Early Biologic Treatment in Pediatric Crohn's Disease: Catching the Therapeutic Window of Opportunity in Early Disease by Treat-to-Target

Abstract

The emergence of mucosal healing as a treatment goal that could modify the natural course of Crohn's disease and the accumulating evidence showing that biologics are most effective in achieving mucosal healing, along with the success of early treatment regimens for rheumatoid arthritis, have led to the identification of early Crohn's disease and development of the concept of catching the therapeutic window during the early disease course. Thus, an increasing number of pediatric gastroenterologists are adopting an early biologic treatment strategy with or without an immunomodulator. Although early biologic treatment is effective, cost and overtreatment are issues that limit its early use. Currently, there are insufficient data on who will benefit most from early biologics, as well as on who will not need early or even any biologics. For now, top-down biologics should be considered for patients with currently known high-risk factors of poor outcomes. For other patients, close, objective monitoring and accelerating the step-up process by means of a treat-to-target approach seems the best way to catch the therapeutic window in early pediatric Crohn's disease. The individual benefits of immunomodulator addition during early biologic treatment should be weighed against its risks and decision on early combination treatment should be made after comprehensive discussion with each patient and guardian.

Systematic review and meta‐analysis: efficacy and safety of early biologic treatment in adult and paediatric patients with Crohn’s disease

“…A review comparing trials in early CD and rheumatoid arthritis (RA) suggests that the concept of early intervention in other immune‐mediated diseases such as RA is well established and there might be lessons to learn from other chronic inflammatory diseases . This systematic review and meta‐analysis supports findings and hypotheses from several other narrative reviews and overviews …”

Characteristics and Incidence Trends for Pediatric Inflammatory Bowel Disease in Daegu-Kyungpook Province in Korea: a Multi-Center Study

“… 9 Considering the worldwide increasing incidence of IBD in children and adolescents, a healthcare policy for the early detection of IBD seems necessary. 10 …”

The Future of Biosimilars: Maximizing Benefits Across Immune-Mediated Inflammatory Diseases

“…This requires prompt, early treatment and implementation of a treat-to-target approach (top-down or accelerated step-up) to achieve objective endpoints such as endoscopic remission [86][87][88][89][90][91]. Consequently, treatment paradigms are changing to introduce biologics and/or immunomodulators at an earlier stage of disease [87,90,[92][93][94][95]. Numerous guidelines address the role of biologics in IBD treatment [96][97][98][99][100][101][102], generally recommending biologics as a treatment option for steroid-refractory/dependent disease or in patients who are intolerant of, or have contraindications to, conventional therapy.…”

“…Early treatment with biologics is recommended in certain patient populations, including those with a poor prognosis or extensive or severely active disease [96,97,103]. A "window of opportunity" exists in patients with CD, during which intervention with disease-modifying anti-IBD drugs should occur [104] and TNF inhibitor treatment can be much more effective than later use [93]. Available data on early IBD treatment with TNF inhibitors are summarized in Table S1 in the electronic supplementary material.…”