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Lower Risk of B1-to-pB3-Stage Migration in Crohn’s Disease Upon Immunosuppressive and Anti-TNF Treatment in the Swiss IBD Cohort Study

  • Patrick S. CernochEmail author
  • Nicolas Fournier
  • Jonas Zeitz
  • Michael Scharl
  • Bernhard Morell
  • Thomas Greuter
  • Philipp Schreiner
  • Benjamin Misselwitz
  • Ekaterina Safroneeva
  • Alain M. Schoepfer
  • Stephan R. Vavricka
  • Gerhard Rogler
  • Luc Biedermann
  • Swiss IBD Cohort Study Group
Original Article
  • 39 Downloads

Abstract

Background

While the long-term evolution of disease behavior in Crohn’s disease has been well described in the pre-anti-TNF era, our knowledge thereon remains scarce after the introduction of anti-TNF.

Aims

Our investigation examined the long-term evolution of disease concerning Montreal classification’s B-stages over time in patients enrolled into the Swiss IBD Cohort Study between 2006 and 2017.

Methods

We analyzed prospectively collected SIBDCS data using a Markov model and multivariate testing for effects of treatment and other confounders on B-stage migration over time. The primary outcome was a transition in disease behavior from B1 to either B2 or pB3, or from B2 to pB3, respectively.

Results

The 10- and 15-year probability of remaining in B1 was 0.61 and 0.48, as opposed to a probability to migrate to B2 or B3 of 0.25 or 0.14, and 0.32 or 0.2, after 10 and 15 years, respectively. In multivariate testing, the hazard ratio for migrating from B1 to pB3 (HR 0.27) and from B2 to pB3 (HR 0.12) was lower in patients > 40 years compared to patients < 17 years. We found that immunosuppression (HR 0.38) and treatment with anti-TNF for > 1 year (HR 0.30) were associated with a decreased likelihood of transitioning from stage B1 to pB3.

Conclusions

While in the anti-TNF era most patients with Crohn’s disease will eventually develop stricturing and/or penetrating complications, our data indicate that immunosuppressive and anti-TNF treatment for more than 1 year reduce the risk of transitioning from stage B1 to pB3 in the long-term run.

Keywords

Crohn’s disease Tumor necrosis factor-alpha Immunosuppressive agents Montreal classification Disease-modifying 

Notes

Acknowledgments

The authors would like to thank the patients enrolled in the SIBDCS for their commitment to promoting research.

Members of the SIBDCS study group: Claudia Anderegg; Peter Bauerfeind; Christoph Beglinger; Stefan Begré; Dominique Belli; José M. Bengoa; Luc Biedermann; Beat Bigler; Janek Binek; Mirjam Blattmann; Stephan Boehm; Jan Borovicka; Christian P. Braegger; Nora Brunner; Patrick Bühr; Bernard Burnand; Emanuel Burri; Sophie Buyse; Matthias Cremer; Dominique H. Criblez; Philippe de Saussure; Lukas Degen; Joakim Delarive; Christopher Doerig; Barbara Dora; Gian Dorta; Mara Egger; Tobias Ehmann; Ali El-Wafa; Matthias Engelmann; Jessica Ezri; Christian Felley; Markus Fliegner; Nicolas Fournier; Montserrat Fraga; Pascal Frei; Remus Frei; Michael Fried; Florian Froehlich; Christian Funk; Raoul Ivano Furlano; Suzanne Gallot-Lavallée; Martin Geyer; Marc Girardin; Delphine Golay; Tanja Grandinetti; Beat Gysi; Horst Haack; Johannes Haarer; Beat Helbling; Peter Hengstler; Denise Herzog; Cyrill Hess; Klaas Heyland; Thomas Hinterleitner; Philippe Hiroz; Claudia Hirschi; Petr Hruz; Rika Iwata; Res Jost; Pascal Juillerat; Vera Kessler Brondolo; Christina Knellwolf; Christoph Knoblauch; Henrik Köhler; Rebekka Koller; Claudia Krieger-Grübel; Gerd Kullak-Ublick; Patrizia Künzler; Markus Landolt; Rupprecht Lange; Frank Serge Lehmann; Andrew Macpherson; Philippe Maerten; Michel H. Maillard; Christine Manser; Michael Manz; Urs Marbet; George Marx; Christoph Matter; Valérie McLin; Rémy Meier; Martina Mendanova; Christa Meyenberger; Pierre Michetti; Benjamin Misselwitz; Darius Moradpour; Bernhard Morell; Patrick Mosler; Christian Mottet; Christoph Müller; Pascal Müller; Beat Müllhaupt; Claudia Münger-Beyeler; Leilla Musso; Andreas Nagy; Michaela Neagu; Cristina Nichita; Jan Niess; Natacha Noël; Andreas Nydegger; Nicole Obialo; Carl Oneta; Cassandra Oropesa; Ueli Peter; Daniel Peternac; Laetitia Marie Petit; Franziska Piccoli-Gfeller; Julia Beatrice Pilz; Valérie Pittet; Nadia Raschle; Ronald Rentsch; Sophie Restellini; Jean-Pierre Richterich; Sylvia Rihs; Marc Alain Ritz; Jocelyn Roduit; Daniela Rogler; Gerhard Rogler; Jean-Benoît Rossel; Markus Sagmeister; Gaby Saner; Bernhard Sauter; Mikael Sawatzki; Michela Schäppi; Michael Scharl; Martin Schelling; Susanne Schibli; Hugo Schlauri; Sybille Schmid Uebelhart; Jean-François Schnegg; Alain Schoepfer; Frank Seibold; Mariam Seirafi; Gian-Marco Semadeni; David Semela; Arne Senning; Marc Sidler; Christiane Sokollik; Johannes Spalinger; Holger Spangenberger; Philippe Stadler; Michael Steuerwald; Alex Straumann; Bigna Straumann-Funk; Michael Sulz; Joël Thorens; Sarah Tiedemann; Radu Tutuian; Stephan Vavricka; Francesco Viani; Jürg Vögtlin; Roland Von Känel; Alain Vonlaufen; Dominique Vouillamoz; Rachel Vulliamy; Jürg Wermuth; Helene Werner; Paul Wiesel; Reiner Wiest; Tina Wylie; Jonas Zeitz; Dorothee Zimmermann.

Funding

This work was supported by grants from the Swiss National Science Foundation (SNF) to Gerhard Rogler [the Swiss IBD Cohort (Grant No. 3347CO-108792)].

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Ekbom A, Helmick CG, Zack M, Holmberg L, Adami HO. Survival and causes of death in patients with inflammatory bowel disease: a population-based study. Gastroenterology. 1992;103:954–960.CrossRefGoogle Scholar
  2. 2.
    Hovde O, Kempski-Monstad I, Smastuen MC, et al. Mortality and causes of death in Crohn’s disease: results from 20 years of follow-up in the IBSEN study. Gut. 2014;63:771–775.CrossRefGoogle Scholar
  3. 3.
    Jess T, Winther KV, Munkholm P, Langholz E, Binder V. Mortality and causes of death in Crohn’s disease: follow-up of a population-based cohort in Copenhagen County, Denmark. Gastroenterology. 2002;122:1808–1814.CrossRefGoogle Scholar
  4. 4.
    Floyd DN, Langham S, Séverac HC, Levesque BG. The economic and quality-of-life burden of Crohn’s disease in Europe and the United States, 2000 to 2013: a systematic review. Dig Dis Sci. 2015;60:299–312.  https://doi.org/10.1007/s10620-014-3368-z.CrossRefPubMedGoogle Scholar
  5. 5.
    Sachar D, Andrews H, Farmer R, et al. Proposed classification of patient subgroups in Crohn’s disease. Gastroenterol Int. 1992;5:141–154.Google Scholar
  6. 6.
    Van Assche G, Dignass A, Panes J, et al. The second European evidence-based Consensus on the diagnosis and management of Crohn’s disease: definitions and diagnosis. J Crohns Colitis. 2010;4:7–27.CrossRefGoogle Scholar
  7. 7.
    Cosnes J, Cattan S, Blain A, et al. Long-term evolution of disease behavior of Crohn’s disease. Inflamm Bowel Dis. 2002;8:244–250.CrossRefGoogle Scholar
  8. 8.
    Louis E, Collard A, Oger AF, Degroote E, Aboul NasrElYafi FA, Belaiche J. Behaviour of Crohn’s disease according to the Vienna classification: changing pattern over the course of the disease. Gut. 2001;49:777–782.CrossRefGoogle Scholar
  9. 9.
    Polito JM 2nd, Childs B, Mellits ED, Tokayer AZ, Harris ML, Bayless TM. Crohn’s disease: influence of age at diagnosis on site and clinical type of disease. Gastroenterology. 1996;111:580–586.CrossRefGoogle Scholar
  10. 10.
    Beaugerie L, Seksik P, Nion-Larmurier I, Gendre JP, Cosnes J. Predictors of Crohn’s disease. Gastroenterology. 2006;130:650–656.CrossRefGoogle Scholar
  11. 11.
    Biedermann L, Fournier N, Misselwitz B, et al. High rates of smoking especially in female Crohn’s disease patients and low use of supportive measures to achieve smoking cessation-data from the Swiss IBD Cohort Study. J Crohns Colitis. 2015;9:819–829.CrossRefGoogle Scholar
  12. 12.
    Lang BM, Biedermann L, van Haaften WT, et al. Genetic polymorphisms associated with smoking behaviour predict the risk of surgery in patients with Crohn’s disease. Aliment Pharmacol Ther. 2018;47:55–66.CrossRefGoogle Scholar
  13. 13.
    Annese V, Duricova D, Gower-Rousseau C, Jess T, Langholz E. Impact of new treatments on hospitalisation, surgery, infection, and mortality in IBD: a focus paper by the Epidemiology Committee of ECCO. J Crohns Colitis. 2016;10:216–225.CrossRefGoogle Scholar
  14. 14.
    Gower-Rousseau C, Vasseur F, Fumery M, et al. Epidemiology of inflammatory bowel diseases: new insights from a French population-based registry (EPIMAD). Dig Liver Dis. 2013;45:89–94.CrossRefGoogle Scholar
  15. 15.
    Gower-Rousseau C, Savoye G, Colombel JF, Peyrin-Biroulet L. Are we improving disease outcomes in IBD? A view from the epidemiology side. Gut. 2014;63:1529–1530.CrossRefGoogle Scholar
  16. 16.
    Nguyen GC, Nugent Z, Shaw S, Bernstein CN. Outcomes of patients with Crohn’s disease improved from 1988 to 2008 and were associated with increased specialist care. Gastroenterology. 2011;141:90–97.CrossRefGoogle Scholar
  17. 17.
    Magro F, Rodrigues-Pinto E, Coelho R, et al. Is it possible to change phenotype progression in Crohn’s disease in the era of immunomodulators? Predictive factors of phenotype progression. Am J Gastroenterol. 2014;109:1026–1036.CrossRefGoogle Scholar
  18. 18.
    Jeuring SF, van den Heuvel TR, Liu LY, 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;112:325–336.CrossRefGoogle Scholar
  19. 19.
    Magro F, Portela F. Management of inflammatory bowel disease with infliximab and other anti-tumor necrosis factor alpha therapies. BioDrugs. 2010;24:3–14.CrossRefGoogle Scholar
  20. 20.
    Ferges W, Rampertab SD, Shafqet M, et al. Experience with anti-TNF-α biologic agents in succession in patients with Crohn’s disease: a retrospective analysis of a single center. J Clin Gastroenterol. 2016;50:326–330.CrossRefGoogle Scholar
  21. 21.
    Feagan BG, Panaccione R, Sandborn WJ, et al. Effects of adalimumab therapy on incidence of hospitalization and surgery in Crohn’s disease: results from the CHARM study. Gastroenterology. 2008;135:1493–1499.CrossRefGoogle Scholar
  22. 22.
    Jeuring S, Van den Heuvel T, Zeegers M, et al. 79 Disease behavior in Crohn’s disease patients diagnosed in the biological era: a Dutch population-based IBD-SL Cohort Study. Gastroenterology. 2015;148:S-22.CrossRefGoogle Scholar
  23. 23.
    Pittet V, Juillerat P, Mottet C, et al. Cohort profile: the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS). Int J Epidemiol. 2009;38:922–931.CrossRefGoogle Scholar
  24. 24.
    Herzog D, Fournier N, Buehr P, et al. Prevalence of intestinal complications in inflammatory bowel disease: a comparison between paediatric-onset and adult-onset patients. Eur J Gastroenterol Hepatol. 2017;29:926–931.CrossRefGoogle Scholar
  25. 25.
    Manser CN, Frei P, Grandinetti T, et al. Risk factors for repetitive ileocolic resection in patients with Crohn’s disease: results of an observational cohort study. Inflamm Bowel Dis. 2014;20:1548–1554.CrossRefGoogle Scholar
  26. 26.
    Safroneeva E, Vavricka SR, Fournier N, et al. Impact of the early use of immunomodulators or TNF antagonists on bowel damage and surgery in Crohn’s disease. Aliment Pharmacol Ther. 2015;42:977–989.CrossRefGoogle Scholar
  27. 27.
    Vavricka SR, Brun L, Ballabeni P, et al. Frequency and risk factors for extraintestinal manifestations in the Swiss inflammatory bowel disease cohort. Am J Gastroenterol. 2011;106:110–119.CrossRefGoogle Scholar
  28. 28.
    Jackson C. Multi-state models for panel data: the MSM package for R. J Stat Softw. 2011;2011:28.Google Scholar
  29. 29.
    Cosnes J, Gower-Rousseau C, Seksik P, Cortot A. Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology. 2011;140:1785–1794.CrossRefGoogle Scholar
  30. 30.
    Camus M, Seksik P, Bourrier A, et al. Long-term outcome of patients with Crohn’s disease who respond to azathioprine. Clin Gastroenterol Hepatol. 2013;11:389–394.CrossRefGoogle Scholar
  31. 31.
    Cosnes J, Bourrier A, Nion-Larmurier I, Sokol H, Beaugerie L, Seksik P. Factors affecting outcomes in Crohn’s disease over 15 years. Gut. 2012;61:1140–1145.CrossRefGoogle Scholar
  32. 32.
    Kugathasan S, Denson LA, Walters TD, et al. Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study. Lancet. 2017;389:1710–1718.CrossRefGoogle Scholar
  33. 33.
    Targownik LE, Leung S, Lix LM, Singh H, Bernstein CN. Persistence with immunomodulator monotherapy use and incidence of therapeutic ineffectiveness among users of immunomodulator monotherapy in IBD. Am J Gastroenterol. 2018;113:1206–1216.CrossRefGoogle Scholar
  34. 34.
    Cosnes J, Bourrier A, Laharie D, et al. Early administration of azathioprine vs conventional management of Crohn’s Disease: a randomized controlled trial. Gastroenterology. 2013;145:758–765.CrossRefGoogle Scholar
  35. 35.
    Panés J, López-Sanromán A, Bermejo F, et al. Early azathioprine therapy is no more effective than placebo for newly diagnosed Crohn’s disease. Gastroenterology. 2013;145:e761.CrossRefGoogle Scholar
  36. 36.
    Frolkis AD, Dykeman J, Negrón ME, et al. Risk of surgery for inflammatory bowel diseases has decreased over time: a systematic review and meta-analysis of population-based studies. Gastroenterology. 2013;145:996–1006.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Patrick S. Cernoch
    • 1
    Email author
  • Nicolas Fournier
    • 2
  • Jonas Zeitz
    • 1
    • 6
  • Michael Scharl
    • 1
  • Bernhard Morell
    • 1
  • Thomas Greuter
    • 1
  • Philipp Schreiner
    • 1
  • Benjamin Misselwitz
    • 1
  • Ekaterina Safroneeva
    • 3
  • Alain M. Schoepfer
    • 4
  • Stephan R. Vavricka
    • 1
    • 5
  • Gerhard Rogler
    • 1
  • Luc Biedermann
    • 1
  • Swiss IBD Cohort Study Group
  1. 1.Division of Gastroenterology and Hepatology, Department of Gastroenterology, University Hospital Zurich (USZ)University of ZurichZurichSwitzerland
  2. 2.Institute of Social and Preventive Medicine (IUMSP)Lausanne University HospitalLausanneSwitzerland
  3. 3.Institute of Social and Preventive MedicineUniversity of BernBernSwitzerland
  4. 4.Division of Gastroenterology and Hepatology, Center Hospitalier Universitaire Vaudois (CHUV)University of LausanneLausanneSwitzerland
  5. 5.Center of Gastroenterology and HepatologyZurichSwitzerland
  6. 6.Center of GastroenterologyClinic HirslandenZurichSwitzerland

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