial: effects of an oral preparation of mesalazine at 4 g/day on moderately active ulcerative colitis. A phase III parallel-dosing study. J Gastroenterol 46, 46–56 (2011). https://doi.org/10.1007/s00535-010-0308-3

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  • DOI: https://doi.org/10.1007/s00535-010-0308-3

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