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Clinical Impact of Sonographic Transmural Healing After Anti-TNF Antibody Treatment in Patients with Crohn’s Disease

  • José María ParedesEmail author
  • Nadia Moreno
  • Patricia Latorre
  • Tomás Ripollés
  • María Jesús Martinez
  • José Vizuete
  • Eduardo Moreno-Osset
Original Article
  • 22 Downloads

Abstract

Aim

To assess the clinical benefits of transmural healing (TH) shown on intestinal ultrasound (IUS) after treatment with tumor necrosis factor-alpha antibodies (anti-TNF) in patients with Crohn’s disease.

Materials and Methods

This prospective study included consecutively 36 patients who underwent IUS in the week prior to start anti-TNF treatment, at 12 weeks, and 1 year after starting treatment. The clinical response to treatment was assessed using the Crohn’s disease activity index and C-reactive protein (CRP) values. TH was defined as the normalization of bowel wall thickness on IUS. Treated patients were considered to have a good outcome if none of the following situations presented: need to reintroduce corticosteroids or intensify maintenance therapy and/or need for surgery.

Results

After the induction regimen, 29 patients (80.6%) achieved clinical remission, and serum CRP values returned to normal in 20 patients (55.6%). In the IUS at 12 weeks, treatment induced a statistically significant reduction in the wall thickness (p < 0.001) and color Doppler grade (p < 0.001), as well as resolution of complications in 66.7% of patients (p < 0.03). IUS after 1 year of biological therapy showed TH in 14/33 patients (42.4%). During the follow-up (median 48.5 months), 23 of the 33 (69.7%) patients in remission or response after induction therapy presented a good outcome. Sonographic TH was significantly related with better outcomes, with only 1/14 patients having a poor outcome compared to 9/19 without TH (OR 11.7, 95% CI 1.2–108.2 p = 0.01, Chi-squared test).

Conclusion

Patients who achieve TH on IUS with biological treatment have better clinical outcomes.

Keywords

Crohn’s disease Abdominal ultrasound Transmural healing Biological therapy 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statement

The approval of our center’s Ethics Committee was obtained in order to conduct of the study (ECRAYM 2008). Prior to their inclusion in the study, patients were informed of its nature and gave their written consent.

References

  1. 1.
    Rutgeerts P, Vermeire S, Van Assche G. Biological therapies for inflammatory bowel diseases. Gastroenterology. 2009;135:1182–1197.CrossRefGoogle Scholar
  2. 2.
    Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet. 2002;359:1541–1549.CrossRefGoogle Scholar
  3. 3.
    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.CrossRefGoogle Scholar
  4. 4.
    Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med. 2004;350:876–885.CrossRefGoogle Scholar
  5. 5.
    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
  6. 6.
    Feagan BG, Vreeland MG, Larson LR, Bala MV. Annual cost of care for Crohn’s disease: a payor perspective. Am J Gastroenterol. 2000;95:1955–1960.CrossRefGoogle Scholar
  7. 7.
    Colombel J-F, 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.CrossRefGoogle Scholar
  8. 8.
    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.CrossRefGoogle Scholar
  9. 9.
    Rutgeerts P, Diamond RH, 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;63:433–442.CrossRefGoogle Scholar
  10. 10.
    Baert F, Moortgat L, Van Assche G, et al. Mucosal healing predicts sustained clinical remission in patients with early-stage Crohn’s disease. Gastroenterology. 2010;138:463–468.CrossRefGoogle Scholar
  11. 11.
    Frøslie KF, Jahnsen J, Moum BA, Vatn MH, IBSEN Group. Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort. Gastroenterology. 2007;133:412–422.CrossRefGoogle Scholar
  12. 12.
    Gisbert JP, Panés J. Loss of response and requirement of infliximab dose intensification in Crohn’s disease: a review. Am J Gastroenterol. 2009;104:760–767.CrossRefGoogle Scholar
  13. 13.
    Burri E, Beglinger C, Lehmann FS. Monitoring of therapy for inflammatory bowel disease. Digestion. 2012;86:1–5.CrossRefGoogle Scholar
  14. 14.
    Neurath MF, Travis SP. Mucosal healing in inflammatory bowel diseases: a systematic review. Gut. 2012;61:1619–1635.CrossRefGoogle Scholar
  15. 15.
    Navaneethan U, Parasa S, Venkatesh PG, Trikudanathan G, Shen B. Prevalence and risk factors for colonic perforation during colonoscopy in hospitalized inflammatory bowel disease patients. J Crohns Colitis. 2011;5:189–195.CrossRefGoogle Scholar
  16. 16.
    Navaneethan U, Kochhar G, Phull H, et al. Severe disease on endoscopy and steroid use increase the risk for bowel perforation during colonoscopy in inflammatory bowel disease patients. J Crohns Colitis. 2012;6:470–475.CrossRefGoogle Scholar
  17. 17.
    Panés J, Bouzas R, Chaparro M, et al. Systematic review: the use of ultrasonography, computed tomography and magnetic resonance imaging for the diagnosis, assessment of activity and abdominal complications of Crohn’s disease. Aliment Pharmacol Ther. 2011;34:125–145.CrossRefGoogle Scholar
  18. 18.
    Horsthuis K, Bipat S, Bennink RJ, Stoker J. Inflammatory bowel disease diagnosed with US, MR, scintigraphy, and CT: metaanalysis of prospective studies. Radiology. 2008;247:64–79.CrossRefGoogle Scholar
  19. 19.
    Fraquelli M, Colli A, Casazza G, et al. Role of US in detection of Crohn disease: meta-analysis. Radiology. 2005;236:95–101.CrossRefGoogle Scholar
  20. 20.
    Paredes JM, Ripollés T, Cortés X, et al. Abdominal sonographic changes after antibody to tumor necrosis factor (anti-TNF) alpha therapy in Crohn’s Disease. Dig Dis Sci. 2010;55:404–410.  https://doi.org/10.1007/s10620-009-0759-7.CrossRefGoogle Scholar
  21. 21.
    Thomson M, Rao P, Berger L, Rawat D. Graded compression and power Doppler ultrasonography versus endoscopy to assess paediatric Crohn disease activity pre- and posttreatment. J Pediatr Gastroenterol Nutr. 2012;54:404–408.CrossRefGoogle Scholar
  22. 22.
    Quaia E, Migaleddu V, Baratella E, et al. The diagnostic value of small bowel wall vascularity after sulphur hexafluoride-filled microbubble injection in patients with Crohn’s disease. Correlation with the therapeutic effectiveness of specific anti-inflammatory treatment. Eur J Radiol. 2009;69:438–444.CrossRefGoogle Scholar
  23. 23.
    Castiglione F, Testa A, Rea M, et al. Transmural healing evaluated by bowel sonography in patients with Crohn’s disease on maintenance treatment with biologics. Inflamm Bowel Dis. 2013;19:1928–1934.CrossRefGoogle Scholar
  24. 24.
    Moreno N, Ripollés T, Paredes JM, et al. Usefulness of abdominal ultrasonography in the analysis of endoscopic activity in patients with Crohn’s disease: changes following treatment with immunomodulators and/or anti-TNF antibodies. J Crohns Colitis. 2014;8:1079–1087.CrossRefGoogle Scholar
  25. 25.
    Lennard-Jones JE. Classification of inflammatory bowel disease. Scand J Gastroenterol Suppl. 1989;170:2–6.CrossRefGoogle Scholar
  26. 26.
    Dignass A, Van Assche G, Lindsay JO, et al. The second European evidence-based Consensus on the diagnosis and management of Crohn’s disease: current management. J Crohns Colitis. 2010;4:28–62.CrossRefGoogle Scholar
  27. 27.
    Nylund K, Maconi G, Hollerweger A, et al. EFSUMB recommendations and guidelines for gastrointestinal ultrasound. Ultraschall Med. 2017;38:273–284.CrossRefGoogle Scholar
  28. 28.
    Patriquin HB, Garcier JM, Lafortune M, et al. Appendicitis in children and young adults: Doppler sonographic-pathologic correlation. AJR Am J Roentgenol. 1996;166:629–633.CrossRefGoogle Scholar
  29. 29.
    Bouguen G, Levesque BG, Feagan BG, et al. Treat to target: a proposed new paradigm for the management of Crohn’s disease. Clin Gastroenterol Hepatol. 2015;13:1042–1050.CrossRefGoogle Scholar
  30. 30.
    Sauer CG, Middleton JP, McCracken C, et al. Magnetic resonance enterography (MRE) healing and MRE remission predicts improved outcome in pediatric Crohn disease. J Pediatr Gastroenterol Nutr. 2016;62:378–383.CrossRefGoogle Scholar
  31. 31.
    Deepak P, Fletcher JG, Fidler JL, et al. radiological response is associated with better long-term outcomes and is a potential treatment target in patients with small bowel Crohn’s disease. Am J Gastroenterol. 2016;111:997–1006.CrossRefGoogle Scholar
  32. 32.
    Fernandes SR, Rodrigues RV, Bernardo S, et al. Transmural healing is associated with improved long-term outcomes of patients with Crohn’s disease. Inflamm Bowel Dis. 2017;23:1403–1409.CrossRefGoogle Scholar
  33. 33.
    Lopes S, Andrade P, Cunha R, Magro F. Transmural healing in Crohn’s disease: beyond mural findings. Dig Liver Dis. 2018;50:103–104.CrossRefGoogle Scholar
  34. 34.
    Castiglione F, Mainenti P, Testa A, et al. Cross-sectional evaluation of transmural healing in patients with Crohn’s disease on maintenance treatment with anti-TNF alpha agents. Dig Liver Dis. 2017;49:484–489.CrossRefGoogle Scholar
  35. 35.
    Yuksel I, Kilincalp S. Cross-sectional evaluation of transmural healing in Crohn’s disease: mural and mesenteric parameters. Dig Liver Dis. 2018;50:105.CrossRefGoogle Scholar
  36. 36.
    Castiglione F, Testa A, Imperatore N, Rispo A. Transmural healing in Crohn’s disease: beyond mural findings—Authors’ reply. Dig Liver Dis. 2018;50:104–105.CrossRefGoogle Scholar
  37. 37.
    Castiglione F, Testa A, Imperatore N, Rispo A. Cross-sectional evaluation of transmural healing in Crohn’s disease: mural and mesenteric parameters—Authors’ reply. Dig Liver Dis. 2018;50:211–212.CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  1. 1.Department of Digestive Medicine, Hospital Universitario Dr. PesetUniversity of ValenciaValenciaSpain
  2. 2.Department of Diagnostic Radiology, Hospital Universitario Dr. PesetValenciaSpain

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