Management of paediatric ulcerative colitis, part 1: Ambulatory care-An updated evidence-based consensus guideline from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition and the European Crohn's and Colitis Organisation

Abstract

Objectives: Despite advances in the management of ambulatory paediatric ulcerative colitis (UC), challenges remain as many patients are refractory to therapy and some require colectomy. The aim of these guidelines is to provide an update on optimal care for UC through detailed recommendations and practice points.

Methods: These guidelines are an update to those published in 2018 and are a joint effort of the Paediatric IBD Porto group of European Society of Paediatric Gastroenterology, Hepatology and Nutrition and the European Crohn's and Colitis Organisation. An extensive literature search with subsequent evidence appraisal using the Oxford methodology was performed, followed by three online voting sessions and a consensus face-to-face meeting. Thirty-nine recommendations and 77 practice points were endorsed by the 25 experts with at least an 84% consensus rate.

Results: Robust evidence-based recommendations and detailed practice points are provided. In addition to reemphasising and updating the role of more 'traditional' UC therapies, these guidelines outline optimising the use of antitumour necrosis factor therapies and integrating newer biologics and small molecules, as well as supportive therapy, to improve outcomes and provide an updated management algorithm. Measurement and monitoring tools and decision aids are provided, and additional aspects, including nutritional support, extraintestinal manifestations, pouchitis, inflammatory bowel disease-unclassified and patient support, are discussed. Some aspects, including surgery and thromboprophylaxis, are covered in the acute severe UC guidelines.

Conclusions: These guidelines serve as an aid in managing children with UC through a combination of evidence-based recommendations and more practical practice points in the ambulatory setting.

Keywords: Paediatric Ulcerative Colitis Activity Index; biologics; children; inflammatory bowel disease‐unclassified; thiopurines.

Figure 1

Summary flowchart of managing paediatric ulcerative colitis (UC). Medical therapies in UC are divided into those that induce remission (5‐aminosalicylate [5‐ASA], corticosteroids, antitumour necrosis factor [TNF] therapy and calcineurin inhibitors) and those that maintain remission (5‐ASA, thiopurines, anti‐TNF therapy and off‐label therapies). (1) Assessment of active disease and differential diagnosis are detailed in the text and in Figure 2. (2) 5‐ASA is usually dosed 50–70 mg/kg/day, up to 4.8 g daily. Once daily dosing may be as effective as twice daily dosing. (3) 5‐ASA enemas (25 mg/kg; 1 g daily is as effective as higher doses) are usually more effective than steroid enemas. (4) Lack of improvement (i.e., Paediatric Ulcerative Colitis Activity Index [PUCAI] decrease of <20 points) after 7–14 days or increase in PUCAI ≥ 20 points at any time should prompt treatment escalation. (5) Effort should be made to reduce steroid exposure; start taper within 1–2 weeks if response is seen and limit taper to 7 weeks (Table 1). Steroid dependency should be avoided. (6) See guidelines on management of acute severe colitis. (7) Response is defined as a drop in PUCAI of at least 20 points. However, the ultimate goal of induction therapy is complete remission (Figure 3). (8) For example, previous intolerance or resistance to steroids, or when infliximab is indicated anyway for maintenance treatment after failing thiopurines. (9) Measuring thiopurine methyltransferase (TPMT; genotyping or enzymatic activity) should be tested at baseline; serum thiopurine metabolites (6‐thioguanine [6‐TGN] and 6‐methylmercaptopurine [MMP]) assist in optimising thiopurine dosing. (10) Infliximab should be administered with an immunomodulator and usually at a higher dose of 10 mg/kg; the dose can be reduced after achieving remission, guided by serum trough concentration. Stepping down to thiopurine (in naïve patients) or 5‐ASA may be considered in selected cases, and after a period of sustained deep remission. (11) Decisions on the use of off‐label therapies should include the lack of approved indication in children and analysis of risk‐benefit considerations; these are best provided in an experienced centre with monitoring based on adult guidelines. (12) Colectomy is always an option in refractory patients and should not be seen as a last resort. It is best practice to initiate informed, multidisciplinary discussions on surgery before decision time.

Figure 2

Diagnostic workup for suspected UC. ¹Useless in case of frank mucoid‐bloody diarrhoea. CD, Crohn disease; FC, faecal calprotectin; IBDU, inflammatory bowel disease unclassified; IUS, intestinal ultrasound; MRE, magnetic resonance enterography; UC, ulcerative colitis; WCE, wireless capsule endoscopy.

Figure 3

Algorithm for monitoring paediatric ulcerative colitis (UC) during the maintenance phase. ¹Quality of life scores and patient‐reported outcomes (PROs), such as TUMMY‐UC, are encouraged as part of disease assessment. ²In asymptomatic patients, consider repeating FC measurements (at least 2–4 weeks apart) before endoscopic evaluation or therapy change. ³Proceeding to sigmoidoscopy/colonoscopy should preferably be based on at least two independent calprotectin measurements. Endoscopic re‐evaluation is also recommended before major treatment modifications and when it is not clear if symptoms are disease‐related. ⁴The decision whether to escalate therapy based on a Mayo 0 or 1 endoscopic findings should be individualised, based on the current treatment (e.g., it is easier to increase mesalamine dose or add rectal therapy than starting thiopurines), symptoms, and extent (short Mayo 1 segment may be closely monitored whereas extensive disease may require escalation). FC, faecal calprotectin; PUCAI, paediatric ulcerative colitis activity index.

Figure 4

TDM decision tree for infliximab treatment. Note that at Week 14 or later, higher trough concentrations (>8 mcg/mL) may be needed to fully respond. *Remeasure anti‐drug antibodies shortly before the next administration to differentiate between transient and persistent antibodies.

Figure 5

Iron deficiency and anaemia screening in paediatric UC. Anaemia screening tools mainly evaluate iron stores and inflammation, although inflammation impact on routine iron deficiency (ID) markers poses significant challenges in distinguishing IDA from ACD in clinical practice. Other blood markers of ID, serum soluble transferrin receptor (sTfR) and sTfR/log ferritin ratio, have been recently demonstrated to outperform routine markers, but a lack of standardisation, costs and availability limit their clinical use currently. ACD, anaemia of chronic diseases; CRP, C‐reactive protein; ESR, erythrocyte sedimentation rate; IDA, iron deficiency anaemia; MCV, mean corpuscular volume; TSAT, transferrin saturation;

Figure 6

Iron deficiency and anaemia management in paediatric ulcerative colitis. *OI should be taken on an empty stomach in a mildly acidic medium, such as ascorbic acid, to increase absorption further. **Intravenous iron (IVI) should be considered as the first choice in severe anaemia. Blood transfusion (BT) should be evaluated in acute cases with rapid Hb drop and/or clinically unstable. IVI should be administered subsequently to BT to replenish iron storages. ***Treatment monitoring should include phosphate levels in patients who have received IVI formulations at risk for causing hypophosphatemia. ACD, anaemia of chronic diseases; Hb, haemoglobin; ID, iron deficiency; IDA, iron deficiency anaemia; OI, oral iron.

Figure 7

Endoscopic screening and surveillance for colorectal cancer (CRC) in children with colonic IBD. In patients who have no colonic involvement or disease limited to the rectum, no further IBD‐specific surveillance is indicated. *Including post‐liver transplant. **In patients who have not undergone surgery. ***Dye‐based chromoendoscopy (DCE), virtual electronic chromoendoscopy (VCE), high definition white light endoscopy (HD‐WLE).