The Medical Management of Paediatric Crohn’s Disease: an ECCO-ESPGHAN Guideline Update

Abstract

Objective We aimed to provide an evidence-supported update of the ECCO-ESPGHAN guideline on the medical management of paediatric Crohn’s disease [CD]. Methods We formed 10 working groups and formulated 17 PICO-structured clinical questions [Patients, Intervention, Comparator, and Outcome]. A systematic literature search from January 1, 1991 to March 19, 2019 was conducted by a medical librarian using MEDLINE, EMBASE, and Cochrane Central databases. A shortlist of 30 provisional statements were further refined during a consensus meeting in Barcelona in October 2019 and subjected to a vote. In total 22 statements reached ≥ 80% agreement and were retained. Results We established that it was key to identify patients at high risk of a complicated disease course at the earliest opportunity, to reduce bowel damage. Patients with perianal disease, stricturing or penetrating behaviour, or severe growth retardation should be considered for up-front anti-tumour necrosis factor [TNF] agents in combination with an immunomodulator. Therapeutic drug monitoring to guide treatment changes is recommended over empirically escalating anti-TNF dose or switching therapies. Patients with low-risk luminal CD should be induced with exclusive enteral nutrition [EEN], or with corticosteroids when EEN is not an option, and require immunomodulator-based maintenance therapy. Favourable outcomes rely on close monitoring of treatment response, with timely adjustments in therapy when treatment targets are not met. Serial faecal calprotectin measurements or small bowel imaging [ultrasound or magnetic resonance enterography] are more reliable markers of treatment response than clinical scores alone. Conclusions We present state-of-the-art guidance on the medical treatment and long-term management of children and adolescents with CD.

Fool me once… treatment exposure to achieve remission in pediatric IBD

“…The low rate of steroid dependence and improvement of height z-scores for both steroid-and EEN-exposed cohorts suggest an adequate escalation of immune suppression to avoid repeated and prolonged steroid treatment (84% by year 2 in the steroid treatment group vs 51% in EEN-induction group, p = 0.02) This is in keeping with prospective pediatric evidence for the contribution of immunomodulators which is only available for reducing steroid exposure [1]. Scarpato et al also show that after longer follow-up, there is no difference in the subgroups requiring treatment escalation towards anti-tumor necrosis factor (anti-TNF) in the children diagnosed in the era 2003-2013.…”

“…The authors showed that these low trough doses were associated with a higher chance to develop antibodies to infliximab (ATI), which was reduced by co-immunomodulators. The trough levels themselves were not associated with age or co-immunomodulation, suggesting that optimized dosing for patients with higher clearance is achievable and recommendable [1]. Toxicity of higher trough levels has not been shown to date, whereas higher trough levels are associated with improved mucosal healing and outcomes of perianal disease [17,18].…”

“…New guidelines on the treatment of Crohn's disease in children from the European Crohn's and Colitis Organisation (ECCO) and t he European Societ y of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) have recently been published [1]. With the notable exception of dietary studies, most of the evidence base for our current management of pediatric inflammatory bowel disease (IBD) is rooted in adult trials with pediatric modifications following dose-finding or observational studies [2].…”

“…For children with IBD achieving sustained steroid-free remission is incredibly essential. The use of steroids varies greatly between centers and countries and is often more representative of local expertise and bias than based on evidence [1,7,8]. The common theme of these retrospective studies by Scarpato et al [4] and Jongsma et al [5] being how much "treatment exposure" matters: equally for the positive outcomes of mucosal healing and clinical remission as for the adverse effects of steroid-dependence, loss of response, and primary non-response.…”

“…Jongsma et al report on a retrospective study of 215 children treated with infliximab between 2004 and 2019 in centers in Europe and Canada and provide compelling data that younger patients (IBD < 10 years) are not achieving adequate induction dosing with current recommendations which were based on adult index studies [1,5]. At the start of maintenance treatment, 72% of patients < 10 years had trough levels below the therapeutic range (< 5.4 μg/mL).…”