Risk Factors for Disease Behavior Evolution and Efficacy of Biologics in Reducing Progression in Pediatric Patients with Nonstricturing, Nonpenetrating Crohn's Disease at Diagnosis: A Single-Center Experience in Korea
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Background/Aims: Recently, the treatment of Crohn’s disease (CD) has changed to a treat-to-target strategy, in which disease progression is prevented with early intervention. We analyzed the long-term evolution of nonstricturing, nonpenetrating (B1) disease at diagnosis and factors related to disease evolution in pediatric CD. Methods: We retrospectively analyzed 402 patients between 2000 and 2013 who were younger than 18 years and had B1 disease at CD diagnosis. The median follow-up was 6.1 years (range, 1 to 13 years). The cumulative probabilities of developing stricturing (B2) or penetrating (B3) disease and associations between risk factors and disease behavior evolution were evaluated. Results: Among the 402 patients, 75 (18.7%) had B2 or B3 disease by the final follow-up. The cumulative probabilities of disease behavior evolution were 18.3%, 34.3%, and 50.9% at 5, 10, and 13 years, respectively. Patients whose disease progressed had an increased risk of intestinal resection (hazard ratio [HR], 3.61; 95% confidence interval [CI], 2.25 to 6.03; p<0.001). First-degree family history of inflammatory bowel disease (HR, 2.38; 95% CI, 1.07 to 5.28; p=0.032), isolated ileal involvement at diagnosis (HR, 7.55; 95% CI, 1.04 to 15.57; p=0.045), and positive anti-Saccharomyces cerevisiae antibody titers (HR, 2.10; 95% CI, 1.03 to 4.25; p=0.040) were associated with disease behavior evolution. Early treatment with biologics significantly reduced disease progression (HR, 0.46; 95% CI, 0.79 to 3.39; p=0.042). Conclusions: This study suggests that early aggressive therapy should be considered in B1 behavior pediatric CD patients with risk factors of disease evolution to improve long-term outcomes.
Abstract
Background/Aims: Recently, the treatment of Crohn’s disease (CD) has changed to a treat-to-target strategy, in which disease progression is prevented with early intervention. We analyzed the long-term evolution of nonstricturing, nonpenetrating (B1) disease at diagnosis and factors related to disease evolution in pediatric CD. Methods: We retrospectively analyzed 402 patients between 2000 and 2013 who were younger than 18 years and had B1 disease at CD diagnosis. The median follow-up was 6.1 years (range, 1 to 13 years). The cumulative probabilities of developing stricturing (B2) or penetrating (B3) disease and associations between risk factors and disease behavior evolution were evaluated. Results: Among the 402 patients, 75 (18.7%) had B2 or B3 disease by the final follow-up. The cumulative probabilities of disease behavior evolution were 18.3%, 34.3%, and 50.9% at 5, 10, and 13 years, respectively. Patients whose disease progressed had an increased risk of intestinal resection (hazard ratio [HR], 3.61; 95% confidence interval [CI], 2.25 to 6.03; p<0.001). First-degree family history of inflammatory bowel disease (HR, 2.38; 95% CI, 1.07 to 5.28; p=0.032), isolated ileal involvement at diagnosis (HR, 7.55; 95% CI, 1.04 to 15.57; p=0.045), and positive anti-Saccharomyces cerevisiae antibody titers (HR, 2.10; 95% CI, 1.03 to 4.25; p=0.040) were associated with disease behavior evolution. Early treatment with biologics significantly reduced disease progression (HR, 0.46; 95% CI, 0.79 to 3.39; p=0.042). Conclusions: This study suggests that early aggressive therapy should be considered in B1 behavior pediatric CD patients with risk factors of disease evolution to improve long-term outcomes.
참고문헌 (36)
- Roda G, "Crohn’s disease", Nat Rev Dis Primers, 6, pp.22~ (2020)
- Pariente B, "Development of the Crohn’s disease digestive damage score, the Lémann score", Inflamm Bowel Dis, 17, pp.1415~1422 (2011)
- Kim HJ, "Clinical characteristics and long-term outcomes of paediatric Crohn’s disease : a singlecentre experience", J Crohns Colitis, 11, pp.157~164 (2017)
- Fumery M, "Long-term outcome of pediatric-onset Crohn’s disease : a population-based cohort study", Dig Liver Dis, 51, pp.496~502 (2019)
- Colombel JF, "Outcomes and strategies to support a treat-to-target approach in inflammatory bowel disease : a systematic review", J Crohns Colitis, 14, pp.254~266 (2020)
- Jin Soo Moon, "Clinical aspects and treatments for pediatric inflammatory bowel diseases", Intestinal research, 17(1), pp.17~23 (2019), 대한장연구학회[DOI]
- Kerur B, "Biologics delay progression of Crohn’s disease, but not early surgery, in children", Clin Gastroenterol Hepatol, 16, pp.1467~1473 (2018)
- Allen PB, "Moving towards disease modification in inflammatory bowel disease therapy", Curr Opin Gastroenterol, 29, pp.397~404 (2013)
- Jung Ok Shim, "Recent Advance in Very Early Onset Inflammatory Bowel Disease", Pediatric Gastroenterology, Hepatology & Nutrition, 22(1), pp.41~49 (2019), 대한소아소화기영양학회[DOI]
- Levine A, "ESPGHAN revised porto criteria for the diagnosis of inflammatory bowel disease in children and adolescents", J Pediatr Gastroenterol Nutr, 58, pp.795~806 (2014)
- Levine A, "Pediatric modification of the Montreal classification for inflammatory bowel disease : the Paris classification", Inflamm Bowel Dis, 17, pp.1314~1321 (2011)
- Hanauer SB, "Crohn’s disease : step up or top down therapy", Best Pract Res Clin Gastroenterol, 17, pp.131~137 (2003)
- 김경모, "Therapeutic Efficacy of Oral Enteral Nutrition in Pediatric Crohn’s Disease: A Single Center Non-Comparative Retrospective Study", Yonsei Medical Journal, 57(5), pp.1185~1191 (2016), 연세대학교의과대학[DOI]
- Mustafa Adamji, "An overview of the role of exclusive enteral nutrition for complicated Crohn’s disease", Intestinal research, 17(2), pp.171~176 (2019), 대한장연구학회[DOI]
- Lo B, "Changes in disease behaviour and location in patients with Crohn’s disease after seven years of follow-up : a Danish population-based inception cohort", J Crohns Colitis, 12, pp.265~272 (2018)
- Kugathasan S, "Prediction of complicated disease course for children newly diagnosed with Crohn’s disease : a multicentre inception cohort study", Lancet, 389, pp.1710~1718 (2017)
- Lovasz BD, "Evolution of disease phenotype in adult and pediatric onset Crohn’s disease in a population-based cohort", World J Gastroenterol, 19, pp.2217~2226 (2013)
- Dulai PS, "Should we divide Crohn’s disease into ileum-dominant and isolated colonic diseases?", Clin Gastroenterol Hepatol, 17, pp.2634~2643 (2019)
- Hwang SW, "Influence of a positive family history on the clinical course of inflammatory bowel disease", J Crohns Colitis, 10, pp.1024~1032 (2016)
- Dubinsky MC, "Serum immune responses predict rapid disease progression among children with Crohn's disease : immune responses predict disease progression", Am J Gastroenterol, 101, pp.360~367 (2006)
- Dubinsky MC, "Increased immune reactivity predicts aggressive complicating Crohn’s disease in children", Clin Gastroenterol Hepatol, 6, pp.1105~1111 (2008)
- Zhang Z, "Anti-Saccharomyces cerevisiae antibodies associate with phenotypes and higher risk for surgery in Crohn’s disease : a meta-analysis", Dig Dis Sci, 57, pp.2944~2954 (2012)
- Sachar DB, "Is perianal Crohn’s disease associated with intestinal fistulization?", Am J Gastroenterol, 100, pp.1547~1549 (2005)
- Ruemmele FM, "Consensus guidelines of ECCO", ESPGHAN on the medical management of pediatric Crohn’s disease, 2014, pp.8, 1179~1207
- Tarrant KM, "Perianal disease predicts changes in Crohn’s disease phenotyperesults of a population-based study of inflammatory bowel disease phenotype", Am J Gastroenterol, 103, pp.3082~3093 (2008)
- Jin Young Yoon, "Effects of Perianal Involvement on Clinical Outcomes in Crohn’s Disease over 10 Years", Gut and Liver, 12(3), pp.297~305 (2018), 거트앤리버 소화기연관학회협의회
- Kaur M, "Perianal Crohn’s disease is associated with distal colonic disease, stricturing disease behavior, IBD-associated serologies and genetic variation in the JAK-STAT pathway", Inflamm Bowel Dis, 22, pp.862~869 (2016)
- Lee YJ, "Association of TNFSF15polymorphisms in Korean children with Crohn’s disease", Pediatr Int, 57, pp.1149~1153 (2015)
- Van Assche G, "The potential for disease modification in Crohn’s disease", Nat Rev Gastroenterol Hepatol, 7, pp.79~85 (2010)
- Kang B, "Mucosal healing in paediatric patients with moderate-to-severe luminal Crohn’s disease under combined immunosuppression : escalation versus early treatment", J Crohns Colitis, 10, pp.1279~1286 (2016)
- Nuti F, "Prospective evaluation of the achievement of mucosal healing with anti-TNF-α therapy in a paediatric Crohn’s disease cohort", J Crohns Colitis, 10, pp.5~12 (2016)
- Reinink AR, "Endoscopic mucosal healing predicts favorable clinical outcomes in inflammatory bowel disease : a meta-analysis", Inflamm Bowel Dis, 22, pp.1859~1869 (2016)
- Ordás I, "Early use of immunosuppressives or TNF antagonists for the treatment of Crohn’s disease : time for a change", Gut, 60, pp.1754~1763 (2011)
- Walters TD, "Increased effectiveness of early therapy with anti-tumor necrosis factor-α vs an immunomodulator in children with Crohn’s disease", Gastroenterology, 146, pp.383~391 (2014)
- Cosnes J, "Impact of the increasing use of immunosuppressants in Crohn’s disease on the need for intestinal surgery", Gut, 54, pp.237~241 (2005)
- Camus M, "Long-term outcome of patients with Crohn’s disease who respond to azathioprine", Clin Gastroenterol Hepatol, 11, pp.389~394 (2013)