Do Biologics Alter the Natural History of Crohn’s Disease in Children?

An important recent study (B Kerur et al. Clin Gastroenterol Hepatol 2018; 16: 1467-73 & editorial C Ballengee S Kugasthasan 1398-1400) examined the impact of biologic therapies on Crohn’s disease progression and need for surgery in 1442 children (age, ≤16 y) between 2002-14. This study examined data from the Pediatric Inflammatory Bowel Disease Collaborative Research Group registry.

Key findings:

  • Early use of biologics (n=145) was associated with slowing of disease progression (hazard ratio 0.85, CI 0.76-0.95).  Those who received anti-TNF therapy within three months of diagnosis were less likely to develop stricturing (B2) or penetrating (B3) disease.
  • Early anti-TNF therapy did not effect progression to surgery. Surgery rates were 4% at 1 year, 13% at 5 years, and 26% at 10 years.
  • Of those who needed surgery, ~15% already had their first bowel-related surgery in the first 90 days after diagnosis.
  • The study cohort at diagnosis included only 51 with B2 disease, 27 with B3, and 11 with both B2 & B3.  Thus, these three disease phenotypes represented ~6% of the entire cohort.

In the editorial, the authors state that this study “is a sobering reminder that we apparently have not changed the long-term course of CD for our pediatric patients.”  Though, at the same time, they explain how this study had some limitations which could have affected some of the conclusions.

  • In contrast to the RISK study, this study classified patients as B1 who progressed to B2 or B3 in the first 3 months of diagnosis.  Including these patients decreased the chance to show improvement with early biologic therapy.
  • Also, this cohort included a lower percentage of African American patients compared to the RISK study (8% vs 13%).  This also lowered the likelihood of identifying improvement;  these patients are more likely to develop penetrating disease which can be prevented with early biologic therapy (RISK study: Kugasthasan S et al. Lancet 2017; 389: 1710-8).

Also, one other finding of the study was that there was a paradoxical increase in the risk of surgery in the first 5 years in the early biologic group. “This suggests that our practicing pediatric gastroenterologists may have selected the sicker patients to start biologics.”

My take: I think biologics do influence the natural history of Crohn’s disease in children.  However, this study suggests that the magnitude of that alteration is suboptimal.

Related blog post: CCFA update 2017 -RISK study presentation

CCFA: Updates in Inflammatory Bowel Disease 2017 (part 3)

More from our recent CCFA Conference.  My notes may include some errors in transcription and errors of omission.

Subra Kugasthasan -RISK Updates

Dr. Kugasthasan’s lecture was excellent.  He reviewed the typical clinical course of Crohn’s disease; in most patients, it has a remitting and relapsing course.  The goal of the CCFA-sponsored RISK study was to determine how early approaches to treatment affect long-term outcomes.  There is likely a window of opportunity to more favorably affect natural history of the disease. In addition, the goal is to determine whether there are predictive markers of severe disease course.  This prospective study analyzed 913 patients.  In this cohort, 835 remained with B1 (inflammatory) phenotype and 90 developed either B2 (stricturing) phenotype or B3 (penetrating) phenotype.

RISK Study AbstractPrediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study (S Kugathasan et al. Lancet 2017; 389: 17108. DOI:

Key findings:

  • Early TNF therapy reduced the likelihood of penetrating (B3) but not stricturing (B2) disease
  • Based on analysis of genetic expression at baseline, individuals who are likely to develop B2 or B3 disease can be identified. This assay may be available clinically in a few years

Jahnavi Srinivasan -Multi-Disciplinary Approach to IBD A Surgical Perspective

  • Teeuwen PH et al study spans a long period and there have been many changes since that time. The study’s 9% 30-day mortality rate is very high (current Whipple 30-day mortality ~2%)
  • 3-stage surgery most common now for ulcerative colitis due to sicker patients who now need operation
  • Harder to differentiate UC and CD
  • Try to get patients off steroids; this is a key factor in surgical complications. Nutritional support may be helpful though some effects may be mediated by helping with steroid tapering

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) and changes in diet should be confirmed by prescribing physician.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.