Digestive Diseases and Sciences

, Volume 58, Issue 12, pp 3592–3599 | Cite as

Severe Disease Activity and Cytomegalovirus Colitis Are Predictive of a Nonresponse to Infliximab in Patients with Ulcerative Colitis

  • Sang Hyoung Park
  • Suk-Kyun Yang
  • Seung-Mo Hong
  • Soo-Kyung Park
  • Jong Wook Kim
  • Hyo Jeong Lee
  • Dong-Hoon Yang
  • Kee Wook Jung
  • Kyung-Jo Kim
  • Byong Duk Ye
  • Jeong-Sik Byeon
  • Seung-Jae Myung
  • Jin-Ho Kim
Original Article

Abstract

Background and Aims

The role of infliximab in the treatment of patients with ulcerative colitis (UC) in Asia is still unclear. The aim of this study was to evaluate the clinical outcomes of infliximab therapy in Korean UC patients, including efficacy and predictors of response.

Methods

Patients who received infliximab induction therapy for moderate to severe UC at Asan Medical Center were retrospectively analyzed. The demographic characteristics of these patients and their clinical outcomes following infliximab therapy were evaluated.

Results

Of the 89 UC patients receiving infliximab induction therapy, 53 (59.6 %) were steroid-refractory and 36 (40.4 %) were steroid-dependent. At the initiation of infliximab, the median Mayo score was 9 (range 7–12). After the induction therapy of infliximab, 59 patients (66.3 %) demonstrated a clinical response at week 8, of which 29 (32.6 %) were determined to be in clinical remission. A colectomy was performed within 1 year after infliximab initiation in 11 (36.7 %) of 30 patients who displayed no clinical response to infliximab therapy, but in none of the 59 patients who showed a response to this drug (p < 0.001). Multivariate regression analysis identified severe disease (Mayo score ≥ 11) at the initiation of infliximab (p = 0.007) and history of cytomegalovirus colitis within 3 months prior to infliximab treatment (p = 0.001) as independent positive predictors of nonresponse to infliximab.

Conclusions

The efficacy of infliximab in Korean UC patients seems to be similar to that of previously published Western reports. Severe disease and a history of cytomegalovirus colitis are predictors of a nonresponse to infliximab.

Keywords

Ulcerative colitis Infliximab Response Cytomegalovirus 

Notes

Acknowledgments

This study was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (A120176). Suk-Kyun Yang has received a research grant from Janssen Korea Ltd.

Conflict of interest

None.

References

  1. 1.
    Podolsky DK. Inflammatory bowel disease. N Engl J Med. 2002;347:417–429.PubMedCrossRefGoogle Scholar
  2. 2.
    Langholz E, Munkholm P, Davidsen M, Binder V. Colorectal cancer risk and mortality in patients with ulcerative colitis. Gastroenterology. 1992;103:1444–1451.PubMedGoogle Scholar
  3. 3.
    Shibolet O, Regushevskaya E, Brezis M, Soares-Weiser K. Cyclosporine A for induction of remission in severe ulcerative colitis. Cochrane Database Syst Rev 2005; 1:CD004277.Google Scholar
  4. 4.
    Knight DM, Trinh H, Le J, et al. Construction and initial characterization of a mouse-human chimeric anti-TNF antibody. Mol Immunol. 1993;30:1443–1453.PubMedCrossRefGoogle Scholar
  5. 5.
    Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353:2462–2476.PubMedCrossRefGoogle Scholar
  6. 6.
    Jarnerot G, Hertervig E, Friis-Liby I, et al. Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study. Gastroenterology. 2005;128:1805–1811.PubMedCrossRefGoogle Scholar
  7. 7.
    Su C, Salzberg BA, Lewis JD, et al. Efficacy of anti-tumor necrosis factor therapy in patients with ulcerative colitis. Am J Gastroenterol. 2002;97:2577–2584.PubMedCrossRefGoogle Scholar
  8. 8.
    Ferrante M, Vermeire S, Katsanos KH, et al. Predictors of early response to infliximab in patients with ulcerative colitis. Inflamm Bowel Dis. 2007;13:123–128.PubMedCrossRefGoogle Scholar
  9. 9.
    Jurgens M, Laubender RP, Hartl F, et al. Disease activity, ANCA, and IL23R genotype status determine early response to infliximab in patients with ulcerative colitis. Am J Gastroenterol. 2010;105:1811–1819.PubMedCrossRefGoogle Scholar
  10. 10.
    Ferrante M, Vermeire S, Fidder H, et al. Long-term outcome after infliximab for refractory ulcerative colitis. J Crohns Colitis. 2008;2:219–225.PubMedCrossRefGoogle Scholar
  11. 11.
    Lees CW, Heys D, Ho GT, et al. A retrospective analysis of the efficacy and safety of infliximab as rescue therapy in acute severe ulcerative colitis. Aliment Pharmacol Ther. 2007;26:411–419.PubMedCrossRefGoogle Scholar
  12. 12.
    Seow CH, Newman A, Irwin SP, Steinhart AH, Silverberg MS, Greenberg GR. Trough serum infliximab: a predictive factor of clinical outcome for infliximab treatment in acute ulcerative colitis. Gut. 2010;59:49–54.PubMedCrossRefGoogle Scholar
  13. 13.
    Hou JK, El-Serag H, Thirumurthi S. Distribution and manifestations of inflammatory bowel disease in Asians, Hispanics, and African Americans: a systematic review. Am J Gastroenterol. 2009;104:2100–2109.PubMedCrossRefGoogle Scholar
  14. 14.
    Thia KT, Loftus EV Jr, Sandborn WJ, Yang SK. An update on the epidemiology of inflammatory bowel disease in Asia. Am J Gastroenterol. 2008;103:3167–3182.PubMedCrossRefGoogle Scholar
  15. 15.
    Yang SK, Yun S, Kim JH, et al. Epidemiology of inflammatory bowel disease in the Songpa-Kangdong district, Seoul, Korea, 1986-2005: a KASID study. Inflamm Bowel Dis. 2008;14:542–549.PubMedCrossRefGoogle Scholar
  16. 16.
    Garland CF, Lilienfeld AM, Mendeloff AI, Markowitz JA, Terrell KB, Garland FC. Incidence rates of ulcerative colitis and Crohn’s disease in fifteen areas of the United States. Gastroenterology. 1981;81:1115–1124.PubMedGoogle Scholar
  17. 17.
    Binder V, Both H, Hansen PK, Hendriksen C, Kreiner S, Torp-Pedersen K. Incidence and prevalence of ulcerative colitis and Crohn’s disease in the County of Copenhagen, 1962 to 1978. Gastroenterology. 1982;83:563–568.PubMedGoogle Scholar
  18. 18.
    Tysk C, Jarnerot G. Ulcerative proctocolitis in Orebro, Sweden. A retrospective epidemiologic study, 1963-1987. Scand J Gastroenterol. 1992;27:945–950.PubMedCrossRefGoogle Scholar
  19. 19.
    Yang SK, Hong WS, Min YI, et al. Incidence and prevalence of ulcerative colitis in the Songpa-Kangdong District, Seoul, Korea, 1986-1997. J Gastroenterol Hepatol. 2000;15:1037–1042.PubMedCrossRefGoogle Scholar
  20. 20.
    Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med. 1987;317:1625–1629.PubMedCrossRefGoogle Scholar
  21. 21.
    Dignass A, Eliakim R, Magro F, et al. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis Part 1: Definitions and diagnosis. J Crohns Colitis. 2012;6:965–990.PubMedCrossRefGoogle Scholar
  22. 22.
    Rahier JF, Ben-Horin S, Chowers Y, et al. European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease. J Crohns Colitis. 2009;3:47–91.PubMedCrossRefGoogle 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.PubMedCrossRefGoogle Scholar
  24. 24.
    Sands BE, Anderson FH, Bernstein CN, et al. Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med. 2004;350:876–885.PubMedCrossRefGoogle Scholar
  25. 25.
    Fuss IJ, Neurath M, Boirivant M, et al. Disparate CD4 + lamina propria (LP) lymphokine secretion profiles in inflammatory bowel disease. Crohn’s disease LP cells manifest increased secretion of IFN-gamma, whereas ulcerative colitis LP cells manifest increased secretion of IL-5. J Immunol. 1996;157:1261–1270.PubMedGoogle Scholar
  26. 26.
    Yang SK, Jung Y, Hong M, et al. No association between TNFSF15 and IL23R with ulcerative colitis in Koreans. J Hum Genet. 2011;56:200–204.PubMedCrossRefGoogle Scholar
  27. 27.
    Park SH, Kim YM, Yang SK, et al. Clinical features and natural history of ulcerative colitis in Korea. Inflamm Bowel Dis. 2007;13:278–283.PubMedCrossRefGoogle Scholar
  28. 28.
    Solberg IC, Lygren I, Jahnsen J, et al. Clinical course during the first 10 years of ulcerative colitis: results from a population-based inception cohort (IBSEN Study). Scand J Gastroenterol. 2009;44:431–440.PubMedCrossRefGoogle Scholar
  29. 29.
    Langholz E, Munkholm P, Davidsen M, Binder V. Course of ulcerative colitis: analysis of changes in disease activity over years. Gastroenterology. 1994;107:3–11.PubMedGoogle Scholar
  30. 30.
    Farmer RG, Easley KA, Rankin GB. Clinical patterns, natural history, and progression of ulcerative colitis. A long-term follow-up of 1116 patients. Dig Dis Sci. 1993;38:1137–1146.PubMedCrossRefGoogle Scholar
  31. 31.
    Oussalah A, Evesque L, Laharie D, et al. A multicenter experience with infliximab for ulcerative colitis: outcomes and predictors of response, optimization, colectomy, and hospitalization. Am J Gastroenterol. 2010;105:2617–2625.PubMedCrossRefGoogle Scholar
  32. 32.
    Truelove SC, Witts LJ. Cortisone in ulcerative colitis; final report on a therapeutic trial. Br Med J. 1955;2:1041–1048.PubMedCrossRefGoogle Scholar
  33. 33.
    Lawlor G, Moss AC. Cytomegalovirus in inflammatory bowel disease: pathogen or innocent bystander? Inflamm Bowel Dis. 2010;16:1620–1627.PubMedCrossRefGoogle Scholar
  34. 34.
    Cannon MJ, Schmid DS, Hyde TB. Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection. Rev Med Virol. 2010;20:202–213.PubMedCrossRefGoogle Scholar
  35. 35.
    Kim YS, Kim YH, Kim JS, et al. The prevalence and efficacy of ganciclovir on steroid-refractory ulcerative colitis with cytomegalovirus infection: a prospective multicenter study. J Clin Gastroenterol. 2012;46:51–56.PubMedCrossRefGoogle Scholar
  36. 36.
    Roblin X, Pillet S, Oussalah A, et al. Cytomegalovirus load in inflamed intestinal tissue is predictive of resistance to immunosuppressive therapy in ulcerative colitis. Am J Gastroenterol. 2011;106:2001–2008.PubMedCrossRefGoogle Scholar
  37. 37.
    Matsuoka K, Iwao Y, Mori T, et al. Cytomegalovirus is frequently reactivated and disappears without antiviral agents in ulcerative colitis patients. Am J Gastroenterol. 2007;102:331–337.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Sang Hyoung Park
    • 1
  • Suk-Kyun Yang
    • 1
  • Seung-Mo Hong
    • 2
  • Soo-Kyung Park
    • 1
  • Jong Wook Kim
    • 1
    • 3
  • Hyo Jeong Lee
    • 1
  • Dong-Hoon Yang
    • 1
  • Kee Wook Jung
    • 1
  • Kyung-Jo Kim
    • 1
  • Byong Duk Ye
    • 1
  • Jeong-Sik Byeon
    • 1
  • Seung-Jae Myung
    • 1
  • Jin-Ho Kim
    • 1
  1. 1.Department of Gastroenterology, Asan Medical CenterUniversity of Ulsan College of MedicineSongpa-gu, SeoulKorea
  2. 2.Department of Pathology, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulKorea
  3. 3.Division of Gastroenterology, Department of Internal MedicineInje University Ilsan Paik HospitalGoyang-siKorea

Personalised recommendations