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Digestive Diseases and Sciences

, Volume 62, Issue 2, pp 441–447 | Cite as

Long-Term Outcomes and Predictors of Sustained Response in Patients with Intestinal Behcet’s Disease Treated with Infliximab

  • Jun Zou
  • Da-Nian Ji
  • Jian-fei Cai
  • Jian-long GuanEmail author
  • Zhi-jun BaoEmail author
Original Article

Abstract

Background

Intestinal Behcet’s disease (BD) is a specific subtype of BD. Effective drug therapy for intestinal BD remains elusive.

Aims

To investigate long-term outcomes and identify predictors of sustained response in intestinal BD patients receiving infliximab (IFX) treatment.

Methods

The medical records were reviewed of patients received IFX from September 2012 to March 2016. The cumulative probabilities of sustained response were calculated using the Kaplan–Meier. Predictor factors for sustained response were accessed by receiver operating characteristic curve.

Results

Totally, 27 active intestinal BD patients were enrolled. Sustained responses were observed in 17 patients, after a median follow-up duration 24 months (interquartile range 9–37). The proportion of clinical remission at week 14, 30, and 52 had occurred in 84.6, 70, and 70%, respectively, with the proportion of clinical remission of 69.2, 40, and 55%. The mucosal healing (MH) rate at week 14 was 72%. Kaplan–Meier estimated patients with achievement of clinical and biological responses at week 14 or MH was likely to remain sustained clinical response. ROC curve analysis revealed CRP level (of 6.85 mg/L) at week 14 is a potential predictor for discriminating patients with sustained response from relapse, with an area under the curve values of 0.837.

Conclusions

IFX is effective and safe for induction and maintenance therapy in Chinese patients with moderate-to-severe active intestinal BD. Early achievement of clinical response and mucosal healing might associate long-term response. A lower CRP level seems to be associated with a more benign clinical course.

Keywords

Intestinal Behcet’s disease Infliximab Clinical response Mucosal healing C-reactive protein 

Notes

Compliance with ethical standards

Conflict of interest

Jun Zou, Da-Nian Ji, Jian-fei Cai, Zhi-jun Bao and Jian-long Guan declares that they have no conflict of interest.

Supplementary material

10620_2016_4395_MOESM1_ESM.tif (386 kb)
Supplementary material 1 (TIFF 386 kb)

References

  1. 1.
    Shimizu T, Ehrlich GE, Inaba G, et al. Behcet disease (Behcet syndrome). Semin Arthritis Rheum. 1979;8:223–260.CrossRefPubMedGoogle Scholar
  2. 2.
    Lehner T. Oral ulceration and Behcet’s syndrome. Gut. 1977;18:491–511.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Sakane T, Takeno M, Suzuki N, et al. Behcet’s disease. N Engl J Med. 1999;341:1284–1291.CrossRefPubMedGoogle Scholar
  4. 4.
    Zou J, Shen Y, Ji DN, et al. Endoscopic findings of gastrointestinal involvement in Chinese patients with Behcet’s disease. World J Gastroenterol.. 2014;20:17171–17178.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Lakhanpal S, Tani K, Lie JT, et al. Pathologic features of Behcet’s syndrome: a review of Japanese autopsy registry data. Hum Pathol. 1985;16:790–795.CrossRefPubMedGoogle Scholar
  6. 6.
    Kasahara Y, Tanaka S, Nishino M, et al. Intestinal involvement in Behcet’s disease: review of 136 surgical cases in the Japanese literature. Dis Colon Rectum. 1981;24:103–106.CrossRefPubMedGoogle Scholar
  7. 7.
    Ketch LL, Buerk CA, Liechty D. Surgical implications of Behcet’s disease. Arch Surg. 1980;115:759–760.CrossRefPubMedGoogle Scholar
  8. 8.
    Naganuma M, Iwao Y, Inoue N, et al. Analysis of clinical course and long-term prognosis of surgical and nonsurgical patients with intestinal Behcet’s disease. Am J Gastroenterol. 2000;95:2848–2851.PubMedGoogle Scholar
  9. 9.
    Travis SP, Czajkowski M, McGovern DP, Watson RG, Bell AL. Treatment of intestinal Behcet’s syndrome with chimeric tumour necrosis factor alpha antibody. Gut. 2001;49:725–728.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Arida A, Fragiadaki K, Giavri E, et al. Anti-TNF agents for Behcet’s disease: analysis of published data on 369 patients. Semin Arthritis Rheum. 2011;41:61–70.CrossRefPubMedGoogle Scholar
  11. 11.
    Kinoshita H, Kunisaki R, Yamamoto H, et al. Efficacy of infliximab in patients with intestinal Behcet’s disease refractory to conventional medication. Intern Med. 2013;52:1855–1862.CrossRefPubMedGoogle Scholar
  12. 12.
    Lee JH, Cheon JH, Jeon SW, et al. Efficacy of infliximab in intestinal Behcet’s disease: a Korean multicenter retrospective study. Inflamm Bowel Dis. 2013;19:1833–1838.PubMedGoogle Scholar
  13. 13.
    Mizushima Y. Recent research into Behcet’s disease in Japan. Int J Tissue React. 1988;10:59–65.PubMedGoogle Scholar
  14. 14.
    Cheon JH, Han DS, Park JY, et al. Development, validation, and responsiveness of a novel disease activity index for intestinal Behcet’s disease. Inflamm Bowel Dis. 2011;17:605–613.CrossRefPubMedGoogle Scholar
  15. 15.
    Lichtenstein GR, Feagan BG, Cohen RD, et al. Serious infections and mortality in association with therapies for Crohn’s disease: TREAT registry. Clin Gastroenterol Hepatol. 2006;4:621–630.CrossRefPubMedGoogle Scholar
  16. 16.
    Vallet H, Riviere S, Sanna A, et al. Efficacy of anti-TNF alpha in severe and/or refractory Behcet’s disease: multicenter study of 124 patients. J Autoimmun. 2015;62:67–74.CrossRefPubMedGoogle Scholar
  17. 17.
    Hisamatsu T, Ueno F, Matsumoto T, et al. The 2nd edition of consensus statements for the diagnosis and management of intestinal Behcet’s disease: indication of anti-TNFalpha monoclonal antibodies. J Gastroenterol. 2014;49:156–162.CrossRefPubMedGoogle Scholar
  18. 18.
    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. quiz e10-1.CrossRefPubMedGoogle Scholar
  19. 19.
    De Cruz P, Kamm MA, Prideaux L, et al. Mucosal healing in Crohn’s disease: a systematic review. Inflamm Bowel Dis. 2013;19:429–444.CrossRefPubMedGoogle Scholar
  20. 20.
    Rutgeerts P, Geboes K, Vantrappen G, et al. Natural history of recurrent Crohn’s disease at the ileocolonic anastomosis after curative surgery. Gut. 1984;25:665–672.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Rutgeerts P, Geboes K, Vantrappen G, et al. Predictability of the postoperative course of Crohn’s disease. Gastroenterology. 1990;99:956–963.CrossRefPubMedGoogle Scholar
  22. 22.
    D’Haens G, Geboes K, Rutgeerts P. Endoscopic and histologic healing of Crohn’s (ileo-) colitis with azathioprine. Gastrointest Endosc. 1999;50:667–671.CrossRefPubMedGoogle Scholar
  23. 23.
    Hanauer SB, Feagan BG, Lichtenstein GR, et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet. 2002;359:1541–1549.CrossRefPubMedGoogle Scholar
  24. 24.
    Pepys MB, Hirschfield GM. C-reactive protein: a critical update. J Clin Invest. 2003;111:1805–1812.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Emery P, Gabay C, Kraan M, et al. Evidence-based review of biologic markers as indicators of disease progression and remission in rheumatoid arthritis. Rheumatol Int. 2007;27:793–806.CrossRefPubMedGoogle Scholar
  26. 26.
    Johnson HL, Chiou CC, Cho CT. Applications of acute phase reactants in infectious diseases. J Microbiol Immunol Infect. 1999;32:73–82.PubMedGoogle Scholar
  27. 27.
    Reinisch W, Wang Y, Oddens BJ, et al. C-reactive protein, an indicator for maintained response or remission to infliximab in patients with Crohn’s disease: a post hoc analysis from ACCENT I. Aliment Pharmacol Ther. 2012;35:568–576.CrossRefPubMedGoogle Scholar
  28. 28.
    Kiss LS, Szamosi T, Molnar T, et al. Early clinical remission and normalisation of CRP are the strongest predictors of efficacy, mucosal healing and dose escalation during the first year of adalimumab therapy in Crohn’s disease. Aliment Pharmacol Ther. 2011;34:911–922.CrossRefPubMedGoogle Scholar
  29. 29.
    Lee LY, Sanderson JD, Irving PM. Anti-infliximab antibodies in inflammatory bowel disease: prevalence, infusion reactions, immunosuppression and response, a meta-analysis. Eur J Gastroenterol Hepatol. 2012;24:1078–1085.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of Immunology and Rheumatology, Huadong HospitalFudan UniversityShanghaiChina
  2. 2.Center of Gastrointestinal Endoscopy, Huadong HospitalFudan UniversityShanghaiChina
  3. 3.Department of Gastroenterology, Huadong HospitalFudan UniversityShanghaiChina
  4. 4.Shanghai Key Laboratory of Clinical Geriatric Medicine, Research Center on Aging and MedicineFudan UniversityShanghaiChina

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