First-Line Treatment for Children and Adolescents With Crohn's Disease

An Analysis Based on Health Insurance Claims Data and Guidelines

For the treatment of children and adolescents with Crohn’s disease (CD), the consensus guidelines of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the European Crohn’s and Colitis Organization (ECCO) represent the highest standard of evidence-based therapy (1). The primary goal is to induce disease remission within the first 90 days of treatment. In patients with luminal CD, exclusive enteral nutrition (EEN) is recommended as first-line treatment (2). EEN is the sole use of a liquid diet to meet 100% (or 120% [2]) of calorie needs, replacing conventional food and drink intake. The aim of this study is to analyze to what extent pediatric patients with CD received EEN.

This work was conducted as part of the German innovation fund project “CED-KQN Big Data - eHealth: Improving the health care of children and adolescents with inflammatory bowel diseases” (CED-KQN: acronym of the German for chronic inflammatory bowel disease, Pediatric Quality Care Network).

Methods

The analysis was based on Germany-wide anonymized data from all branches of the statutory health insurance fund AOK for the period 2014 to 2018, obtained from the Scientific Institute of the AOK (WIdO). Patients under 18 years of age with incident CD were identified by the ICD-10 code K50. To detect new CD cases, we used the algorithm of the case ascertainment definition of Benchimol et al., which includes the numbers of physician visits, hospitalizations, and colonoscopies (3). Outpatient drug treatments were identified by the ATC code (ATC, the Anatomical Therapeutic Chemical classification system), inpatient treatments by the German operation and procedure code (Operationen- und Prozedurenschlüssel, OPS). The treatment categories include immunosuppression (mercaptopurine, azathioprine), 5-ASA (5-aminosalicylic acid; mesalazine, sulfasalazine), biologicals (infliximab, adalimumab), and steroids (budesonide, prednisone, dexamethasone, methylprednisolone). Community-based medical disciplines were identified by the lifetime physician identification number, which is linked to the specialist group.

Results

A total of 1432 children and adolescents with newly diagnosed CD were identified in the AOK data. The median age was 15.0 years (interquartile range 12.0–16.0); 47.4% were female. During the first 90 days of treatment, 259 patients (18.1%) received EEN (Table 1). One hundred twenty-two patients (8.5%) were on immunosuppression only, 142 patients (9.9%) on 5-ASA only, 68 patients (4.7%) on biologicals only, and 91 patients (6.4%) on steroids only. One hundred seventy-six patients (12.3%) received a combination of 5-ASA, biologicals, and steroids without EEN. Treatments not mentioned in the guidelines were given to 560 patients (39.1%).

Table 1

Initial treatment of children and adolescents with Crohn’s disease during the first 3 months

In total, 632 children and adolescents (44.1%) visited a pediatrician in a community medical office, 545 children and adolescents (38.1%) attended a hospital outpatient department, and 473 children and adolescents (33.0%) were seen by a primary care physician (Table 2). Children treated by pediatricians are on average younger than those treated by other physician groups. Table 2 shows the non-inpatient physician groups who treated the patients within the first 90 days. Of the patients treated by a pediatrician, 73.4% received EEN, 45.8% received treatment that did not include EEN, and 28.8% received a form of treatment not recommended in the guidelines.

Table 2

Treatment and physician groups in children and adolescents with Crohn’s disease in non-inpatient care during the first 3 months of treatment

Discussion

Although EEN is recommended as the initial treatment in pediatric patients with CD, the majority did not receive this first-line therapy within the first 90 days. Furthermore, differences among the non-inpatient physician groups with respect to treatment were evident.

EEN is an effective treatment for pediatric Crohn’s disease, but for several reasons its implementation is challenging. Poor adherence due to monotony and the taste of the liquid nutrition is the main barrier. Moreover, there are regional and professional variations in the use of EEN, e.g., with regard to indication, age, duration, choice of formula, exclusivity, and support for the children and adolescents concerned (4). Tolerance of EEN is lower than for partial enteral nutrition (5). Children and adolescents or their parents may reject EEN, requiring use of an alternative form of treatment, e.g., corticosteroids (1).

Summary

Overall, patients in community-based care who received treatment according to the guidelines were most frequently treated by a pediatrician. If more children and adolescents visited pediatricians, the proportion receiving EEN might be increased. To increase adherence to EEN, barriers need to be removed. In this regard, it must be remembered that some primary care physicians have an additional pediatric qualification and that rural regions often have weaker care structures in specialized care. The reasons why patients consult physicians other than pediatricians may therefore lie in regional structural disparities.

The national guidelines of the German Society for Nutritional Medicine were first published in 2014. Therefore, lower adherence to the guidelines was expected in the initial period after publication. However, adherence had increased only slightly by 2018. This is particularly surprising in light of the fact that the use of EEN in luminal CD was recommended in international guidelines before 2014.

With respect to the systematic differences in specialized care, major variability in the quality of care has also been identified internationally. This could be reduced through targeted quality improvement initiatives, e.g., on the basis of disease-specific registries.

Maren Leiz*, Kilson Moon*, Luisa Tischler, Jan de Laffolie, Neeltje van den Berg

Funding

The CED-KQN project is funded by the German Federal Joint Committee (G-BA), CEDKQN, project number VSF17054.

Conflict of interest statement

J.L. has received research funding from Takeda, Abbvie, and Dr. Falk.

The remaining authors declare that no conflict of interests exists.

Manuscript received on 29 August 2022, revised version accepted on 29 December 2022.

Cite this as:
Leiz M, Moon K, Tischler L, de Laffolie J, van den Berg N: First-line treatment for children and adolescents with Crohn’s disease—an analysis based on health insurance claims data and guidelines. Dtsch Arztebl Int 2023; 120: 251–2. DOI: 10.3238/arztebl.m2022.0413

References

1. Ruemmele FM, Veres G, Kolho KL, et al.: Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn‘s disease. J Crohns Colitis 2014; 8: 1179–207.

2. Däbritz J, Gerner P, Enninger A, Claßen M, Radke M: Inflammatory bowel disease in childhood and adolescence—diagnosis and treatment. Dtsch Arztebl Int 2017; 114: 331–8.

3. Benchimol EI, Guttmann A, Griffiths AM, et al.: Increasing incidence of paediatric inflammatory bowel disease in Ontario, Canada: evidence from health administrative data. Gut 2009; 58: 1490–7.

4. Lawley M, Wu JW, Navas-López VM, et al.: Global variation in use of enteral nutrition for pediatric Crohn disease. J Pediatr Gastroenterol Nutr 2018; 67: e22–9.

5. Levine A, Wine E, Assa A, et al.: Crohn’s disease exclusion diet plus partial enteral nutrition induces sustained remission in a randomized controlled trial. Gastroenterology 2019; 157: 440–50.e8.