Monitoramento terapêutico proativo de anti TNF alfa versus reativo em pacientes pediátricos com doenças inflamatórias intestinais: uma revisão de escopo

Abstract

Introduction: Inflammatory bowel diseases (IBD), including Crohn's Disease (CD) and Ulcerative Colitis (UC), have a chronic course and a significant impact on the growth and quality of life of the pediatric population. The use of anti-TNFα biological agents, such as infliximab (IFX) and adalimumab (ADL), has transformed the management of moderate to severe cases. However, therapeutic response is variable, and immunogenicity can compromise treatment effectiveness. Therapeutic Drug Monitoring (TDM) emerges as a strategy for optimizing clinical response, which can be performed reactively or proactively. Objective: To map comparative evidence of proactive versus reactive therapeutic monitoring of IFX and ADL in pediatric patients with IBD, considering serum drug levels, presence of anti-drug antibodies (ADA), clinical data, and therapeutic outcomes. Methods: This is a scoping review conducted according to the methodology recommended by the Joanna Briggs Institute (JBI). The research question was structured according to the PCC model (Population: pediatric patients with CD or UC; Concept: TDM of anti-TNFα; Context: IBD treatment). Studies published between 2019 and 2024 were included, identified in MEDLINE/PubMed, Embase, and Cochrane Library databases. Data were extracted in a standardized manner and analyzed descriptively and by qualitative narrative synthesis. Results: Ten studies were included, including randomized clinical trials, cohorts, and case reports. Proactive TDM demonstrated an association with higher serum levels of IFX and ADL, lower ADA formation, and, in many cases, superior rates of clinical and endoscopic remission. Trials with ADL showed clear superiority of proactive TDM. For IFX, results were more heterogeneous, although suggesting a tendency towards lower hospitalization and greater therapeutic durability. Variability among studies was attributed to methodological and population differences, and defined therapeutic targets. Conclusion: Proactive TDM represents a promising strategy in the therapeutic approach to pediatric IBD, favoring sustained remission, lower immunogenicity, and dose individualization. Despite encouraging evidence, the routine adoption of proactive TDM is still limited by factors such as cost, access, and standardization. Future studies should focus on prospective multicenter trials to validate specific protocols for the pediatric population.