Skip to main content

Efficacy of apheresis as maintenance therapy for patients with ulcerative colitis in an open-label prospective multicenter randomised controlled trial



Apheresis therapy involves the selective removal of leukocytes and is used to induce remission in ulcerative colitis (UC) patients. The aim of this study was to demonstrate the efficacy and safety of apheresis therapy for maintaining UC remission.


We conducted a multicenter, prospective, randomised-control trial of patients with remitting UC induced by granulocyte and monocyte adsorption apheresis or leukocytapheresis. Patients were randomly assigned to the apheresis group (twice per month for 12 months) or the control group (no apheresis treatment) using a 1:1 allocation ratio. The primary endpoint was the rate of cumulative clinical remission (Mayo score ≤ 2) at 12 months. The secondary endpoints were the rates of clinical remission, endoscopic remission, and complete endoscopic remission at 12 months.


Between March 2013 and March 2017, 164 patients were enrolled. The cumulative remission rate at 12 months was 46.6% in the apheresis group and 36.4% in the control group (p = 0.1621). The rate of endoscopic remission at 12 months was significantly higher in the apheresis group than in the control group (42.5% vs. 25.9%) p = 0.0480). The rate of clinical remission (47.5% vs.32.1%, p = 0.0540) and complete endoscopic remission (33.8% vs.19.8%, p = 0.0513) tended to be higher in the apheresis than in the control group; however, the difference was not significant. No severe adverse events were observed in either group.


Apheresis was well tolerated as maintenance therapy for UC although the cumulative clinical remission rate at 12 months was comparable between the apheresis and control groups.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2


  1. Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353:2462–76.

    CAS  Article  Google Scholar 

  2. Adalimumab in the Treatment of Moderate-to-Severe Ulcerative Colitis. ULTRA 2 trial results. Gastroenterol Hepatol (NY). 2013;9:317–20.

    Google Scholar 

  3. Sandborn WJ, Feagan BG, Marano C, et al. Subcutaneous golimumab induces clinical response and remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014;146:85–95.

    CAS  Article  Google Scholar 

  4. Sandborn WJ, Feagan BG, Marano C, et al. Subcutaneous golimumab maintains clinical response in patients with moderate-to-severe ulcerative colitis. Gastroenterology. 2014;146:96–109.

    CAS  Article  Google Scholar 

  5. Ogata H, Matsui T, Nakamura M, et al. A randomised dose finding study of oral tacrolimus (FK506) therapy in refractory ulcerative colitis. Gut. 2006;55:1255–62.

    CAS  Article  Google Scholar 

  6. Feagan BG, Rutgeerts P, Sands BE, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013;369:699–710.

    CAS  Article  Google Scholar 

  7. Sandborn WJ, Su C, Sands BE, et al. Tofacitinib as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2017;376:1723–36.

    CAS  Article  Google Scholar 

  8. Shimoyama T, Sawada K, Hiwatashi N, et al. Safety and efficacy of granulocyte and monocyte adsorption apheresis in patients with active ulcerative colitis: a multicenter study. J Clin Apher. 2001;16:1–9.

    CAS  Article  Google Scholar 

  9. Sawada K, Ohnishi K, Kosaka T, et al. Leukocytapheresis with leukocyte removal filter as new therapy for ulcerative colitis. Ther Apher. 1997;1:207–11.

    CAS  Article  Google Scholar 

  10. Hanai H, Watanabe F, Yamada M, et al. Adsorptive granulocyte and monocyte apheresis versus prednisolone in patients with corticosteroid-dependent moderately severe ulcerative colitis. Digestion. 2004;70:36–44.

    CAS  Article  Google Scholar 

  11. Naganuma M, Funakoshi S, Sakuraba A, et al. Granulocytapheresis is useful as an alternative therapy in patients with steroid-refractory or -dependent ulcerative colitis. Inflamm Bowel Dis. 2004;10:251–7.

    Article  Google Scholar 

  12. Sands BE, Sandborn WJ, Feagan B, et al. A randomized, double-blind, sham-controlled study of granulocyte/monocyte apheresis for active ulcerative colitis. Gastroenterology. 2008;135:400–9.

    CAS  Article  Google Scholar 

  13. Sawada K, Muto T, Shimoyama T, et al. Multicenter randomized controlled trial for the treatment of ulcerative colitis with a leukocytapheresis column. Curr Pharm Des. 2003;9:307–21.

    CAS  Article  Google Scholar 

  14. Hanai H, Watanabe F, Takeuchi K, et al. Leukocyte adsorptive apheresis for the treatment of active ulcerative colitis: a prospective, uncontrolled, pilot study. Clin Gastroenterol Hepatol. 2003;1:28–35.

    Article  Google Scholar 

  15. Sawada K, Kusugami K, Suzuki Y, et al. Leukocytapheresis in ulcerative colitis: results of a multicenter double-blind prospective case–control study with sham apheresis as placebo treatment. Am J Gastroenterol. 2005;100:1362–9.

    Article  Google Scholar 

  16. Hibi T, Sameshima Y, Sekiguchi Y, et al. Treating ulcerative colitis by Adacolumn therapeutic leukocytapheresis: clinical efficacy and safety based on surveillance of 656 patients in 53 centres in Japan. Dig Liver Dis. 2009;41:570–7.

    CAS  Article  Google Scholar 

  17. Yokoyama Y, Matsuoka K, Kobayashi T, et al. A large-scale, prospective, observational study of leukocytapheresis for ulcerative colitis: treatment outcomes of 847 patients in clinical practice. J Crohns Colitis. 2014;8:981–91.

    Article  Google Scholar 

  18. Sakuraba A, Motoya S, Watanabe K, et al. An open-label prospective randomized multicenter study shows very rapid remission of ulcerative colitis by intensive granulocyte and monocyte adsorptive apheresis as compared with routine weekly treatment. Am J Gastroenterol. 2009;104:2990–5.

    Article  Google Scholar 

  19. Fukunaga K, Yokoyama Y, Kamokozuru K, et al. Adsorptive granulocyte/monocyte apheresis for the maintenance of remission in patients with ulcerative colitis: a prospective randomized, double blind, sham-controlled clinical trial. Gut Liver. 2012;6:427–33.

    CAS  Article  Google Scholar 

  20. Sakuraba A, Sato T, Morohoshi Y, et al. Intermittent granulocyte and monocyte apheresis versus mercaptopurine for maintaining remission of ulcerative colitis: a pilot study. Ther Apher Dial. 2012;16:213–8.

    CAS  Article  Google Scholar 

  21. Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med. 1987;317:1625–9.

  22. Frøslie KF, Jahnsen J, Moum BA, et al. Endoscopic remission in inflammatory bowel disease: results from a Norwegian population-based cohort. Gastroenterology. 2007;133:412–22.

    Article  Google Scholar 

  23. Ardizzone S, Cassinotti A, Duca P, et al. Mucosal healing predicts late outcomes after the first course of corticosteroids for newly diagnosed ulcerative colitis. Clin Gastroenterol Hepatol. 2011;9(483):489.

    Google Scholar 

  24. Colombel JF, Rutgeerts P, Reinisch W, et al. Early endoscopic remission with infliximab is associated with improved long-term clinical outcomes in ulcerative colitis. Gastroenterology. 2011;141:1194–201.

    CAS  Article  Google Scholar 

  25. Yokoyama K, Kobayashi K, Mukae M, et al. Clinical study of the relation between endoscopic remission and long-term outcomes in ulcerative colitis. Gastroenterol Res Pract. 2013;2013:192794.

    Article  Google Scholar 

  26. Arai M, Naganuma M, Sugimoto S, et al. The ulcerative colitis endoscopic index of severity is useful to predict medium- to long-term prognosis in ulcerative colitis patients with clinical remission. J Crohns Colitis. 2016;10:1303–9.

    Article  Google Scholar 

  27. Komoto S, Matsuoka K, Kobayashi T, et al. Safety and efficacy of leukocytapheresis in elderly patients with ulcerative colitis: The impact in steroid-free elderly patients. J Gastroenterol Hepatol. 2018;33:1485–91.

    CAS  Article  Google Scholar 

  28. Naganuma M, Sakuraba A, Hibi T. Ulcerative colitis: prevention of relapse. Expert Rev Gastroenterol Hepatol. 2013;7:341–51.

    CAS  Article  Google Scholar 

  29. Takayama T, Kanai T, Matsuoka K, et al. Long-term prognosis of patients with ulcerative colitis treated with cytapheresis therapy. J Crohns Colitis. 2013;7:e49–54.

    Article  Google Scholar 

Download references


We would like to thank the late Professor Takayuki Matsumoto (Hyogo College of Medicine) for his significant contribution to the study protocol. We would also like to thank Editage ( for English language editing and Dr. Kiyoso Yamataga (Kureha Special Laboratory, Tokyo, Japan) for the statistical analysis. Members in the CAPTAIN Study Group are Makoto Naganuma, Shinya Sugimoto, Kosaku Nanki, Shinta Mizuno, Haruhiko Ogata, Takanori Kanai (Keio University School of Medicine), Yoko Yokoyama, Kenji Watanabe, Kazuko Nagase, Shiro Nakamura (Hyogo College of Medicine), Satoshi Motoya, Hiroki Tanaka, Masanao Nasuno, Maki Miyagawa (Sapporo Kosei General Hospital), Koji Sawada (Dojima General and Gastroenterology Clinic), Fumito Hirai (Fukuoka University Chikushi Hospital), Takayuki Yamamoto, Takahiro Shimoyama (Yokkaichi Hazu Medical Center), Kentaro Ikeya, Hiroyuki Hanai (Hamamatsu South Hospital), Ayumi Itoh, Teppei Omori (Tokyo Women’s Medical University), Kaoru Yokoyama (Kitasato University), Keiichi Mitsuyama, Hiroshi Yamazaki (Kurume University School of Medicine), Yasuhisa Sakata (Saga Universtiy), Naoki Yoshimura (Tokyo Yamate Medical Center), Takayuki Shirai (Tokai University Hachioji Hospital), Yasuo Suzuki (Toho University Sakura Medical Center), Minoru Matsuura (Kyoto University), Shinji Tanaka, Kohei Hayashi, Yositaka Ueno (Hiroshima University), Ryosuke Sakemi (Tobata Kyoritsu Hospital), Yo Ishiguro (Hirosaki National Hospital), Atsushi Yoshida, Yutaka Endo (Ofuna Chuo Hospital), Hirokazu Yamagami (Osaka City Universtiy), Toshiharu Sakurai (Kindai University), Masahiro Iwabuchi, Mikako Sugimura (Sendai Medical Center), Masahiro Iizuka (Akita Red Cross Hospital). Ko Nagino (Yamagata City Hospital Saiseikan), Taku Kobayashi, Toshifumi Hibi (Kitasato University Kitasato Institute Hospital), Kunio Ohnishi (Ikoma Clinic), Takuya Yoshino (Kitano Hospital), Toshihide Ohmori (Toshihide Ohmori Gastrointestinal Clinic), Tadashi Teramoto (Machida Gastrointestinal Hospital).


All investigators received non-financial support (provided with adacolumn® or cellsoba E.® for maintenance therapy) from JIMRO Co., Ltd and/or Asahi Kasei Medical, Co., Ltd. during the conduct of the study. However, the funding source was not involved in any part of the preparation of the research protocol, data analysis, and drafting of this manuscript.

Author information

Authors and Affiliations




TH conceived the study. MN, YY, KW, and TH designed the main concept of this study. MN, YY, KW drafted the main protocol. All authors participated in patient enrolment and clinical data acquisition. MN drafted and wrote the manuscript as the first version. TK and TH supervised the study. All authors contributed to critical review and approved the final draft.

Corresponding author

Correspondence to Makoto Naganuma.

Ethics declarations

Conflict of interest

Makoto Naganuma received commercial research funds from EA Pharma Co., Ltd. and Mochida Pharmaceutical Co., Ltd., outside the submitted work. Satoshi Motoya received consultant fees from Abbvie GK, Janssen Pharmaceutical K.K, Kyorin Pharmaceutical Co. Ltd, and Pfizer Japan Inc. and received lecture fees from Takeda Pharmaceutical Co., Ltd., Abbvie GK, Janssen Pharmaceutical K.K, Mistubishi Tanabe Pharma, and Mochida Pharmaceutical Co., Ltd., outside the submitted work. Fumihito Hirai received lecture fees from Abbvie GK, EA Pharma Co., Ltd, Mistubishi Tanabe Pharma, Janssen Pharmaceutical K.K., and Takeda Pharmaceutical Co., Ltd., outside the submitted work. Takanori Kanai received lecture fees from Mitsubishi Tanabe Pharma Corp, Astellas Pharma Inc, Miyarisan Pharmaceutical Co., Ltd. AstraZeneca Plc, EA Pharma Co., Ltd., Kyorin Pharmaceutical Co., Ltd. and commercial research funds from AbbVie GK,Mochida Pharmaceutical Co., Ltd.,Kyorin Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Mitsubishi Tanabe Pharma Corp, Takeda Pharmaceutical Co., Ltd., Nihon Kayaku, Yakult Honsha Co., Ltd.,Zeria Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Ono Pharmaceutical Co., Ltd., EA Pharma Co., Ltd., Ezaki Glico Co., Ltd., JIMRO Co., Ltd. and EN Otsuka Pharmaceutical Co., Ltd, outside the submitted work. Toshifumi Hibi received lecture fees from Mitsubishi Tanabe Pharma Corp, Abbvie GK, EA Pharma Co., Ltd., Janssen Pharmaceutical K.K., JIMRO Co. Ltd., Mochida Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Gilead Sciences Celltrion, Nihon Kayaku, Zeria Pharmaceutical Co., Ferring Pharmaceutical, Lilly Co., Ltd., Pfizer Japan Inc. outside the submitted work. All other authors have no competing interests to declare.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Naganuma, M., Yokoyama, Y., Motoya, S. et al. Efficacy of apheresis as maintenance therapy for patients with ulcerative colitis in an open-label prospective multicenter randomised controlled trial. J Gastroenterol 55, 390–400 (2020).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:


  • Granulocyte and monocyte adsorption apheresis
  • Leukocytapheresis ulcerative colitis
  • Maintenance therapy
  • Endoscopic remission