Monitoring in Paediatric IBD

In this context, the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) initiative of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD), published in 2015 [1], identified the targets to be monitored in adult patients with IBD. Those recommendations were also applied to the paediatric population, with necessary adaptations to reflect the specificity of the paediatric context. Mucosal healing (MH) was identified as the main target in both Crohn’s Disease (CD) and Ulcerative Colitis (UC), given its proven association with better long-term outcomes compared with clinical remission alone. At the same time, patients’ clinical remission and reported outcomes were considered as therapeutic goals. Based on the review performed by the STRIDE Steering Committee, it was recommended that at 3–6 months following diagnosis or a major therapeutic change, all patients should be monitored through clinical evaluation and indirect measures of MH (using non-invasive monitoring tools, i.e. faecal calprotectin – FC). Furthermore, it was recommended that after 6–9 months, MH should be evaluated by means of endoscopy (and possibly transmural healing in CD should be assessed using magnetic resonance enterography). Failure to meet the predefined target at any timepoint must lead to therapeutic adjustment and further re-evaluation.

However, regular evaluations of MH require invasive procedures, such as endoscopy, that are not easily accepted by children and families with IBD; thus surrogate markers of inflammation, such as C-reactive protein (CRP) and FC, are commonly used in clinical practice. Several studies have shown a good performance of both tests for prediction of disease relapse, with sensitivity and specificity ranging from 50% to 90%, depending on the cut-off values and clinical scenarios.

In recent years, new insights into disease monitoring in paediatric patients have emerged. First, the results of the STRIDE II programme have been published, which specifically focuses on therapeutic targets in children and in adults [2]. The main recommendations to emerge are (a) the introduction of time-defined targets, specifically clinical response as an immediate target and clinical remission as a medium-term target, and (b) introduction of the restoration of normal growth as a long-term goal for paediatric patients. Mucosal healing was confirmed as a long-term target, and normalization of biomarkers (CRP and FC) as an intermediate one. Moreover, for the first time the authors added quality of life and disability as formal long-term outcomes. The timing for reaching the target is related to the specific drug time of action and monitoring should be performed at different time intervals, aiming at achieving immediate, medium-term and long-term goals depending on the prescribed therapy.

The COVID-19 pandemic has also had a significant impact on management, in that it has highlighted the importance of implementing telemedicine and telemonitoring, including in children with IBD. Data have been published suggesting that paediatric patients, particularly if in remission, can be effectively monitored at home based on clinical symptoms and regular FC measures [3,4].

Finally, the results of the first prospective study comparing proactive versus reactive drug monitoring in paediatric patients under adalimumab showed proactive monitoring to be associated with significantly higher rates of corticosteroid-free clinical remission [5].

In conclusion, disease monitoring is a crucial part of IBD management in children and adults with IBD. Since the routine implementation of the T2T strategy, objective evaluation of the inflammatory state has become the standard for disease monitoring. New technologies have emerged in the last year and virtual care is the “new normal”, which will probably allow easier and, at the same time, more effective monitoring of children with IBD.

References

1. Peyrin-Biroulet L, Sandborn W, Sands BE, et al. Selecting Therapeutic Targets In Inflammatory Bowel Disease (STRIDE): Determining therapeutic goals for treat-to-target. Am J Gastroenterol. 2015;110:1324–38.
2. Turner D, Ricciuto A, Lewis A, et al. STRIDE-II: An update on the Selecting Therapeutic Targets In Inflammatory Bowel Disease (STRIDE) initiative of the International Organization for the Study of IBD (IOIBD): Determining therapeutic goals for treat-to-target strategies in IBD. Gastroenterology. 2021;160:1570–83.
3. Turner D, Huang Y, Martín-de-Carpi J, et al. Corona virus disease 2019 and paediatric inflammatory bowel diseases: Global experience and provisional guidance (March 2020) from the Paediatric IBD Porto Group of European Society of Paediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr. 2020;70:727–33.
4. Arrigo S, Alvisi P, Banzato C, et al. Management of paediatric IBD after the peak of COVID-19 pandemic in Italy: A position paper on behalf of the SIGENP IBD working group. Dig Liver Dis 2021; 53: 183–189
5. Assa A, Matar M, Turner D, et al. Proactive Monitoring of adalimumab trough concentration associated with increased clinical remission in children with Crohn's disease compared with reactive monitoring. Gastroenterology. 2019;157:985–96.