Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Clinical nutrition, enteral and parenteral nutrition

Concomitant use of enteral nutrition therapy is associated with sustained response to infliximab in patients with Crohn’s disease

European Journal of Clinical Nutrition volume 66, pages 1219–1223 (2012)Cite this article

Subjects

Abstract

Background/Objectives:

A significant proportion of Crohn’s disease (CD) patients receiving infliximab (IFX) maintenance therapy show loss of responsiveness despite a good initial response. The factors other than immunomodulators that prevent IFX dose escalation have yet to be fully elucidated. This study was performed to identify clinical factors or concomitant therapies associated with sustained response to IFX.

Subjects/Methods:

Seventy-four consecutive CD patients who had successful IFX induction therapy between 2002 and 2010 underwent IFX maintenance therapy. Patients showing loss of response to IFX were treated with IFX intensification therapy. Factors involved in the sustained response to IFX were investigated retrospectively.

Results:

After a median follow-up of 85 weeks, loss of response to IFX was observed in 30 (40.5%) cases. On logistic regression analysis, concomitant use of enteral nutrition (EN) therapy (elemental and/or polymeric formulas) was identified as an independent factor associated with sustained response to IFX. Receiver operating characteristic curve analysis indicated a cutoff value of 600 kcal/day. We divided the patients into the ‘EN group’ (⩾600 kcal/day) and ‘control group’ (<600 kcal/day). The cumulative number of loss of response was significantly lower in the EN group (odds ratio: 0.23, P=0.0043). Kaplan–Meier analysis confirmed the significantly lower rate of loss of response in the EN group (P=0.013). Multivariate hazard ratio was 0.37 (P=0.025). Type of EN formula did not affect the results.

Conclusions:

Concomitant use of EN ⩾600 kcal/day is likely to yield a sustained response to IFX in CD patients.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Khor B, Gardet A, Xavier RJ . Genetics and pathogenesis of inflammatory bowel disease. Nature 2011; 474: 307–317.

    Article  CAS  Google Scholar 

  2. Maloy KJ, Powrie F . Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature 2011; 474: 298–306.

    Article  CAS  Google Scholar 

  3. Strober W, Fuss IJ . Proinflammatory cytokines in the pathogenesis of inflammatory bowel diseases. Gastroenterology 2011; 140: 1756–1767.

    Article  CAS  Google Scholar 

  4. Burger D, Travis S . Conventional medical management of inflammatory bowel disease. Gastroenterology 2011; 140: 1827–1837. ; e1822.

    Article  Google Scholar 

  5. Danese S, Colombel JF, Reinisch W, Rutgeerts PJ . Review article: infliximab for Crohn’s disease treatment—shifting therapeutic strategies after 10 years of clinical experience. Aliment Pharmacol Ther 2011; 33: 857–869.

    Article  CAS  Google Scholar 

  6. Targan SR, Hanauer SB, van Deventer SJ, Mayer L, Present DH, Braakman T et al. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn’s disease. Crohn’s Disease cA2 Study Group. N Engl J Med 1997; 337: 1029–1035.

    Article  CAS  Google Scholar 

  7. Hanauer SB, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet 2002; 359: 1541–1549.

    Article  CAS  Google Scholar 

  8. Sands BE, Anderson FH, Bernstein CN, Chey WY, Feagan BG, Fedorak RN et al. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med 2004; 350: 876–885.

    Article  CAS  Google Scholar 

  9. Gisbert JP, Panes J . Loss of response and requirement of infliximab dose intensification in Crohn’s disease: a review. Am J Gastroenterol 2009; 104: 760–767.

    Article  CAS  Google Scholar 

  10. Ben-Horin S, Chowers Y . Review article: loss of response to anti-TNF treatments in Crohn’s disease. Aliment Pharmacol Ther 2011; 33: 987–995.

    Article  CAS  Google Scholar 

  11. Danese S, Fiorino G, Reinisch W . Review article: Causative factors and the clinical management of patients with Crohn’s disease who lose response to anti-TNF-alpha therapy. Aliment Pharmacol Ther 2011; 34: 1–10.

    Article  CAS  Google Scholar 

  12. Colombel JF, Sandborn WJ, Reinisch W, Mantzaris GJ, Kornbluth A, Rachmilewitz D et al. Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med 2010; 362: 1383–1395.

    Article  CAS  Google Scholar 

  13. Vermeire S, Noman M, Van Assche G, Baert F, D’Haens G, Rutgeerts P . Effectiveness of concomitant immunosuppressive therapy in suppressing the formation of antibodies to infliximab in Crohn’s disease. Gut 2007; 56: 1226–1231.

    Article  CAS  Google Scholar 

  14. Schnitzler F, Fidder H, Ferrante M, Noman M, Arijs I, Van Assche G et al. Long-term outcome of treatment with infliximab in 614 patients with Crohn’s disease: results from a single-centre cohort. Gut 2009; 58: 492–500.

    Article  CAS  Google Scholar 

  15. Kopylov U, Mantzaris GJ, Katsanos KH, Reenaers C, Ellul P, Rahier JF et al. The efficacy of shortening the dosing interval to once every six weeks in Crohn’s patients losing response to maintenance dose of infliximab. Aliment Pharmacol Ther 2011; 33: 349–357.

    Article  CAS  Google Scholar 

  16. Yao T, Matsui T, Hiwatashi N . Crohn’s disease in Japan: diagnostic criteria and epidemiology. Dis Colon Rectum 2000; 43: S85–S93.

    Article  CAS  Google Scholar 

  17. Tanaka T, Takahama K, Kimura T, Mizuno T, Nagasaka M, Iwata K et al. Effect of concurrent elemental diet on infliximab treatment for Crohn’s disease. J Gastroenterol Hepatol 2006; 21: 1143–1149.

    Article  CAS  Google Scholar 

  18. Goh J, O’Morain CA . Review article: nutrition and adult inflammatory bowel disease. Aliment Pharmacol Ther 2003; 17: 307–320.

    Article  CAS  Google Scholar 

  19. Griffiths AM . Enteral nutrition in the management of Crohn’s disease. J Parenter Enteral Nutr 2005; 29: S108–S112. discussion S112–107, S184–108.

    Article  Google Scholar 

  20. Lochs H . Enteral nutrition-the new maintenance therapy in Crohn’s disease? Inflamm Bowel Dis 2007; 13: 1581–1582.

    Article  Google Scholar 

  21. Rigaud D, Cosnes J, Le Quintrec Y, Rene E, Gendre JP, Mignon M . Controlled trial comparing two types of enteral nutrition in treatment of active Crohn’s disease: elemental versus polymeric diet. Gut 1991; 32: 1492–1497.

    Article  CAS  Google Scholar 

  22. Verma S, Brown S, Kirkwood B, Giaffer MH . Polymeric versus elemental diet as primary treatment in active Crohn’s disease: a randomized, double-blind trial. Am J Gastroenterol 2000; 95: 735–739.

    Article  CAS  Google Scholar 

  23. Ameho CK, Adjei AA, Harrison EK, Takeshita K, Morioka T, Arakaki Y et al. Prophylactic effect of dietary glutamine supplementation on interleukin 8 and tumour necrosis factor alpha production in trinitrobenzene sulphonic acid induced colitis. Gut 1997; 41: 487–493.

    Article  CAS  Google Scholar 

  24. Tsune I, Ikejima K, Hirose M, Yoshikawa M, Enomoto N, Takei Y et al. Dietary glycine prevents chemical-induced experimental colitis in the rat. Gastroenterology 2003; 125: 775–785.

    Article  CAS  Google Scholar 

  25. Andou A, Hisamatsu T, Okamoto S, Chinen H, Kamada N, Kobayashi T et al. Dietary histidine ameliorates murine colitis by inhibition of proinflammatory cytokine production from macrophages. Gastroenterology 2009; 136: 564–574. ; e562.

    Article  CAS  Google Scholar 

  26. Johnson T, Macdonald S, Hill SM, Thomas A, Murphy MS . Treatment of active Crohn’s disease in children using partial enteral nutrition with liquid formula: a randomised controlled trial. Gut 2006; 55: 356–361.

    Article  CAS  Google Scholar 

  27. Korelitz BI . The role of liquid diet in the management of small bowel Crohn’s disease. Inflamm Bowel Dis 2000; 6: 66–67. ; discussion 68–69.

    Article  CAS  Google Scholar 

  28. Hirakawa H, Fukuda Y, Tanida N, Hosomi M, Shimoyama T . Home elemental enteral hyperalimentation (HEEH) for the maintenance of remission in patients with Crohn’s disease. Gastroenterol Jpn 1993; 28: 379–384.

    Article  CAS  Google Scholar 

  29. Fukuda Y, Kosaka T, Okui M, Hirakawa H, Shimoyama T . Efficacy of nutritional therapy for active Crohn’s disease. J Gastroenterol 1995; 30 (Suppl 8), 83–87.

    PubMed  Google Scholar 

  30. Takagi S, Utsunomiya K, Kuriyama S, Yokoyama H, Takahashi S, Iwabuchi M et al. Effectiveness of an ‘half elemental diet’ as maintenance therapy for Crohn’s disease: a randomized-controlled trial. Aliment Pharmacol Ther 2006; 24: 1333–1340.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Atsushi Isono, Hirotsugu Uehara, Yasutaka Kato, Kiyoshi Furukawa, Kazuki Hatakeyama, Shin-ichiro Takeda, Yasushi Mandai, Tomoo Makita, Yoshie Takahashi and Yuhoko Furuya (Department of Gastroenterology and Hepatology, Chiba University Hospital, Japan) for their clinical assistance.

Author information

Authors and Affiliations

  1. Department of Medicine and Clinical Oncology (K1), Graduate School of Medicine, Chiba University, Chiba-shi, Japan

    S Sazuka, T Katsuno, T Nakagawa, M Saito, K Saito, T Matsumura, M Arai, T Sato & O Yokosuka

Authors
  1. S Sazuka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T Katsuno
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T Nakagawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M Saito
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K Saito
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. T Matsumura
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M Arai
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. T Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. O Yokosuka
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T Katsuno.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sazuka, S., Katsuno, T., Nakagawa, T. et al. Concomitant use of enteral nutrition therapy is associated with sustained response to infliximab in patients with Crohn’s disease. Eur J Clin Nutr 66, 1219–1223 (2012). https://doi.org/10.1038/ejcn.2012.120

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ejcn.2012.120

Keywords

This article is cited by

Search

Advanced search

Quick links