Evaluating the Long-Term Outcomes of Medical and Surgical Treatments in Fibrostenotic Crohn’s Disease Patients Treated with Anti-TNF/Biologic Therapy

Abstract

Objective: This study analyzed the follow-up findings on hospitalization requirements and clinical activities for fibrostenotic Crohn’s disease (CD) patients who received biological/anti-TNF treatment without undergoing surgery as well as CD patients who were treated medically and surgically.

Materials and Methods: This study compared the Harvey-Bradshaw scores, control colonoscopy results, and hospitalization times regarding the long-term follow-ups for fibrostenotic CD patients who’ve undergone surgery and for those who only received medical treatment. In addition, the study analyzed the factors associated with disease activation.

Results: The study was consisted of 117 patients receiving anti-TNF therapy. Patients who underwent surgery for stenotic CD had a lower one year Harvey-Bradshaw score and shorter hospitalization regarding their long-term follow-up compared to those who did not undergo surgery. Patients who underwent surgery had a lower albumin level (p < 0.001) and developed perianal CD (p = 0.046) less than those who had not undergone surgery. C-reactive protein elevation (p = 0.024) and smoking (p < 0.001) have been associated with disease activity, and the absence of granuloma (p = 0.003) and neural plexitis (p = 0.006) on the surgical specimen was found to be associated with disease activation.

Conclusion: Surgical treatment is seen to improve the quality of life and result in fewer hospitalizations for fibrostenotic CD patients. Also, hypoalbuminemia may be a marker indicating a surgical decision

Keywords

• Crohn Disease
• Anti-TNF Therapy
• Surgical Therapy
• Disease Activation

References

1. 1. Satsangi J, Silverberg MS, Vermeire S, Colombel JF. The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut 2006; 55(6):749-53. [CrossRef] google scholar
2. 2. De Cruz P, Kamm MA, Prideaux L, Allen PB, Desmond PV. Postoperative recurrent luminal Crohn's disease: a systematic review. Inflamm Bowel Dis 2012; 18(4): 758-77. [CrossRef] google scholar
3. 3. Rieder F, Zimmermann EM, Remzi FH, Sandborn WJ. Crohn's disease complicated by strictures: a systematic review. Gut 2013; 62(7): 1072-84. [CrossRef] google scholar
4. 4. Yoo JH, Holubar S, Rieder F. Fibrostenotic strictures in Crohn's disease. Intest Res 2020; 18(4): 379-401. [CrossRef] google scholar
5. 5. Lu C, Baraty B, Lee Robertson H, Filyk A, Shen H, Fung T, et al. Stenosis Therapy and Research (STAR) Consortium. Systematic review: medical therapy for fibrostenosing Crohn's disease. Aliment Pharmacol Ther. 2020; 51(12): 1233-46. [CrossRef] google scholar
6. 6. Rieder F, Bettenworth D, Ma C, Parker CE, Williamson LA, Nelson SA, et al. An expert consensus to standardise definitions, diagnosis and treatment targets for anti-fibrotic stricture therapies in Crohn's disease. Aliment Pharmacol Ther 2018; 48(3): 347-57. [CrossRef] google scholar
7. 7. Murthy SK, Begum J, Benchimol EI, Bernstein CN, Kaplan GG, McCurdy JD, et al. Introduction of anti-TNF therapy has not yielded expected declines in hospitalisation and intestinal resection rates in inflammatory bowel diseases: a population-based interrupted time series study. Gut 2020; 69(2): 274-82. [CrossRef] google scholar
8. 8. Frolkis AD, Dykeman J, Negron ME, Debruyn J, Jette N, Fiest KM, et al. Risk of surgery for inflammatory bowel diseases has decreased over time: a systematic review and meta-analysis of population-based studies. Gastroenterology 2013; 145(5): 9961006. [CrossRef] google scholar

9. 9. Riss S, Schuster I, Papay P, Herbst F, Mittlbock M, Chitsabesan P, et al. Surgical recurrence after primary ileocolic resection for Crohn's disease. Tech Coloproctol 2014; 18(4): 365-71. [CrossRef] google scholar
10. 10. Regueiro M, Velayos F, Greer JB, Bougatsos C, Chou R, Sultan S, et al. American Gastroenterological Association Institute technical review on the management of Crohn's disease after surgical resection. Gastroenterology 2017; 152(1): 277-295. [CrossRef] google scholar
11. 11. Regueiro M, Feagan BG, Zou B, Johanns J, Blank MA, Chevrier M, et al. PREVENT Study Group. Infliximab reduces endoscopic, but not clinical, recurrence of Crohn's disease after ileocolonic resection. Gastroenterology 2016; 150(7): 1568-78. [CrossRef] google scholar
12. 12. Regueiro M, Schraut W, Baidoo L, Kip KE, Sepulveda AR, Pesci M, et al. Infliximab prevents Crohn's disease recurrence after ileal resection. Gastroenterology 2009; 136(2): 441-50. [CrossRef] google scholar
13. 13. Schwartz DA, Loftus EV, Tremaine WJ, Pannaccione R, Sandborn WJ. The natural history of fistulizing Crohn's disease: a population based study. Dig Liver Dis 2000; 32(1): A18. [CrossRef] google scholar
14. 14. Schwartz DA, Loftus EV Jr, Tremaine WJ, Panaccione R, Harmsen WS, Zinsmeister AR, et al. The natural history of fistulizing Crohn's disease in Olmsted County, Minnesota. Gastroenterology. 2002; 122(4): 875-80. [CrossRef] google scholar
15. 15. Chhaya V, Saxena S, Cecil E, Subramanian V, Curcin V, Majeed A, et al. Have perianal surgery rates decreased with the rise in thiopurine use in Crohn's disease? Gut 2014; 63: A176. [CrossRef] google scholar
16. 16. Gomollón F, Dignass A, Annese V, Tilg H, Van Assche G, Lindsay JO, et al. ECCO. 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(1): 3-25. [CrossRef] google scholar
17. 17. Ponsioen CY, de Groof EJ, Eshuis EJ, Gardenbroek TJ, Bossuyt PM, Hart A, et al. Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn's disease: a randomised controlled, open-label, multicentre trial (published correction appears in Lancet Gastroenterol Hepatol 2017; 2(11): 785-92. google scholar
18. 18. Zhou J, Li Y, Gong J, Zhu W. No Association between staging operation and the 5-Year risk of reoperation in patients with Crohn's Disease. Sci Rep 2019; 9(1): 275. [CrossRef] google scholar
19. 19. Cabral VL, de Carvalho L, Miszputen SJ. Importância da albumina sérica na avaliaçao nutricional e de atividade inflamatoria em pacientes com doença de Crohn (Importance of serum albumin values in nutritional assessment and inflammatory activity in patients with Crohn's disease). Arq Gastroenterol 2001; 38(2): 1048. [CrossRef] google scholar
20. 20. Ge X, Liu H, Tang S, Wu Y, Pan Y, Liu W, et al. Preoperative hypoalbuminemia is an independent risk factor for postoperative complications in Crohn's disease patients with normal BMI: A cohort study. Int J Surg. 2020; 79: 294-9. [CrossRef] google scholar
21. 21. Domènech E, Zabana Y, Garcia-Planella E, López San Román A, Nos P, Ginard D, et al. Clinical outcome of newly diagnosed Crohn's disease: a comparative, retrospective study before and after infliximab availability. Aliment Pharmacol Ther 2010; 31(2): 233-9. [CrossRef] google scholar
22. 22. de Groof EJ, Stevens TW, Eshuis EJ, Gardenbroek TJ, Bosmans JE, van Dongen JM, et al. Cost-effectiveness of laparoscopic ileocaecal resection versus infliximab treatment of terminal ileitis in Crohn's disease: the LIR!C Trial. Gut 2019; 68(10): 1774-1780. [CrossRef] google scholar
23. 23. To N, Gracie DJ, Ford AC. Systematic review with meta-analysis: the adverse effects of tobacco smoking on the natural history of Crohn's disease. Aliment Pharmacol Ther 2016; 43(5): 549-61. [CrossRef] google scholar
24. 24. Fagan EA, Dyck RF, Maton PN, Hodgson HJ, Chadwick VS, Petrie A, et al. Serum levels of C-reactive protein in Crohn's disease and ulcerative colitis. Eur J Clin Invest 1982; 12(4): 351-9. [CrossRef] google scholar
25. 25. Boschetti G, Laidet M, Moussata D, Stefanescu C, Roblin X, Phelip G, et al. Levels of fecal calprotectin are associated with the severity of postoperative endoscopic recurrence in asymptomatic patients with Crohn's Disease. Am J Gastroenterol 2015; 110(6): 865-72. [CrossRef] google scholar
26. 26. Yamamoto T, Watanabe T. Surgery for luminal Crohn's disease. World J Gastroenterol 2014; 20(1):78-90. [CrossRef] google scholar
27. 27. Anseline PF, Wlodarczyk J, Murugasu R. Presence of granulomas is associated with recurrence after surgery for Crohn's disease: experience of a surgical unit. Br J Surg 1997; 84(1): 78-82. [CrossRef] google scholar
28. 28. Sokol H, Polin V, Lavergne-Slove A, Panis Y, Treton X, Dray X, et al. Plexitis as a predictive factor of early postoperative clinical recurrence in Crohn's disease. Gut 2009; 58(9): 1218-25. [CrossRef] google scholar