Predictors of improvement in disease activity in childhood and adolescent Crohn's disease: an analysis of age, localization, initial severity and drug therapy - data from the Saxon Registry for Inflammatory Bowel Disease in Children in Germany (2000-2014)

Abstract

The escalating worldwide prevalence of Crohn's disease (CD) among children and adolescents, coupled with a trend toward earlier onset, presents significant challenges for healthcare systems. Moreover, the chronicity of this condition imposes substantial individual burdens. Consequently, the principal objective of CD treatment revolves around rapid inducing remission. This study scrutinizes the impact of age, gender, initial disease localization, and therapy on the duration to achieve disease activity amelioration. Data from the Saxon Pediatric IBD Registry in Germany were analyzed over a period of 15 years. In addition to descriptive methods, logistic and linear regression analyses were conducted to identify correlations. Furthermore, survival analyses and Cox regressions were utilized to identify factors influencing the time to improvement in disease activity. These effects were expressed as Hazard Ratios (HR) with 95% confidence intervals. Data on the clinical course of 338 children and adolescents with CD were available in the registry. The analyses showed a significant correlation between a young age of onset and the severity of disease activity. It was evident that treatment with anti-TNF (Infliximab) was associated with a more favorable prognosis in terms of the time required for improvement in disease activity. Similarly, favorable outcomes were observed with the combination therapies of infliximab with enteral nutrition therapy and Infliximab with immunosuppressants.Conclusion: Our analysis of data from the Saxon Pediatric IBD Registry revealed that the timeframe for improvement of disease activity in pediatric Crohn's disease is influenced by several factors. Specifically, patient age, treatment modality, and initial site of inflammation were found to be significant factors. The study provides important findings that underline the need for individualized treatment.

Keywords: Crohn’s disease; IBD; Pediatrics; Therapy.

Fig. 1

Initial disease activity with respect to: A Gender — There was no statistically significant difference in the initial disease activity between genders (t-test: p-value = 0.10), B Age group — No statistically significant difference in the initial disease activity was observed across distinct age groups (t-test: p-value = 0.39)

Fig. 2

Survival time analysis event= improvement in disease activity. A Stratified by age group A1a median time to improvement 2.41 years (95% CI: 2.19–2.65); A1b 1.80 years (95% CI: 1.70–1.92) log-rank test p<0.001. B Stratified by gender boys median time to improvement 1.93 years (95% CI: 1.81–2.09); girls 2.00 years (95% CI: 1.88–2.16), log-rank test: p= 0.3

Fig. 3

Cox proportional hazard model reduced model: independent variable localization, age classes and gender

Fig. 4

Cox proportional hazard model: independent variable medication (monotherapy)

Fig. 5

Cox proportional hazard model: independent variable medication (combination therapy)

Fig. 6

Duration until improvement in disease activity depending on drug monotherapy and age groups. A Kaplan-Meier plot for treatment with mesalazine (see data in Table 5). B Kaplan-Meier plot for treatment with Steroids (see data in Table 5). C Kaplan-Meier plot for treatment with Immunosuppressants (see data in Table 5). D Kaplan-Meier plot for treatment with Infliximab (see data in Table 5). E Kaplan-Meier plot for treatment with nutrition therapy (see data in Table 5)

Fig. 7

Cox proportional hazard model age group specific: independent variable medication (monotherapy). A Cox proportional hazard model age group A1a. B Cox proportional hazard model age group A1b

Fig. 8

Duration until improvement in disease activity depending on combination therapy and age groups. A Kaplan-Meier plot for Combination treatment with nutritional therapy and mesalazine (see data in Table 6). B Kaplan-Meier plot for Combination treatment with steroids and immunosuppressants (see data in Table 6). C Kaplan-Meier plot for Combination treatment with infliximab and nutritional therapy (see data in Table 6). D Kaplan-Meier plot for Combination treatment with nutritional therapy and steroids (see data in Table 6). E Kaplan-Meier plot for Combination treatment with immunosuppressants and infliximab (see data in Table 6)

Fig. 9

Cox proportional hazard model age group specific: independent variable medication (combination therapy). A Cox proportional hazard model age group A1a. B Cox proportional hazard model age group A1b