Predicting Outcomes in Pediatric Crohn’s Disease for Management Optimization: Systematic Review and Consensus Statements From the Pediatric Inflammatory Bowel Disease–Ahead Program

Abstract

BACKGROUND & AIMS:A better understanding of prognostic factors within the heterogeneous spectrum of pediatric Crohn's disease (CD) should improve patient management and reduce complications. We aimed to identify evidence-based predictors of outcomes with the goal of optimizing individual patient management. METHODS: A survey of 202 experts in pediatric CD identified and prioritized adverse outcomes to be avoided. A systematic review of the literature with meta-analysis, when possible, was performed to identify clinical studies that investigated predictors of these outcomes. Multiple national and international face-to-face meetings were held to draft consensus statements based on the published evidence. RESULTS: Consensus was reached on 27 statements regarding prognostic factors for surgery, complications, chronically active pediatric CD, and hospitalization. Prognostic factors for surgery included CD diagnosis during adolescence, growth impairment, NOD2/CARD15 polymorphisms, disease behavior, and positive anti-Saccharomyces cerevisiae antibody status. Isolated colonic disease was associated with fewer surgeries. Older age at presentation, small bowel disease, serology (anti-Saccharomyces cerevisiae antibody, antiflagellin, and OmpC), NOD2/ CARD15 polymorphisms, perianal disease, and ethnicity were risk factors for penetrating (B3) and/or stenotic disease (B2). Male sex, young age at onset, small bowel disease, more active disease, and diagnostic delay may be associated with growth impairment. Malnutrition and higher disease activity were associated with reduced bone density. CONCLUSIONS: These evidence-based consensus statements offer insight into predictors of poor outcomes in pediatric CD and are valuable when developing treatment algorithms and planning future studies. Targeted longitudinal studies are needed to further characterize prognostic factors in pediatric CD and to evaluate the impact of treatment algorithms tailored to individual patient risk.

Improving prediction of disease outcome for inflammatory bowel disease: progress through systems medicine

“…Delayed diagnosis [58] Delayed diagnosis [28,44] Black and South Asian ethnicity [58] Long-standing disease duration (>10 years) [32,44] Male gender [58] Male gender [32,44] Growth impairment at diagnosis [50,58] Young age at diagnosis [32,44] Younger age at diagnosis (higher risk for growth impairment) [58] Family history for IBD [32] Older age at diagnosis (e.g. > 13 years; higher risk for complications and for surgery) [58] Disease extension at diagnosis and over time [32] Extensive disease (panenteric inflammation) or deep colonic ulcers [50] Disease severity at diagnosis (assessed clinically through PUCAI score 65 or higher, or through endoscopy) [32] More active disease at diagnosis or over time [58] High histological inflammation score [44] Stricturing disease (demonstrated by endoscopic or radiological examination) at diagnosis, obstructive signs/symptoms, prestenotic dilatation [50,58] Neutrophilic inflammation of stomach and duodenum [32] Penetrating disease (bowel perforations, intraabdominal fistulae, inflammatory masses, and/or abscesses at any time in the course of the disease and not as result of surgical complications) [50,58] Primary sclerosing cholangitis [32] Perianal disease [50,58] C. difficile infection [32] Small bowel disease location (higher risk of growth impairment, stricturing/penetrating complications, multiple surgeries) [44,58] Extra-intestinal manifestations [24] Ileal or ileocolonic disease location (higher risk of surgery, complications, progressive disease, disabling disease) [44] Elevated CRP at diagnosis [24] Colonic disease location (risk of permanent sto...…”

Antibiotics in pediatric inflammatory bowel diseases: a systematic review

“…Consequently, important ethical issues remain with implementing endoscopic reassessments into a trial protocol. Improved clinical scoring systems, often including inflammatory markers like FCP and CRP, as well as patient-reported outcomes measures are currently the topic of considerable research interest [100][101][102].…”

Combination Immunotherapy Use and Withdrawal in Pediatric Inflammatory Bowel Disease—A Review of the Evidence

“…Pragmatically, pediatric patients with more severe disease—especially those diagnosed at a younger age that have extensive disease, growth failure, fistulizing or perianal phenotypes, steroid refractoriness, and previous surgical resection in CD—will benefit most from early combination therapy and subsequent delayed withdrawal ( 1 , 7 ). Predictors of severity of outcomes in PIBD have recently been more clearly delineated ( 58 , 59 ). These risk factors should be carefully considered when determining the weighted risks of relapse vs. continuation of combination therapy at an individual patient level.…”