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Earlier Anti-Tumor Necrosis Factor Therapy of Crohn’s Disease Correlates with Slower Progression of Bowel Damage

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Abstract

Introduction

Crohn’s disease (CD) follows a relapsing and remitting course incurring cumulative bowel damage over time. The question of whether or not the timing of the initiating biologic therapy affects long-term disease progression remains unanswered. Herein, we calculated rates of change in the Lémann index—which quantifies accumulated bowel damage—as a function of the time between the disease onset and initiation of biologic therapy. We aimed to explore the impact of the earlier introduction of biologics on the rate of progression of long-term cumulative bowel damage.

Methods

Medical records of CD patients treated during 2009–2014 at The Mount Sinai Hospital were queried. Inclusion criteria were two comprehensive assessments allowing calculation of the index at t1 and t2: two time-points ≥ 1 year apart. Patients with biologics introduced before or within 3 months at inclusion (t1) were defined as Bio-pre-t1 and those who did not as Bio-post-t1. The rate of disease progression was calculated as the change in the index per year during t1t2.

Results

A total of 88 patients were studied: 58 Bio-pre-t1 and 30 Bio-post-t1. Among the 58 Bio-pre-t1 cases, damage progressed in 29 (50%), regressed in 20 (34.5%), and stabilized in 9 (15.5%). Median time to initiation of biologics among patients whose index improved was nominally shorter compared to that in patients whose index progressed (8 vs. 15 years). Earlier introduction of biologics tended to correlate with the slower rate of progression (ρ = 0.241; p = 0.069).

Conclusions

Earlier introduction of biologics tended to correlate with the slower progression of bowel damage in CD, reflected by the reduced rate of Lémann index progression.

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References

  1. Wagtmans MJ, van Hogezand RA, Griffioen G, Verspaget HW, Lamers CB. Crohn’s disease of the upper gastrointestinal tract. Neth J Med. 1997;50:S2–S7.

    Article  CAS  Google Scholar 

  2. 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.

    Article  Google Scholar 

  3. Thia KT, Sandborn WJ, Harmsen WS, Zinsmeister AR, Loftus EV Jr. Risk factors associated with progression to intestinal complications of Crohn’s disease in a population-based cohort. Gastroenterology. 2010;139:1147–1155.

    Article  Google Scholar 

  4. Papi C, Festa V, Fagnani C, et al. Evolution of clinical behaviour in Crohn’s disease: predictive factors of penetrating complications. Dig Liver Dis. 2005;37:247–253.

    Article  CAS  Google Scholar 

  5. Rinawi F, Assa A, Hartman C, et al. Evolution of disease phenotype in pediatric-onset Crohn’s disease after more than 10 years follow up-Cohort study. Dig Liver Dis. 2016;48:1444–1450.

    Article  Google Scholar 

  6. Bhattacharya A, Rao BB, Koutroubakis IE, et al. Silent Crohn’s disease predicts increased bowel damage during multiyear follow-up: the consequences of under-reporting active inflammation. Inflamm Bowel Dis. 2016;22:2665–2671.

    Article  Google Scholar 

  7. Eder P, Michalak M, Katulska K, et al. Magnetic resonance enterographic predictors of one-year outcome in ileal and ileocolonic Crohn’s disease treated with anti-tumor necrosis factor antibodies. Sci Rep. 2015;5:10223.

    Article  Google Scholar 

  8. Pariente B, Mary J-Y, Danese S, et al. Development of the Lémann index to assess digestive tract damage in patients with Crohn’s disease. Gastroenterology. 2015;148:52–63.e3.

    Article  Google Scholar 

  9. Pariente B, Mary JY, Colombel JF, Cosnes J. Development of the Crohn’s disease (CD) digestive damage score: the Lémann score. J Crohn’s Colitis. 2013;7:S3.

    Article  Google Scholar 

  10. Amitai MM, Zarchin M, Lahat A, et al. Structural bowel damage in quiescent Crohn’s disease. Dig Liver Dis. 2017;49:490–494.

    Article  Google Scholar 

  11. Fiorino G, Bonifacio C, Allocca M, et al. Bowel damage as assessed by the Lémann index is reversible on anti-TNF therapy for Crohn’s disease. J Crohn’s Colitis. 2015;9:633–639.

    Article  Google Scholar 

  12. Fiorino G, Morin M, Bonovas S, et al. Prevalence of bowel damage assessed by cross-sectional imaging in early Crohn’s disease and its impact on disease outcome. J Crohn’s Colitis. 2016;11:274–280.

    Google Scholar 

  13. Kirchgesner J, Lemaitre M, Rudnichi A, et al. Therapeutic management of inflammatory bowel disease in real-life practice in the current era of anti-TNF agents: analysis of the French administrative health databases 2009–2014. Aliment Pharmacol Ther. 2017;45:37–49.

    Article  CAS  Google Scholar 

  14. Bouguen G, Levesque BG, Pola S, Evans E, Sandborn WJ. Endoscopic assessment and treating to target increase the likelihood of mucosal healing in patients with Crohn’s disease. Clin Gastroenterol Hepatol. 2014;12:978–985.

    Article  Google Scholar 

  15. Colombel JF, Sandborn WJ, Reinisch W, et al. Infliximab, azathioprine, or combination therapy for Crohn’s disease. N Engl J Med. 2010;362:1383–1395.

    Article  CAS  Google Scholar 

  16. Bodini G, Giannini EG, De Maria C, et al. Anti-TNF therapy is able to stabilize bowel damage progression in patients with Crohn’s disease. A study performed using the Lemann index. Dig Liver Dis. 2017;49:175–180.

    Article  CAS  Google Scholar 

  17. Sachar DB. Einstein, Darwin and conventional wisdom about Crohn’s disease. Dig Liver Dis. 2005;37:227–229.

    Article  CAS  Google Scholar 

  18. Bhagya Rao B, Koutroubakis IE, Ramos Rivers C, et al. Delineation of Crohn’s disease trajectories using change in Lemann index: a natural history study. J Clin Gastroenterol. 2016;50:476–482.

    Article  Google Scholar 

  19. Bhagya Rao B, Koutroubakis IE, Rivers CR, et al. Correlation of anemia status with worsening bowel damage as measured by Lemann index in patients with Crohn’s disease. Dig Liver Dis. 2016;48:626–631.

    Article  Google Scholar 

  20. Pellegatta G, Bodini G, Giannini EG, et al. Tu2009 does Lémann index reflect the quality of life in Crohn disease patients on treatment with biological therapy? Gastroenterology. 2016;150:S1004–S1005.

    Article  Google Scholar 

  21. Rao BB, Click BH, Koutroubakis IE, et al. The cost of Crohn’s disease: varied health care expenditure patterns across distinct disease trajectories. Inflamm Bowel Dis. 2017;23:107–115.

    Article  Google Scholar 

  22. Rutgeerts P, Van Assche G, Sandborn WJ, et al. Adalimumab induces and maintains mucosal healing in patients with Crohn’s disease: data from the EXTEND trial. Gastroenterology. 2012;142:1102–1111.e2.

    Article  CAS  Google Scholar 

  23. Schmidlin-Ren P, Reingold LJ, Broxson CS, et al. Anti-TNFα alters the natural history of experimental Crohn’s disease in rats when begun early, but not late, in disease. Am J Physiol Gastrointest Liver Physiol. 2016;311:G688–G698.

    Article  Google Scholar 

  24. Oh EH, Oh K, Han M, et al. Early anti-TNF/immunomodulator therapy is associated with better long-term clinical outcomes in Asian patients with Crohn’s disease with poor prognostic factors. PLOS ONE. 2017;12:e0177479.

    Article  Google Scholar 

  25. Ma C, Beilman CL, Huang VW, et al. Anti-TNF therapy within 2 years of Crohn’s disease diagnosis improves patient outcomes: a retrospective cohort study. Inflamm Bowel Dis. 2016;22:870–879.

    Article  Google Scholar 

  26. Ruel J, Ruane D, Mehandru S, Gower-Rousseau C, Colombel JF. IBD across the age spectrum: is it the same disease? Nat Rev Gastroenterol Hepatol. 2014;11:88–98.

    Article  Google Scholar 

  27. Fiorino G, Bonifacio C, Peyrin-Biroulet L, Danese S. Preventing collateral damage in Crohn’s disease: the Lémann index. J Crohn’s Colitis. 2016;10:495–500.

    Article  Google Scholar 

  28. Choi JH, Kim ES, Cho KB, et al. Old age at diagnosis is associated with favorable outcomes in Korean patients with inflammatory bowel disease. Intest Res. 2015;13:60–67.

    Article  Google Scholar 

Download references

Acknowledgment

We wish to acknowledge the energetic support of a cooperating group at Centre Hospitalier Régional Universitaire de Lille, France, including Benjamin Pariente MD, Nicolas Deaveus MD, and Mustapha Azahaf MD. We are grateful also for valuable input from Jean-Frédéric Colombel MD, Ph.D, and Jean-Yves Mary, Ph.D. Their assistance does not imply endorsement of all the analyses and conclusions of this study, which are of course those of the authors alone.

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Correspondence to David B. Sachar.

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No industrial support was received for the work presented in this article. Dr. Dubinsky serves as a consultant for Janssen, Abbvie, and UCB. Dr. Taouli reports research grant support from Guerbet and Bayer. None of the other authors has a financial interest in any of the products, devices, or drugs mentioned in this manuscript.

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Panchal, H., Wagner, M., Chatterji, M. et al. Earlier Anti-Tumor Necrosis Factor Therapy of Crohn’s Disease Correlates with Slower Progression of Bowel Damage. Dig Dis Sci 64, 3274–3283 (2019). https://doi.org/10.1007/s10620-018-5434-4

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