Risk Factors of Clinical Relapses in Pediatric Luminal Crohn's Disease: A Retrospective Cohort Study

Abstract

INTRODUCTION:There is currently little knowledge on factors associated with the relapse of Crohn's disease (CD) in children. The aims of this study were to describe the risk factors associated with relapse in pediatric CD and the changes in the relapse rate over the past decade.METHODS:Patients younger than 18 years and diagnosed between 2009 and 2019 were included in this retrospective cohort study. Clinical, endoscopic, histological, and laboratory data, as well as induction and maintenance treatments, were collected from the medical records. Survival analyses and Cox regression models were used to assess the impact of these risk factors on relapse.RESULTS:Six hundred thirty-nine patients were included. There was a decrease in the clinical relapse rate over the past decade: 70.9% of the patients diagnosed between 2009 and 2014 relapsed as compared with 49.1% of the patients diagnosed between 2015 and 2019 (P < 0.0001). The following variables were associated with clinical relapse: female sex (adjusted hazard ratio [aHR] = 1.52, P = 0.0007), exposure to oral 5-ASA (aHR = 1.44, P = 0.04), use of immunomodulatory agents compared with tumor necrosis factor-alpha inhibitors (methotrexate aHR = 1.73, P = 0.003; thiopurines aHR = 1.63, P = 0.002), presence of granulomas (aHR = 1.34, P = 0.02) and increased eosinophils on intestinal biopsies (aHR = 1.36, P = 0.02), high levels of C-reactive protein (aHR = 1.01, P < 0.0001) and fecal calprotectin (aHR = 1.08, P < 0.0001), and low serum infliximab levels (aHR = 2.32, P = 0.001).DISCUSSION:Relapse of pediatric CD has decreased in the past decade. The risk of relapse is significantly associated with clinical, endoscopic, histological, and laboratory variables and treatment strategies.

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“…In summary, the quality and efficacy of treatment in pediatric IBD appear to have improved, as children with Crohn’s disease suffer fewer relapses in the last five years than 10–15 years ago [ 47 ]. Early treatment with infliximab or adalimumab should be considered if patients are at high risk of a poor outcome, e.g., Crohn’s with persistently high disease activity despite adequate induction therapy, extensive or pan-enteric manifestation, deep colonic ulcerations, marked growth retardation, severe perianal involvement, radiologically or endoscopically proven structures, the occurrence of fistulas, intestinal perforations, inflammatory conglomerates and/or abscesses, and CMV infections [ 2 ].…”

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“…Multiple studies have identified risk factors for hospitalizations, surgeries, and complications from Crohn’s disease ( 45–48 ), as well as hospitalization or colectomy in ulcerative colitis ( 49 ). For example, a recent retrospective Canadian study found that female sex, 5ASA medication use, immunomodulator use (instead of anti-TNF biologics), granulomas and eosinophils on biopsies, elevated inflammatory markers during clinical remission, and lower serum infliximab titres during clinical remission were associated with clinical relapse ( 50 ). Two recent systematic reviews from the Pediatric IBD-Ahead group summarized the literature on risk prediction for children with Crohn’s disease and ulcerative colitis ( 51 , 52 ).…”

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“…• Un paciente es refractario al tratamiento cuando después de haber excluido la no adherencia o la presencia de otra enfermedad causante de los signos y síntomas, se presenta más de una recaída en el curso de un año, a pesar de un manejo de mantenimiento adecuado con inmunomoduladores, anti-TNF u otros biológicos, o no responde a la terapia de inducción con corticoides o con NEE (68,127,158) . • En un reciente estudio de cohorte restrospectivo, de recaída de ECP luminal, se encontró que las siguientes variables se asociaron con la recaída clínica: sexo femenino, exposición a 5-ASA oral, uso de agentes inmunomoduladores y aumento de eosinófilos en biopsias intestinales, niveles altos de PCR y CF y niveles bajos de infliximab sérico (158) . • En niños se han documentado iguales resultados de los anti-TNF que en adultos, pero en ensayos clínicos no enmascarados.…”