Biologics Delay Progression of Crohn’s Disease, but Not Early Surgery, in Children

Published:February 24, 2018DOI:

      Background & Aims

      Up to 30% of patients with Crohn's disease (CD) require surgery within the first 5 years from diagnosis. We investigated the recent risk of bowel surgery in an inception cohort of pediatric patients with CD and whether early use of biologics (tumor necrosis factor antagonists) alters later disease course.


      We collected data from the Pediatric Inflammatory Bowel Disease Collaborative Research Group registry on 1442 children (age, ≤16 y) diagnosed with CD from January 2002 through December 2014. Data were collected at diagnosis, 30 days following diagnosis, and then quarterly and during hospitalizations for up to 12 years. Our primary aim was to determine the 10-year risk for surgery in children with CD. Our secondary aim was to determine whether early use of biologics (<3 mo of diagnosis) affected risk of disease progression.


      The 10-year risk of first bowel surgery was 26%. The 5-year risk of bowel surgery did not change from 2002 through 2014, and remained between 13% and 14%. Most surgeries occurred within 3 years from diagnosis. The only predictor of surgery was disease behavior at diagnosis. CD with inflammatory behavior had the lowest risk of surgery compared to stricturing disease, penetrating disease, or both. We associated slowing of disease progression to stricturing or penetrating disease (but not surgery) with early use of biologics, but this effect only became evident after 5 years of disease. Our results indicate that biologics slow disease progression over time (hazard ratio, 0.85; 95% CI, 0.76–0.95).


      In an analysis of data from a registry of pediatric patients with CD, we found that among those with significant and progressing disease at or shortly after presentation, early surgery is difficult to prevent, even with early use of biologics. Early use of biologics (<3 mo of diagnosis) can delay later disease progression to stricturing and/or penetrating disease, but this affect could become evident only years after initial management decisions are made.


      Abbreviations used in this paper:

      CD (Crohn's disease), IBD (inflammatory bowel disease), RISK (Risk Stratification and Identification of Immunogenic and Microbial Markers of Rapid Disease Progression in Children with Crohn's), TNF (tumor necrosis factor)
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        • Khor B.
        • Gardet A.
        • Xavier R.J.
        Genetics and pathogenesis of inflammatory bowel disease.
        Nature. 2011; 474: 307-317
        • Molodecky N.A.
        • Soon I.S.
        • Rabi D.M.
        • et al.
        Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review.
        Gastroenterology. 2012; 142: 46-54
        • Kaplan G.G.
        The global burden of IBD: from 2015 to 2025.
        Nat Rev Gastroenterol Hepatol. 2015; 12: 720-727
        • Shapiro J.M.
        • Zoega H.
        • Shah S.A.
        • et al.
        Incidence of Crohn's disease and ulcerative colitis in Rhode Island: report from the Ocean State Crohn's and Colitis Area Registry.
        Inflamm Bowel Dis. 2016; 22: 1456-1461
        • Gower-Rousseau C.
        • Vasseur F.
        • Fumery M.
        • et al.
        Epidemiology of inflammatory bowel diseases: new insights from a French population-based registry (EPIMAD).
        Dig Liver Dis. 2013; 45: 89-94
        • Solberg I.C.
        • Morten H.V.
        • Ole H.
        • et al.
        Clinical course in Crohn’s disease: results of a Norwegian population-based ten-year follow-up study.
        Clin Gastroenterol Hepatol. 2007; 5: 1430-1438
        • Cosnes J.
        • Nion-Larmurier I.
        • Beaugerie L.
        • et al.
        Impact of the increasing use of immunosuppressants in Crohn’s disease on the need for intestinal surgery.
        Gut. 2005; 54: 237-241
        • Overstraeten A.B.
        • Wolthuis A.
        • D’Hoore A.
        Surgery for Crohn’s disease in the era of biologicals: a reduced need or delayed verdict?.
        World J Gastroenterol. 2012; 18: 3828-3832
        • Chang M.I.
        • Cohen B.L.
        • Greenstein A.J.
        A review of the impact of biologics on surgical complications in Crohn's disease.
        Inflamm Bowel Dis. 2015; 21: 1472-1477
        • Colombel J.F.
        • Sandborn W.J.
        • Reinisch W.
        • et al.
        The SONIC Study Group. Infliximab, azathioprine, or combination therapy for Crohn's disease.
        N Engl J Med. 2010; 362: 1383-1395
        • Feagan B.G.
        • Panaccione R.
        • Sandborn W.J.
        • et al.
        Effects of adalimumab therapy on incidence of hospitalization and surgery in Crohn's disease: results from the CHARM study.
        Gastroenterology. 2008; 135: 1493-1499
        • Colombel J.F.
        • Sandborn W.J.
        • Rutgeerts P.
        • et al.
        Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial.
        Gastroenterology. 2007; 132: 52-65
        • Hanauer S.B.
        • Feagan B.G.
        • Lichtenstein G.R.
        • et al.
        ACCENT I Study Group, maintenance infliximab for Crohn's disease: the ACCENT I randomized trial.
        Lancet. 2002; 359: 1541-1549
        • Cleynen I.
        • Boucher G.
        • Jostins L.
        • et al.
        2015. Inherited determinants of Crohn’s disease and ulcerative colitis phenotypes: a genetic association study.
        Lancet. 2016; 387: 156-167
        • Wolters F.L.
        • Russel M.G.
        • Sijbrandij J.
        • et al.
        Disease outcome of inflammatory bowel disease patients: general outline of a Europe-wide population-based 10-year clinical follow-up study.
        Scand J Gastroenterol Suppl. 2006; 243: 46-54
        • Ramadas A.V.
        • Gunesh S.
        • Thomas G.A.
        • et al.
        Natural history of Crohn’s disease in a population-based cohort from Cardiff (1986-2003): a study of changes in medical treatment and surgical resection rates.
        Gut. 2010; 59: 1200-1206
        • Peyrin-Biroulet L.
        • Oussalah A.
        • Williet N.
        • et al.
        Impact of azathioprine and tumour necrosis factor antagonists on the need for surgery in newly diagnosed Crohn’s disease.
        Gut. 2011; 60: 930-936
        • Hazlewood G.S.
        • Rezaie A.
        • Borman M.
        • et al.
        Comparative effectiveness of immunosuppressants and biologics for inducing and maintaining remission in Crohn's disease: a network meta-analysis.
        Gastroenterology. 2015; 148: 344-354
        • Nuti F.
        • Civitelli F.
        • Bloise S.
        • et al.
        Prospective evaluation of the achievement of mucosal healing with anti-TNF-α therapy in a paediatric Crohn's disease cohort.
        J Crohns Colitis. 2016; 10: 5-12
        • Kugathasan S.
        • Denson L.A.
        • Walters T.D.
        • et al.
        Prediction of complicated disease course for children newly diagnosed with Crohn's disease: a multicentre inception cohort study.
        Lancet. 2017; 389: 1710-1718
        • Frolkis A.D.
        • Dykeman J.
        • Negron M.E.
        • et al.
        Cumulative incidence of first intestinal surgery in adult and pediatric Crohn’s disease: a systematic review and meta-analysis.
        Gastroenterology. 2013; 145: 996-1006
        • Nguyen G.C.
        • Nugent Z.
        • Shaw S.
        • et al.
        Outcomes of patients with Crohn's disease improved from 1988 to 2008 and were associated with increased specialist care.
        Gastroenterology. 2011; 141: 90-97
        • Peyrin-Biroulet L.
        • Harmsen W.S.
        • Tremaine W.J.
        • et al.
        Surgery in a population-based cohort of Crohn's disease from Olmsted County, Minnesota (1970-2004).
        Am J Gastroenterol. 2012; 107: 1693-1701
        • Thia K.T.
        • Sandborn W.J.
        • Harmsen W.S.
        • et al.
        Risk factors associated with progression to intestinal complications of Crohn’s disease in a population-based cohort.
        Gastroenterology. 2010; 139: 1147-1155
        • Burke J.P.
        • Velupillai Y.
        • O’Connell P.R.
        • et al.
        National trends in intestinal resection for Cohn’s disease in the post-biologic era.
        Int J Colorectal Dis. 2013; 28: 1401-1406
        • Debruyn J.C.
        • Soon I.S.
        • Hubbard J.
        • et al.
        Nationwide temporal trends in incidence of hospitalization and surgical intestinal resection in pediatric inflammatory bowel diseases in the United states from 1997 to 2009.
        Inflamm Bowel Dis. 2013; 19: 2423-2432
        • Schaefer M.E.
        • Machan J.T.
        • Kawatu D.
        • et al.
        Factors that determine risk for surgery in pediatric patients with Crohn’s disease.
        Clin Gastroenterol Hepatol. 2010; 8: 789-794
        • Rinawi F.
        • Assa A.
        • Hartman C.
        • et al.
        Incidence of bowel surgery and associated risk factors in pediatric-onset Crohn's disease.
        Inflamm Bowel Dis. 2016; 22: 2917-2923
        • Gupta N.
        • Cohen S.A.
        • Bostrom A.G.
        • et al.
        Risk factors for initial surgery in pediatric patients with Crohn's disease.
        Gastroenterology. 2006; 130: 1069-1077
        • Vernier-Massouille G.
        • Balde M.
        • Salleron J.
        • et al.
        Natural history of pediatric Crohn's disease: a population-based cohort study.
        Gastroenterology. 2008; 135: 1106-1113
        • Whelan G.
        • Farmer R.G.
        • Fazio V.W.
        • et al.
        Recurrence after surgery in Crohn's disease. Relationship to location of disease (clinical pattern) and surgical indication.
        Gastroenterology. 1985; 88: 1826-1833
        • Ryan J.D.
        • Silverberg M.S.
        • Xu W.
        • et al.
        Predicting complicated Crohn's disease and surgery phenotypes, genetics, serology and psychological characteristics of a population-based cohort.
        Aliment Pharmacol Ther. 2013; 38: 274-283
        • Rieder F.
        • Zimmermann E.M.
        • Remzi F.H.
        • et al.
        Crohn’s disease complicated by strictures: a systematic review.
        Gut. 2013; 62: 1072-1084