Updated European guidance published in the Journal of Crohn’s and Colitis calls for tailoring first-line treatment for children with Crohn’s disease to their risk of poor outcomes. Anti-tumor necrosis factor (anti-TNF) therapy is recommended as first-line treatment for high-risk patients — a group that includes most newly diagnosed children, the authors wrote — while nutritional therapy remains the preferred starting point for those with low-risk luminal disease.
The guideline emphasizes early risk assessment and treatment adjustments based on objective signs of inflammation.
“What I like about this update is that it is not simply a list of drugs; it reflects a broader change in pediatric Crohn’s disease care,” one of the corresponding authors, Marina Aloi, MD, PhD, head of pediatric gastroenterology at Fondazione IRCCS Ca’ Granda Hospital in Milan, Italy, told GI & Hepatology News. “The aim is to prevent damage before it occurs, while remembering that our patients are children and adolescents who are still growing, developing and building their lives outside the clinic. That requires effective treatment, but also nutrition, monitoring, surgery when appropriate, psychological support and shared decision-making.”
The European Crohn’s and Colitis Organisation (ECCO) and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) convened a 27-member panel of pediatric and adult gastroenterologists, a dietitian, and a colorectal surgeon. The panel reviewed research published from January 2018 through October 2024 and conducted targeted searches through June 1, 2025. Eligible evidence included pediatric randomized trials and cohort and case-control studies, along with systematic reviews and meta-analyses in adults. Evidence was graded on the Oxford Centre for Evidence-Based Medicine’s five-level scale, on which level 1 is the strongest. There were two online voting rounds, the second of which added 57 national representatives and outside reviewers, followed by a consensus meeting in October 2025. Statements with at least 80% agreement among the core panel were adopted.
The panel identified risk factors for poor outcomes, including severe growth or pubertal delay, perianal or extensive disease, deep ulcers, strictures, penetrating disease, and failure to achieve clinical and biochemical remission after induction therapy. In a study of 222 previously untreated children cited by the panel, those who achieved corticosteroid-free clinical remission and a normal C-reactive protein level at week 12 had 3.6 times the odds of sustained remission at week 52.
For patients at high risk, the panel recommended starting with infliximab or adalimumab, a recommendation based on level 1 evidence that drew 93% agreement. The panel expressed no clear preference between the two drugs, saying the choice should be guided by shared decision-making. Infliximab should generally be combined with an immunomodulator, the panel said, although infliximab alone may be considered with proactive drug-level monitoring. Adalimumab may be used alone when it is the patient’s first anti-TNF agent.
For patients at low risk, the panel recommended exclusive enteral nutrition as first-line induction therapy, noting that studies have shown a six- to eight-week course to be effective. The Crohn’s disease exclusion diet combined with partial enteral nutrition is an alternative, the panel said. Both options were supported by level 1 evidence, and the recommendation drew 93% agreement. In a 10-week open-label trial of 37 children cited by the panel, 74% of those given exclusive enteral nutrition achieved mucosal healing, compared with 33% of those given corticosteroids, although clinical remission rates were similar.
A dietitian should oversee treatment to support adequate nutrition and reduce the risk of disordered eating, the panel said. If nutritional therapy is not feasible or tolerated, prednisone or prednisolone may be used but should be tapered and stopped within eight to 10 weeks, the panel said. Oral budesonide can also be considered. For children who do not respond to dietary or corticosteroid therapy, the panel recommended anti-TNF therapy. The panel also recommended against using corticosteroids for maintenance.
The recommendations call for treatment goals beyond symptom control. The panel set clinical response as the short-term target; symptomatic remission, a normal C-reactive protein level, and a decrease in fecal calprotectin to an acceptable range as intermediate targets; and endoscopic remission, normalized quality of life, and normal growth as long-term targets. The panel advised evaluating disease activity and extent before making major treatment changes.
The panel recommended proactive drug-level monitoring for infliximab and adalimumab at the end of induction, before treatment reduction, and before an immunomodulator is withdrawn. It also recommended reactive monitoring for incomplete or lost response. The proactive monitoring recommendation was based on level 2 evidence and drew 100% agreement.
In one randomized trial, 82% of children who received proactive adalimumab monitoring achieved sustained corticosteroid-free remission, compared with 48% managed reactively. Another trial found endoscopic remission at 54 weeks in 80% of children who received proactive infliximab monitoring, compared with 57% who received dosing based on clinical response. However, the guideline also cites a meta-analysis of nine studies in patients with inflammatory bowel disease. That analysis found proactive monitoring was no more effective than clinically based dosing, although it could improve drug durability, prevent acute infusion reactions, reduce adverse events, and lower the probability of surgery at lower cost.
For patients who do not respond to anti-TNF therapy, lose response, or cannot tolerate treatment, the panel recommended ustekinumab or a selective interleukin-23 inhibitor such as risankizumab, mirikizumab, or guselkumab. Upadacitinib and, in selected cases, vedolizumab may also be considered. However, the authors noted that pediatric data remain limited and that most of these agents can be prescribed only off-label in many countries.
The authors also called for early surgical consultation, as part of a multidisciplinary approach, for children with stricturing, penetrating, or perianal complications, or when medical therapy fails to control inflammation or restore growth. The panel said endoscopic balloon dilation may be used for accessible strictures measuring up to 5 cm and recommended bowel resection when stricturing or penetrating disease does not respond to medical therapy.
The panel also recommended routinely assessing psychosocial status and general functioning regardless of disease control. It called for addressing fatigue at every visit and providing integrated psychosocial care through multidisciplinary teams.
The authors acknowledged that pediatric data remain limited, particularly for newer advanced therapies and for sequencing after anti-TNF failure. They also noted that regulatory approval, access to therapies, cost, and the feasibility of monitoring must be balanced against efficacy. Many of the perianal and surgical recommendations, along with those on upadacitinib and on combining advanced therapies for highly refractory disease, rested on level 4 or 5 evidence.
ECCO and ESPGHAN funded the guideline. Dr. Aloi reported receiving lecture fees from Pfizer and Nestlé. Sixteen coauthors reported relationships with companies including AbbVie, Janssen, Nestlé, Pfizer, and Takeda; 10 reported none.
Expert Insight
Dr. Aloi spoke with GI & Hepatology News about what the update means for clinical practice.
In your opinion, what are the top 2-3 recommendations from this document?
Dr. Aloi: First, children with features that predict a poor outcome should receive anti-TNF therapy as first-line treatment rather than moving through a prolonged step-up sequence. This is probably the recommendation with the greatest potential to change day-to-day practice.
Second, proactive therapeutic drug monitoring is now recommended for both infliximab and adalimumab, particularly at the end of induction and at key points such as de-escalation or withdrawal of an immunomodulator. In children, pharmacokinetics can be quite variable, so waiting for loss of response before measuring drug exposure is often too late.
Third, treatment should be guided by objective targets. Clinical remission is important, but the long-term target is endoscopic remission, together with normal growth and quality of life. In low-risk luminal disease, nutritional treatment remains the recommended first-line option, and the Crohn’s disease exclusion diet with partial enteral nutrition is now an evidence-based alternative to exclusive enteral nutrition. Other nutritional approaches, such as the Tasty & Healthy diet, have also shown encouraging results in low-risk patients.
As you and your coauthors put together this update, was there a topic, or perhaps more than one, that caused more deliberation than usual?
Dr. Aloi: One of the most discussed issues was how far we should move toward early biologic treatment. Pediatric Crohn’s disease is heterogeneous, and we did not want to replace one rigid algorithm with another. At the same time, most newly diagnosed children have at least one feature associated with a higher risk of an unfavorable course, and the evidence supporting early anti-TNF therapy is strong enough to support its use upfront. The challenge was to make the recommendation strong enough to reflect the evidence, while still leaving room for phenotype, disease severity, family preferences, safety, access, and local circumstances.
What additional research may be needed and what questions remain unanswered on this topic?
Dr. Aloi: The biggest gap is still pediatric-specific evidence for advanced therapies. New drugs are often approved in adults several years before they become available to children, so pediatric gastroenterologists are frequently making decisions using adult trials, pharmacokinetic extrapolation and relatively small real-world pediatric cohorts. We need earlier inclusion of adolescents in drug development, and easier and more appropriate extrapolation of data from adult RCTs, at least for adolescents and older children. We also lack data on optimal therapeutic sequencing after anti-TNF failure in children. This is particularly important in pediatrics, both for efficacy and safety, because we are treating a lifelong disease.