Issue 05

Clinical Question

What risk factors predict clinical relapse in pediatric Crohn’s disease?

Editor’s Bottom Line

Pediatric patients with Crohn’s disease experience high rates of relapse. Predictors of relapse may help to target both intense monitoring and advanced therapy.

Reference

Sassine S, Djani L, Cambron-Asselin C, et al. Risk Factors of Clinical Relapses in Pediatric Luminal Crohn’s Disease, a Retrospective Cohort Study. Am J Gastroenterol. Epub ahead of print Feb 3, 2022; https://journals.lww.com/ajg/Abstract/9900/208.aspx

Synopsis

Given the relative paucity of information on relapse rates in pediatric patients with Crohn’s disease (CD), researchers at several centers in Montreal retrospectively examined data from 639 patients under 18 years of age diagnosed with CD between 2009 and 2019 who had achieved initial clinical response. They documented clinical relapse rates, defined as a change in medical or surgical treatment with an accompanying score ³10 on the short Pediatric Crohn’s Disease Activity Index (sPCDAI).

While disease severity and clinical phenotype did not change over the study period, 69.6% of patients diagnosed between 2009 and 2014 experienced a clinical relapse (median 4 years of follow-up), compared to a 47.8% of those diagnosed between 2015 and 2019 (median 2.3 years follow-up) (p<0.0001). The mean time-to-relapse was 312 days for those diagnosed between 2019 and 2014, compared to 642 days for patients diagnosed between 2015 and 2019.

Multivariate analysis found a number of risk factors for relapse, including female sex (adjusted Hazard Ratio (aHR), 1.52; 95% Confidence Interval [CI], 1.19–1.93; p=0.0007), exposure to oral 5-aminosalyclic acid (ASA) (aHR, 1.44; 95% CI, 1.02–2.04; p=0.04) and use of immunomodulators rather than anti-tumor necrosis factor (TNF) agents (aHR, 1.73 for methotrexate; 95% CI, 1.21–2.48; p=0.003 and aHR for thiopurines, 1.63; 95% CI, 1.21–2.21; p=0.002).

Other variables that predicted clinical relapse included the presence of granulomas on diagnostic biopsies (aHR, 1.34; 95% CI, 1.05–1.71; p=0.02), high eosinophil counts in intestinal biopsies (aHR, 1.36; 95% CI, 1.06–1.75; p=0.02), high C-reactive protein levels (aHR, 1.01; 95% CI, 1.01–1.02; p<0.0001), high fecal calprotectin levels (aHR, 1.08; 95% CI, 1.05–1.11; p<0.0001), and achieving first remission within 12 weeks of diagnosis (aHR, 1.72; 95% CI, 1.33–2.21; p<0.0001).

Other risk factors specifically among those treated with an anti-TNF agent included a high Simple Endoscopic Score for Crohn’s Disease (SES-CD) at the time of diagnosis (aHR, 1.03; 95% CI, 1.01–1.06; p=0.03) and low serum infliximab levels among patients treated with that agent (aHR: 2.32; 95% CI, 1.39–3.88; p<0.001).

Details

Study Design: Retrospective cohort

Funding: Supported by the Fonds de la Recherche du Québec-Santé and the Fondation du CHU Sainte-Justine

Allocation: Not applicable

Setting: Multicenter

Level of Evidence: 2b