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Effectiveness of Infliximab on Deep Radiological Remission in Chinese Patients with Perianal Fistulizing Crohn’s Disease

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Abstract

Background and Aims

Information concerning deep radiological healing of perianal fistulas in Chinese patients with CD is limited. The present study aimed to establish the effectiveness of infliximab on CD-related perianal fistulas using magnetic resonance imaging (MRI) and identify predictors of deep radiological remission of fistulas.

Methods

We retrospectively reviewed patients with CD with draining perianal fistulas treated with infliximab and included only those who underwent clinical assessment and MRI before and after infliximab therapy.

Results

Among 178 patients who underwent repeated MRI and clinical assessment, 65.2% had complex fistulas. Post-infliximab therapy, 55.1% of patients with perianal fistulizing CD showed clinical remission and 26.4% presented a clinical response; 38.2% had deep radiological remission, and 34.3% had a partial response based on the Ng score; the Van Assche scores decreased obviously compared with baseline. Prolonged infliximab infusion (18 times) presented higher radiological remission rates in patients with CD with complex fistulas. Concomitant treatment with azathioprine increased the fistula healing rate compared with infliximab alone (50% vs. 36.9%, P < 0.001). Younger age at diagnosis of CD, proctitis and requiring perianal surgery were identified as predictors of poor deep radiological remission of fistulas. Eight of ten patients who stopped infliximab and switched to an alternative agent retained a status of fistula healing in the first year of follow-up.

Conclusions

Infliximab induced deep radiological remission of perianal fistulas in Chinese patients with CD. Routine MRI should be used to monitor fistula healing. Patients with younger age at diagnosis of CD, proctitis, and/or requiring perianal surgery should receive combined therapy and careful monitoring.

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References

  1. Molodecky NA, Soon IS, Rabi DM, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 2012;142:46–54 e42; quiz e30.

  2. Park SH, Kim YJ, Rhee KH, et al. A 30-year trend analysis in the epidemiology of inflammatory bowel disease in the Songpa-Kangdong District of Seoul, Korea in 1986–2015. J Crohns Colitis. 2019;13:1410–1417.

    PubMed  Google Scholar 

  3. Song EM, Lee HS, Kim YJ, et al. Incidence and outcomes of perianal disease in an asian population with Crohn’s disease: a Nationwide Population-Based Study. Dig Dis Sci. 2020;65:1189–1196.

    PubMed  Google Scholar 

  4. Zhao J, Ng SC, Lei Y, et al. First prospective, population-based inflammatory bowel disease incidence study in mainland of China: the emergence of “western” disease. Inflamm Bowel Dis. 2013;19:1839–1845.

    PubMed  Google Scholar 

  5. Zeng Z, Zhu Z, Yang Y, et al. Incidence and clinical characteristics of inflammatory bowel disease in a developed region of Guangdong Province, China: a prospective population-based study. J Gastroenterol Hepatol. 2013;28:1148–1153.

    PubMed  Google Scholar 

  6. Mak WY, Mak OS, Lee CK, et al. Significant medical and surgical morbidity in perianal Crohn’s disease: results from a territory-wide study. J Crohns Colitis. 2018;12:1392–1398.

    PubMed  Google Scholar 

  7. Beaugerie L, Seksik P, Nion-Larmurier I, et al. Predictors of Crohn’s disease. Gastroenterology. 2006;130:650–656.

    PubMed  Google Scholar 

  8. Park SH, Aniwan S, Scott Harmsen W, et al. Update on the natural course of fistulizing perianal Crohn’s disease in a population-based cohort. Inflamm Bowel Dis. 2019;25:1054–1060.

    PubMed  Google Scholar 

  9. Maconi G, Gridavilla D, Vigano C, et al. Perianal disease is associated with psychiatric co-morbidity in Crohn’s disease in remission. Int J Colorectal Dis. 2014;29:1285–1290.

    PubMed  Google Scholar 

  10. Tozer PJ, Burling D, Gupta A, et al. Review article: medical, surgical and radiological management of perianal Crohn’s fistulas. Aliment Pharmacol Ther. 2011;33:5–22.

    CAS  PubMed  Google Scholar 

  11. Kotze PG, Shen B, Lightner AY, et al. Modern management of perianal fistulas in Crohn’s disease: future directions. Gut. 2018;67:1181–1194.

    CAS  PubMed  Google Scholar 

  12. Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med. 2004;350:876–885.

    CAS  PubMed  Google Scholar 

  13. Colombel JF, Sandborn WJ, 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.

    CAS  PubMed  Google Scholar 

  14. Biemans VBC, van der Meulen-de Jong AE, van der Woude CJ, et al. Ustekinumab for Crohn’s disease: results of the ICC Registry, a nationwide prospective observational cohort study. J Crohns Colitis. 2020;14:33–45.

    PubMed  Google Scholar 

  15. Sandborn WJ, Feagan BG, Rutgeerts P, et al. Vedolizumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2013;369:711–721.

    CAS  PubMed  Google Scholar 

  16. Louis E, Mary JY, Vernier-Massouille G, et al. Maintenance of remission among patients with Crohn’s disease on antimetabolite therapy after infliximab therapy is stopped. Gastroenterology 2012;142:63–70 e65; quiz e31.

  17. Domenech E, Hinojosa J, Nos P, et al. Clinical evolution of luminal and perianal Crohn’s disease after inducing remission with infliximab: how long should patients be treated? Aliment Pharmacol Ther. 2005;22:1107–1113.

    CAS  PubMed  Google Scholar 

  18. Gecse KB, Bemelman W, Kamm MA, et al. A global consensus on the classification, diagnosis and multidisciplinary treatment of perianal fistulising Crohn’s disease. Gut. 2014;63:1381–1392.

    PubMed  Google Scholar 

  19. Gecse KB, Sebastian S, Hertogh G, et al. Results of the fifth scientific workshop of the ECCO [II]: clinical aspects of perianal fistulising Crohn’s disease-the unmet needs. J Crohns Colitis. 2016;10:758–765.

    PubMed  Google Scholar 

  20. Gionchetti P, Dignass A, Danese S, et al. 3rd European evidence-based consensus on the diagnosis and management of Crohn’s Disease 2016: part 2: surgical management and special situations. J Crohns Colitis. 2017;11:135–149.

    PubMed  Google Scholar 

  21. Tozer P, Ng SC, Siddiqui MR, et al. Long-term MRI-guided combined anti-TNF-alpha and thiopurine therapy for Crohn’s perianal fistulas. Inflamm Bowel Dis. 2012;18:1825–1834.

    PubMed  Google Scholar 

  22. Chambaz M, Verdalle-Cazes M, Desprez C, et al. Deep remission on magnetic resonance imaging impacts outcomes of perianal fistulizing Crohn’s disease. Dig Liver Dis. 2019;51:358–363.

    PubMed  Google Scholar 

  23. Yan X, Zhu M, Feng Q, et al. Evaluating the effectiveness of infliximab on perianal fistulizing Crohn’s disease by magnetic resonance imaging. Gastroenterol Rep (Oxf). 2019;7:50–56.

    Google Scholar 

  24. Silverberg MS, Satsangi J, Ahmad T, et al. Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol.. 2005;19:5A–36A.

    PubMed  Google Scholar 

  25. Committee American Gastroenterological Association Clinical Practice. American Gastroenterological Association medical position statement: perianal Crohn’s disease. Gastroenterology. 2003;125:1503–1507.

    Google Scholar 

  26. Present DH, Rutgeerts P, Targan S, et al. Infliximab for the treatment of fistulas in patients with Crohn’s disease. N Engl J Med. 1999;340:1398–1405.

    CAS  PubMed  Google Scholar 

  27. Ng SC, Plamondon S, Gupta A, et al. Prospective evaluation of anti-tumor necrosis factor therapy guided by magnetic resonance imaging for Crohn’s perineal fistulas. Am J Gastroenterol. 2009;104:2973–2986.

    CAS  PubMed  Google Scholar 

  28. Van Assche Gert, Vanbeckevoort Dirk, Bielen Didier, et al. Magnetic resonance imaging of the effects of infliximab on perianal fistulizing Crohn’s disease. Am J Gastroenterol. 2003;98:332–339.

    PubMed  Google Scholar 

  29. Ng SC, Plamondon S, Gupta A, et al. Prospective assessment of the effect on quality of life of anti-tumour necrosis factor therapy for perineal Crohn’s fistulas. Aliment Pharmacol Ther. 2009;30:757–766.

    CAS  PubMed  Google Scholar 

  30. Li Y, Chen B, Gao X, et al. Current diagnosis and management of Crohn’s disease in China: results from a multicenter prospective disease registry. BMC Gastroenterol. 2019;19:145.

    PubMed  PubMed Central  Google Scholar 

  31. Bouguen G, Siproudhis L, Gizard E, et al. Long-term outcome of perianal fistulizing Crohn’s disease treated with infliximab. Clin Gastroenterol Hepatol. 2013;11(975–981):e971–e974.

    Google Scholar 

  32. Zeitz J, Fournier N, Labenz C, et al. Risk factors for the development of fistulae and stenoses in Crohn disease patients in the swiss inflammatory bowel disease cohort. Inflamm Intest Dis. 2017;1:172–181.

    PubMed  PubMed Central  Google Scholar 

  33. Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. The Lancet. 2002;359:1541–1549.

    CAS  Google Scholar 

  34. Tougeron D, Savoye G, Savoye-Collet C, et al. Predicting factors of fistula healing and clinical remission after infliximab-based combined therapy for perianal fistulizing Crohn’s disease. Dig Dis Sci. 2009;54:1746–1752.

    CAS  PubMed  Google Scholar 

  35. Castaño-Milla C, Chaparro M, Saro C, et al. Effectiveness of adalimumab in perianal fistulas in crohn’s disease patients naive to anti-TNF therapy. J Clin Gastroenterol. 2015;49:34–40.

    PubMed  Google Scholar 

  36. Schoepfer A, Santos J, Fournier N, et al. Systematic analysis of the impact of diagnostic delay on bowel damage in paediatric versus adult onset Crohn’s disease. J Crohns Colitis. 2019;13:1334–1342.

    PubMed  Google Scholar 

  37. Lionetti P, Bronzini F, Salvestrini C, et al. Response to infliximab is related to disease duration in paediatric Crohn’s disease. Aliment Pharmacol Ther. 2003;18:425–431.

    CAS  PubMed  Google Scholar 

  38. Franke A, McGovern DP, Barrett JC, et al. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn’s disease susceptibility loci. Nat Genet. 2010;42:1118–1125.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Medrano LM, Taxonera C, Gonzalez-Artacho C, et al. Response to infliximab in Crohn’s disease: genetic analysis supporting expression profile. Mediators Inflamm. 2015;2015:318207.

    PubMed  PubMed Central  Google Scholar 

  40. Arijs I, Quintens R, Van Lommel L, et al. Predictive value of epithelial gene expression profiles for response to infliximab in Crohn’s disease. Inflamm Bowel Dis. 2010;16:2090–2098.

    PubMed  Google Scholar 

  41. 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.

    PubMed  Google Scholar 

  42. Lukin DJ. predictors of perianal fistula relapse in Crohn’s disease. Inflamm Bowel Dis. 2019;. https://doi.org/10.1093/ibd/izz198.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Osamura A, Suzuki Y. Fourteen-year anti-TNF therapy in Crohn’s disease patients: clinical characteristics and predictive factors. Dig Dis Sci. 2018;63:204–208.

    CAS  PubMed  Google Scholar 

  44. Yassin NA, Askari A, Warusavitarne J, et al. Systematic review: the combined surgical and medical treatment of fistulising perianal Crohn’s disease. Aliment Pharmacol Ther. 2014;40:741–749.

    CAS  PubMed  Google Scholar 

  45. Colombel JF, Reinisch W, Mantzaris GJ, et al. Randomised clinical trial: deep remission in biologic and immunomodulator naive patients with Crohn’s disease—a SONIC post hoc analysis. Aliment Pharmacol Ther. 2015;41:734–746.

    CAS  PubMed  Google Scholar 

  46. Gomollon F, Dignass A, Annese V, et al. 3rd European evidence-based consensus on the diagnosis and management of Crohn’s disease 2016: Part 1: diagnosis and medical management. J Crohns Colitis. 2017;11:3–25.

    PubMed  Google Scholar 

  47. Jones JL, Kaplan GG, Peyrin-Biroulet L, et al. Effects of concomitant immunomodulator therapy on efficacy and safety of anti-tumor necrosis factor therapy for Crohn’s disease: a meta-analysis of placebo-controlled trials. Clin Gastroenterol Hepatol 2015;13:2233–2240 e2231–2232; quiz e2177–2238.

  48. Qian X, Wang T, Shen J, Ran Z. Low dose of azathioprine is effective to induce and maintain remission in active Crohn disease: a prospective observational study. Medicine (Baltimore). 2018;97:e11814.

    Google Scholar 

  49. Feng T, Chen B, Ungar B, et al. Association of infliximab levels with mucosal healing is time-dependent in Crohn’s disease: higher drug exposure is required postinduction than during maintenance treatment. Inflamm Bowel Dis. 2019;25:1813–1821.

    PubMed  Google Scholar 

  50. El-Matary W, Walters TD, Huynh HQ, et al. Higher postinduction infliximab serum trough levels are associated with healing of fistulizing perianal Crohn’s disease in children. Inflamm Bowel Dis. 2019;25:150–155.

    PubMed  Google Scholar 

  51. Davidov Y, Ungar B, Bar-Yoseph H, et al. Association of induction infliximab levels with clinical response in perianal Crohn’s disease. J Crohns Colitis. 2017;11:549–555.

    PubMed  Google Scholar 

  52. Plevris N, Jenkinson PW, Arnott ID, et al. Higher anti-tumor necrosis factor levels are associated with perianal fistula healing and fistula closure in Crohn’s disease. Eur J Gastroenterol Hepatol. 2020;32:32–37.

    CAS  PubMed  Google Scholar 

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Funding

This work was supported by a grant from the National Natural Science Foundation of China (Nos. 81302095, 81670497, 81701746)

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Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China

    Mingming Zhu, Xitao Xu, Tianrong Wang & Zhihua Ran

  2. Department of Radiology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    Qi Feng & Yunqi Yan

  3. Department of Gastrointestinal Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    Zhe Cui

Authors
  1. Mingming Zhu
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  2. Xitao Xu
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  3. Qi Feng
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  4. Zhe Cui
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  5. Tianrong Wang
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  6. Yunqi Yan
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Contributions

MMZ and XTX designed the research study, prepared the manuscript, and analyzed data. MMZ, XTX, ZC, and TRW contributed to acquisition and interpretation of data. QF analyzed and calculated the MRI data. YQY provided partial MRI data. ZHR contributed to the study design, revising it critically for important intellectual content, and gave final approval of the version to be submitted.

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Correspondence to Zhihua Ran.

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Zhu, M., Xu, X., Feng, Q. et al. Effectiveness of Infliximab on Deep Radiological Remission in Chinese Patients with Perianal Fistulizing Crohn’s Disease. Dig Dis Sci 66, 1658–1668 (2021). https://doi.org/10.1007/s10620-020-06398-w

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