Clinical and Biological Prognostic Markers in Crohn’s Disease
suffered a relapse were higher than in non-relapsing patients (p<0.001) and relapse risk was higher in patients with high FC concentrations and a positive FL.75
Summary and Conclusion
CD represents a heterogeneous entity and the rate at which a patient progresses to complicated disease varies significantly. Accordingly, the ability to predict which patients are likely to develop complicated disease at the time of diagnosis is essential for informing patients about their potential prognosis, closer follow-up of patients at risk, and, importantly, trying to modify disease course with more robust treatment strategies. This has become particularly important over the past decade with the increasing use of biological and immunomodulator therapies.
Although the early use of these therapies might modify disease course, decrease hospitalizations, prevent surgeries, and decrease the need for steroid treatment,12–14
they may be associated with significant side effects and are expensive. Importantly, they may not be needed for the
1. Baumgart DC, Sandborn WJ, Inflammatory bowel disease: clinical aspects and established and evolving therapies, Lancet, 2007;369:1641–57.
2. Xavier RJ, Podolsky DK, Unravelling the pathogenesis of inflammatory bowel disease, Nature, 2007;448:427–34.
3. Strober W, Fuss I, Mannon P, The fundamental basis of inflammatory bowel disease, J Clin Invest, 2007;117:514–21.
4. Munkholm P, Langholz E, Davidsen M, et al., Disease activity courses in a regional cohort of Crohn’s disease patients, Scand J Gastroenterol, 1995;30:699–706.
5. Louis E, Collard A, Oger AF, et al., Behaviour of Crohn’s disease according to the Vienna classification: changing pattern over the course of the disease, Gut, 2001;49:777–82.
6. Lichtenstein GR, Hanauer SB, Sandborn WJ, Management of Crohn’s disease in adults, Am J Gastroenterol, 2009;104:465–83.
7. Sandborn WJ, Feagan BG, Review article: mild to moderate Crohn’s disease—defining the basis for a new treatment algorithm, Aliment Pharmacol Ther, 2003;18:263–77.
8. Benchimol EI, Seow CH, Steinhart AH, et al., Traditional corticosteroids for induction of remission in Crohn’s disease, Cochrane Database Syst Rev, 2008;CD006792.
9. Seow CH, Benchimol EI, Griffiths AM, et al., Budesonide for induction of remission in Crohn’s disease, Cochrane Database Syst Rev, 2008;CD000296.
10. Schwartz M, Cohen R, Optimizing conventional therapy for inflammatory bowel disease, Curr Gastroenterol Rep, 2008;10:585–90.
11. Shergill AK, Terdiman JP, Controversies in the treatment of Crohn’s disease: the case for an accelerated step-up treatment approach, World J Gastroenterol, 2008;14:2670–7.
12. 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;63:433–42.
13. D’Haens G, Baert F, van Assche G, et al., Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn’s disease: an open randomised trial, Lancet, 2008;371:660–7.
14. D’Haens GR, Top-down therapy for IBD: rationale and requisite evidence, Nat Rev Gastroenterol Hepatol, 2010;7:86–92.
15. Vermeire S, van Assche G, Rutgeerts P, Review article: Altering the natural history of Crohn’s disease—evidence for and against current therapies, Aliment Pharmacol Ther, 2007;25:3–12.
16. Dotan I, Disease behavior in adult patients: are there predictors for stricture or fistula formation?, Dig Dis, 2009;27:206–11.
17. Romberg-Camps MJ, Dagnelie PC, Kester AD, et al., Influence of phenotype at diagnosis and of other potential prognostic factors on the course of inflammatory bowel disease, Am J Gastroenterol, 2009;104:371–83.
18. Louis E, Michel V, Hugot JP, et al., Early development of stricturing or penetrating pattern in Crohn’s disease is influenced by disease location, number of flares, and smoking but not by NOD2/CARD15 genotype, Gut, 2003;52:552–7.
19. Lakatos PL, Czegledi Z, Szamosi T, et al., Perianal disease, small bowel disease, smoking, prior steroid or early azathioprine/ biological therapy are predictors of disease behavior change in patients with Crohn’s disease, World J Gastroenterol, 2009;15:3504–10.
20. Veloso FT, Ferreira JT, Barros L, et al., Clinical outcome of
subgroup of patients destined to have a benign disease course, thus justifying optimal treatment-to-patient adjustment.
Adopting risk-stratification approaches to CD treatment is therefore desirable and studies have identified a number of clinical, serologic, and genetic markers that are associated with complicated disease behavior in CD. A tailored treatment approach could potentially employ logical panels of these markers to aid patient selection and individualized care. However, the prognostic utility of the majority of these markers in clinical practice has not yet been prospectively assessed. Further large, prospective clinical trials are therefore needed to determine the practical clinical value of these assessments in CD and how best to utilize these assays in a cost-effective manner. Nevertheless, most current data are promising and suggest that genetic, serological, and fecal markers can identify those patients most likely to benefit from the early use of more intensive biological and immunomodulator therapies. These factors are therefore expected to play an important role in future diagnostic and treatment algorithms in CD. n
Crohn’s disease: analysis according to the Vienna classification and clinical activity, Inflamm Bowel Dis, 2001;7:306–13.
21. Beaugerie L, Seksik P, Nion-Larmurier I, et al., Predictors of Crohn’s disease, Gastroenterology, 2006;130:650–6.
22. Loly C, Belaiche J, Louis E, Predictors of severe Crohn’s disease, Scand J Gastroenterol, 2008;43:948–54.
23. Solberg IC, Vatn MH, Hoie O, et al., Clinical course in Crohn’s disease: results of a Norwegian population-based ten-year follow-up study, Clin Gastroenterol Hepatol, 2007;5:1430–8.
24. Van Limbergen J, Russell RK, Drummond HE, et al., Definition of phenotypic characteristics of childhood-onset inflammatory bowel disease, Gastroenterology, 2008;135:1114–22.
25. Cosnes J, Carbonnel F, Beaugerie L, et al., Effects of cigarette smoking on the long-term course of Crohn’s disease, Gastroenterology, 1996;110:424–31.
26. Brant SR, Picco MF, Achkar JP, et al., Defining complex contributions of NOD2/CARD15 gene mutations, age at onset, and tobacco use on Crohn’s disease phenotypes, Inflamm Bowel Dis, 2003;9:281–9.
27. Seksik P, Nion-Larmurier I, Sokol H, et al., Effects of light smoking consumption on the clinical course of Crohn’s disease, Inflamm Bowel Dis, 2009;15:734–41.
28. Lichtenstein GR, Emerging prognostic markers to determine Crohn’s disease natural history and improve management strategies: a review of recent literature, Gastroenterol Hepatol (N Y), 2010;6:99–107.
29. Allez M, Lemann M, Role of endoscopy in predicting the disease course in inflammatory bowel disease, World J Gastroenterol, 16:2626–32.
30. Allez M, Lemann M, Bonnet J, et al., Long term outcome of patients with active Crohn’s disease exhibiting extensive and deep ulcerations at colonoscopy, Am J Gastroenterol, 2002;97:947–53.
31. Volanakis JE, Human C-reactive protein: expression, structure, and function, Mol Immunol, 2001;38:189–97.
32. Fagan EA, Dyck RF, Maton PN, et al., Serum levels of C-reactive protein in Crohn’s disease and ulcerative colitis, Eur J Clin Invest, 1982;12:351–9.
33. Karoui S, Ouerdiane S, Serghini M, et al., Correlation between levels of C-reactive protein and clinical activity in Crohn’s disease, Dig Liver Dis, 2007;39:1006–10.
34. Jones J, Loftus EV Jr., Panaccione R, et al., Relationships between disease activity and serum and fecal biomarkers in patients with Crohn’s disease, Clin Gastroenterol Hepatol, 2008;6:1218–24.
35. Koelewijn CL, Schwartz MP, Samsom M, et al., C-reactive protein levels during a relapse of Crohn’s disease are associated with the clinical course of the disease, World J Gastroenterol, 2008;14:85–9.
36. Consigny Y, Modigliani R, Colombel JF, et al., A simple biological score for predicting low risk of short-term relapse in Crohn’s disease, Inflamm Bowel Dis, 2006;12:551–7.
37. Vermeire S, Review article: genetic susceptibility and application of genetic testing in clinical management of inflammatory bowel disease, Aliment Pharmacol Ther, 2006;24(Suppl. 3):2–10.
38. Weersma RK, Stokkers PC, van Bodegraven AA, et al., Molecular prediction of disease risk and severity in a large Dutch Crohn’s disease cohort, Gut, 2009;58:388–95.
39. Cavanaugh J, NOD2: ethnic and geographic differences, World J Gastroenterol, 2006;12:3673–7.
40. Inohara N, Ogura Y, Nunez G, NODs: a family of cytosolic proteins that regulate the host response to pathogens, Curr Opin Microbiol, 2002;5:76–80.
41. Abreu MT, Taylor KD, Lin YC, et al., Mutations in NOD2 are associated with fibrostenosing disease in patients with Crohn’s disease, Gastroenterology, 2002;123:679–88.
42. Alvarez-Lobos M, Arostegui JI, Sans M, et al., Crohn’s disease patients carrying Nod2/CARD15 gene variants have an increased and early need for first surgery due to stricturing disease and higher rate of surgical recurrence, Ann Surg, 2005;242:693–700.
43. Lesage S, Zouali H, Cezard JP, et al., CARD15/NOD2 mutational analysis and genotype–phenotype correlation in 612 patients with inflammatory bowel disease, Am J Hum Genet, 2002;70:845–57.
44. Adler J, Rangwalla SC, Dwamena BA, et al., The prognostic power of the NOD2 genotype for complicated Crohn’s disease: a meta-analysis, Am J Gastroenterol, 2011;106(4):699–712.
45. Cucchiara S, Latiano A, Palmieri O, et al., Role of CARD15, DLG5 and OCTN genes polymorphisms in children with inflammatory bowel diseases, World J Gastroenterol, 2007;13:1221–9.
46. Papp M, Norman GL, Altorjay I, et al., Utility of serological markers in inflammatory bowel diseases: gadget or magic?, World J Gastroenterol, 2007;13:2028–36.
47. Dubinsky MC, Serologic and laboratory markers in prediction of the disease course in inflammatory bowel disease, World J Gastroenterol, 2010;16:2604–8.
48. Reese GE, Constantinides VA, Simillis C, et al., Diagnostic precision of anti-Saccharomyces cerevisiae antibodies and perinuclear antineutrophil cytoplasmic antibodies in inflammatory bowel disease, Am J Gastroenterol, 2006;101:2410–22.
49. Hoffenberg EJ, Fidanza S, Sauaia A, Serologic testing for inflammatory bowel disease, J Pediatr, 1999;134:447–52.
50. Quinton JF, Sendid B, Reumaux D, et al., Anti-Saccharomyces cerevisiae mannan antibodies combined with antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease: prevalence and diagnostic role, Gut, 1998;42:788–91.
51. Dotan I, Fishman S, Dgani Y, et al., Antibodies against laminaribioside and chitobioside are novel serologic markers in Crohn’s disease, Gastroenterology, 2006;131:366–78.
52. Landers CJ, Cohavy O, Misra R, et al., Selected loss of tolerance evidenced by Crohn’s disease-associated immune responses to auto- and microbial antigens, Gastroenterology, 2002;123:689–99.
53. Targan SR, Landers CJ, Yang H, et al., Antibodies to CBir1 flagellin define a unique response that is associated independently with complicated Crohn’s disease, Gastroenterology, 2005;128:2020–8.
54. Peyrin-Biroulet L, Standaert-Vitse A, Branche J, et al., IBD serological panels: facts and perspectives, Inflamm Bowel Dis, 2007;13:1561–6.
55. Dotan I, New serologic markers for inflammatory bowel disease diagnosis, Dig Dis, 2010;28:418–23.
56. Vasiliauskas EA, Kam LY, Karp LC, et al., Marker antibody expression stratifies Crohn’s disease into immunologically homogeneous subgroups with distinct clinical characteristics, Gut, 2000;47:487–96.
57. Mow WS, Vasiliauskas EA, Lin YC, et al., Association of antibody responses to microbial antigens and complications of small
US GASTROENTEROLOGY & HEPATOLOGY REVIEW
| Page 2
| Page 3
| Page 4
| Page 5
| Page 6
| Page 7
| Page 8
| Page 9
| Page 10
| Page 11
| Page 12
| Page 13
| Page 14
| Page 15
| Page 16
| Page 17
| Page 18
| Page 19
| Page 20
| Page 21
| Page 22
| Page 23
| Page 24
| Page 25
| Page 26
| Page 27
| Page 28
| Page 29
| Page 30
| Page 31
| Page 32
| Page 33
| Page 34
| Page 35
| Page 36
| Page 37
| Page 38
| Page 39
| Page 40
| Page 41
| Page 42
| Page 43
| Page 44
| Page 45
| Page 46
| Page 47
| Page 48
| Page 49
| Page 50
| Page 51
| Page 52
| Page 53
| Page 54
| Page 55
| Page 56
| Page 57
| Page 58
| Page 59
| Page 60
| Page 61
| Page 62
| Page 63
| Page 64
| Page 65
| Page 66
| Page 67
| Page 68
| Page 69
| Page 70
| Page 71
| Page 72
| Page 73
| Page 74
| Page 75
| Page 76