Predicting Therapeutic Response in Pediatric Ulcerative Colitis—A Journey Towards Precision Medicine

Abstract

Ulcerative colitis (UC) is a disabling disease, characterized by chronic inflammation of the colon, with a rising prevalence worldwide in the pediatric age group. Although UC presents in children with varying severity, disease extent, and comorbidities, initial treatment is essentially uniform, consisting of 5-aminosalicylate drugs with corticosteroid induction for those with moderately to severely active disease. With the advent of anti-tumor necrosis factor (TNF) biologic therapy and several new biologics and small-molecule drugs for UC, precision medicine approaches to treatment are needed to more rapidly achieve sustained remission, restore quality of life, normalize development, and limit exposure to toxic corticosteroids in children with UC. Here, we review available data on clinical, biochemical, histopathologic, and molecular predictors of treatment response in UC. We also address known predictors and special treatment considerations in specific relevant scenarios such as very-early-onset UC, acute severe UC, ileal pouch anal anastomosis, and UC with concomitant primary sclerosing cholangitis. The review concludes with a prediction of how machine learning will integrate multimodal patient data to bring precision medicine to the bedside of children with UC in the future.

Biomarkers in Inflammatory Bowel Diseases: Predicting the Indication and the Effect of Biologics

“…The patient's weight might be a contributing factor to their response to adalimumab and infliximab, as it changes the therapeutic dosage needed [122,123], while the data correlating the patient's age and their response to anti-TNF agents are conflicting in between studies [27]. More specifically, pediatric UC seems to be more diverse, both in its severity and response to therapy, and needs further cohort studies [128] and switching from infliximab to adalimumab [129] or preferably vedolizumab [130,131] has been proven more effective. On the other hand, pediatric CD appears more aggressive, urging the need for earlier escalation to biologic therapy with frequent therapeutic drug monitoring to ensure response, which is ultimately quite efficient [132][133][134].…”

Editorial: achievements and unresolved questions in improving the pharmacokinetics of vedolizumab in adolescents with inflammatory bowel disease—authors' reply

“…With the field entering a new, exciting era of precision medicine, it is important to consider the role of model‐informed dosing to fine‐tune biologics (especially in high‐risk patients). We envision this evolving into using precision‐dosing PK dashboards within the larger context of treat‐to‐target workflows 8 . Importantly, large‐scale implementation of PK dashboards will require a team science approach with multidisciplinary stakeholders, including patients, physicians, pharmacologists and informaticians 9 …”

“…We envision this evolving into using precision-dosing PK dashboards within the larger context of treat-to-target workflows. 8 Importantly, large-scale implementation of PK dashboards will require a team science approach with multidisciplinary stakeholders, including patients, physicians, pharmacologists and informaticians. 9…”

Factors Associated with Response to Systemic Corticosteroids in Active Ulcerative Colitis: Results from a Prospective, Multicenter Trial

“…Secondary endpoints at week 4 are outlined in Table 1. In addition to the Lichtiger score, we assessed a combined endpoint comprising the Lichtiger score and the biomarkers calprotectin and CRP as used in prior publications investigating treatment efficacy in UC [15][16][17][18][19][20][21][22][23].…”