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Anti-tumor necrosis factor therapy decreases the risk of initial intestinal surgery after diagnosis of Crohn’s disease of inflammatory type

  • Original Article—Alimentary Tract
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Abstract

Background

Anti-tumor necrosis factor (TNF) therapy induces and maintains clinical remission in patients with Crohn’s disease (CD). However, the effect of anti-TNF therapy on the natural course of CD remains controversial. We aimed to investigate the effect of anti-TNF therapy on the initial intestinal surgery for CD.

Methods

In this single-center retrospective cohort study, clinical course of 199 CD patients of inflammatory type at the initial diagnosis (the period between 1973 and 2014) was precisely reviewed until the end of 2016. Patients were divided into TNF and non-TNF groups based on anti-TNF agent use. After comparisons of clinical characteristics and medical treatments, propensity scores were calculated for covariates. Risk of intestinal surgery was compared by a Cox proportional hazards model using the propensity scores. The effect of immunomodulators on initial intestinal surgery was assessed in the TNF group.

Results

During the study period, 108 patients received anti-TNF therapy. The patients in the TNF group were diagnosed more recently, and more frequently had isolated colonic involvement, and perianal disease. Immunomodulators were more frequently used in the TNF group. Cumulative probability of initial intestinal surgery was significantly lower in the TNF group (P < 0.0001). The hazard ratio in the TNF group was 0.32 (95% CI 0.13–0.74). Immunomodulators did not decrease the risk of initial intestinal surgery.

Conclusions

Anti-TNF therapy can decrease the risk of intestinal surgery among patients with inflammatory-type CD at the initial diagnosis. Further studies should be necessary to determine the additive effect of immunomodulators on the risk of intestinal surgery.

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Abbreviations

CD:

Crohn’s disease

TNF:

Tumor necrosis factor

IFX:

Infliximab

ADA:

Adalimumab

IBD:

Inflammatory bowel disease

AZA:

Azathioprine

6MP:

6-Mercaptopurine

ED:

Elemental diet

References

  1. Pariente B, Cosnes J, Danese S, et al. Development of the Crohn’s disease digestive damage score, the Lémann score. Inflamm Bowel Dis. 2011;17:1415–22.

    Article  PubMed  Google Scholar 

  2. Bernell O, Lapidus A, Hellers G. Risk factors for surgery and postoperative recurrence in Crohn’s disease. Ann Surg. 2000;231:38–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Oriuchi T, Hiwatashi N, Kinouchi Y, et al. Clinical course and longterm prognosis of Japanese patients with Crohn’s disease: predictive factors, rates of operation, and mortality. J Gastroenterol. 2003;38:942–53.

    Article  PubMed  Google Scholar 

  4. Ramadas AV, Gunesh S, Thomas GAO, et al. Natural history of Crohn’s disease in a population-based cohort from Cardiff (1986–2003): a study of changes in medical treatment and surgical resection rates. Gut. 2010;59:1200–6.

    Article  CAS  PubMed  Google Scholar 

  5. Rungoe C, Langholz E, Andersson M, et al. Changes in medical treatment and surgery rates in inflammatory bowel disease: a nationwide cohort study 1979–2011. Gut. 2014;63:1607–16.

    Article  CAS  PubMed  Google Scholar 

  6. Shi H, Ng S. The state of the art on treatment of Crohn’s disease. J Gastroenterol. 2018;53:989–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Targan S, Hanauer S, van Deventer S, 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;337:1029–35.

    Article  CAS  PubMed  Google Scholar 

  8. Colombel J, Sandborn W, Rutgeerts P, et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial. Gastroenterology. 2007;132:52–65.

    Article  CAS  PubMed  Google Scholar 

  9. Peyrin-Biroulet L, Oussalah A, Williet N, et al. Impact of azathioprine and tumour necrosis factor antagonists on the need for surgery in newly diagnosed Crohn’s disease. Gut. 2011;60:930–6.

    Article  CAS  PubMed  Google Scholar 

  10. Mao E, Hazlewood G, Kaplan G, et al. Systematic review with meta-analysis: comparative efficacy of immunosuppressants and biologics for reducing hospitalization and surgery in Crohn’s disease and ulcerative colitis. Aliment Pharmacol Ther. 2017;45:3–13.

    Article  CAS  PubMed  Google Scholar 

  11. Vernier-Massouille G, Balde M, Salleron J, et al. Natural history of pediatric Crohn’s disease: a population-based cohort study. Gastroenterology. 2008;135:1106–13.

    Article  PubMed  Google Scholar 

  12. Jeuring S, van den Heuvel T, Liu L, et al. Improvements in the long-term outcome of Crohn’s disease over the past two decades and the relation to changes in medical management: results from the population-based IBDSL cohort. Am J Gastroenterol. 2017;112:325–36.

    Article  PubMed  Google Scholar 

  13. Satsangi J. The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut. 2006;55:749–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Peyrin-Biroulet L, Loftus E Jr, Colombel J, et al. Early Crohn disease: a proposed definition for use in disease-modification trials. Gut. 2010;59:141–7.

    Article  CAS  PubMed  Google Scholar 

  15. Rosenbaum P, Rubin DA. The central role of the propensity score in observational studies for causal effects. Biometrika. 1983;70:41–55.

    Article  Google Scholar 

  16. Rosenbaum P, Rubin D. Reducing bias in observational studies using subclassification on the propensity score. J Am Stat Assoc. 2012;79:516–24.

    Article  Google Scholar 

  17. Cosnes J, Cattan S, Blain A, et al. Long-term evolution of disease behavior of Crohn’s disease. Inflamm Bowel Dis. 2002;8:244–50.

    Article  PubMed  Google Scholar 

  18. Olaison G, Smedh K, Sjödahl R. Natural course of Crohn’s disease after ileocolic resection: endoscopically visualised ileal ulcers preceding symptoms. Gut. 1992;33:331–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. De Cruz P, Kamm MA, Prideaux L, et al. Postoperative recurrent luminal Crohn’s disease: a systematic review. Inflamm Bowel Dis. 2012;18:758–77.

    Article  PubMed  Google Scholar 

  20. Renna S, Cammà C, Modesto I, et al. Meta-analysis of the placebo rates of clinical relapse and severe endoscopic recurrence in postoperative Crohn’s disease. Gastroenterology. 2008;135:1500–9.

    Article  CAS  PubMed  Google Scholar 

  21. Frolkis A, Lipton D, Fiest K, et al. Cumulative incidence of second intestinal resection in Crohn’s disease: a systematic review and meta-analysis of population-based studies. Am J Gastroenterol. 2014;109:1739–48.

    Article  PubMed  Google Scholar 

  22. Rutgeerts P, Diamond R, Bala M, et al. Scheduled maintenance treatment with infliximab is superior to episodic treatment for the healing of mucosal ulceration associated with Crohn’s disease. Gastrointest Endosc. 2006;63:433–42.

    Article  PubMed  Google Scholar 

  23. Rutgeerts P, Van Assche G, Sandborn W, et al. Adalimumab induces and maintains mucosal healing in patients with Crohn’s disease: data from the EXTEND trial. Gastroenterology. 2012;142:1102–11.

    Article  CAS  PubMed  Google Scholar 

  24. Walters T, Kim M, Denson L, et al. Increased effectiveness of early therapy with anti-tumor necrosis factor-α vs an immunomodulator in children with Crohn’s disease. Gastroenterology. 2014;146:383–91.

    Article  CAS  PubMed  Google Scholar 

  25. D’Haens G, Baert F, van Assche G, et al. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn’s disease: an open randomized trial. Lancet. 2008;371:660–7.

    Article  CAS  PubMed  Google Scholar 

  26. Ferrante M, Colombel J, Sandborn W, et al. Validation of endoscopic activity scores in patients with Crohn’s disease based on a post hoc analysis of data from SONIC. Gastroenterology. 2013;145:978–86.

    Article  PubMed  Google Scholar 

  27. Shah S, Colombel J, Sands B, et al. Systematic review with meta-analysis: mucosal healing is associated with improved long-term outcomes in Crohn’s disease. Aliment Pharmacol Ther. 2016;43:317–33.

    Article  CAS  PubMed  Google Scholar 

  28. Burisch J, Pedersen N, Cukovic-Cavka S, et al. Initial disease course and treatment in an inflammatory bowel disease inception cohort in europe. Inflamm Bowel Dis. 2014;20:36–46.

    Article  PubMed  Google Scholar 

  29. Ng S, Zeng Z, Niewiadomski O, et al. Early Course of Inflammatory Bowel Disease in a Population-based Inception Cohort Study from 8 Countries in Asia and Australia. Gastroenterology. 2016;150:86–95.

    Article  PubMed  Google Scholar 

  30. Colombel J, Narula N, Peyrin-Biroulet L. Management strategies to improve outcomes of patients with inflammatory bowel diseases. Gastroenterology. 2017;152:351–61.

    Article  PubMed  Google Scholar 

  31. Lichtenstein G, Feagan B, Cohen R, et al. Drug therapies and the risk of malignancy in Crohn’s disease: results From the TREAT registry. Am J Gastroenterol. 2014;109:212–23.

    Article  CAS  PubMed  Google Scholar 

  32. Beaugerie L, Carrat F, Colombel J, et al. Risk of new or recurrent cancer under immunosuppressive therapy in patients with IBD and previous cancer. Gut. 2014;63:1416–23.

    Article  PubMed  Google Scholar 

  33. Ma C, Beilman C, Huang V, et al. Anti-TNF therapy within 2 Years of Crohn’s disease diagnosis improves patient outcomes: a retrospective cohort study. Inflamm Bowel Dis. 2016;22:870–9.

    Article  PubMed  Google Scholar 

  34. Peyrin-Biroulet L, Harmsen W, Tremaine W, et al. Surgery in a population-based cohort of Crohn’s disease from Olmsted County, Minnesota (1970–2004). Am J Gastroenterol. 2012;107:1693–701.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Colombel J, Sandborn W, Reinisch W, et al. Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med. 2010;362:1383–95.

    Article  CAS  PubMed  Google Scholar 

  36. Matsumoto T, Motoya S, Watanabe K, et al. Adalimumab monotherapy and a combination with azathioprine for Crohn’s disease: a prospective, randomized trial. J Crohns Colitis. 2016;10:1259–66.

    Article  PubMed  Google Scholar 

  37. Nakase H, Motoya S, Matsumoto T, et al. Significance of measurement of serum trough level and anti-drug antibody of adalimumab as personalized pharmacokinetics in patients with Crohn’s disease: a subanalysis of the DIAMOND trial. Aliment Pharmacol Ther. 2017;46:873–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Allez M, Lemann M, Bonnet J, et al. Long term outcome of patients with active Crohn’s disease exhibiting extensive and deep ulcerations at colonoscopy1. Am J Gastroenterol. 2002;97:947–53.

    PubMed  Google Scholar 

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Acknowledgements

The authors received generous statistical support from J. Kishimoto, a statistician at Kyushu University, Fukuoka, Japan.

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Authors and Affiliations

  1. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582, Japan

    Yutaka Nagata, Motohiro Esaki, Tomohiko Moriyama, Atsushi Hirano, Junji Umeno, Yuji Maehata, Takehiro Torisu & Takanari Kitazono

  2. Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Iwate Medical University, Morioka, Japan

    Takayuki Matsumoto

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  1. Yutaka Nagata
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  2. Motohiro Esaki
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  3. Tomohiko Moriyama
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  4. Atsushi Hirano
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  5. Junji Umeno
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  6. Yuji Maehata
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Correspondence to Motohiro Esaki.

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Conflict of interest

Motohiro Esaki received research grants from, Mitsubishi Tanabe Pharma (MTP), EA Pharma (EAP), AbbVie GK (AGK), ZERIA Pharma (ZP), and Asahi Kasei Medical (AKM), and lecture fee from MTP and AGK. Takayuki Matsumoto received research grants from MTP, EAP, and Nippon Kayaku, and lecture fee from MTP, EAP, KYORIN Pharma, AGK, Janssen Pharma, Mochida Pharma, Pfizer, ZP, and AstraZeneca, and advisory fee from JIMRO, Kissei Pharma, and Takeda Pharma (TP). Takanari Kitazono received research grants from Daiichi Sankyo (DS), TP, MTP, Astellas Pharma, Chugai Pharma, MSD, Boehringer Ingelheim, Bristol-Myers, Kyowa Hakko Kirin, AKM, Otsuka Pharma, and Torii Pharma, and lecture fee from DS. The remaining authors disclose no conflicts of interest. This study did not receive any financial support.

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Nagata, Y., Esaki, M., Moriyama, T. et al. Anti-tumor necrosis factor therapy decreases the risk of initial intestinal surgery after diagnosis of Crohn’s disease of inflammatory type. J Gastroenterol 54, 330–338 (2019). https://doi.org/10.1007/s00535-018-1511-x

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  • DOI: https://doi.org/10.1007/s00535-018-1511-x

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