Reactive Therapeutic Drug Monitoring Guides Optimal Management of Adalimumab Failure in Pediatric Crohn's Disease: A Real-World Single-Center Experience.
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PURPOSE: Although biologics, including anti-tumor necrosis factor (TNF) drugs, are increasingly used for treating pediatric Crohn's disease (CD), the potential loss of response (LOR) to these drugs requires attention. This retrospective study investigated reactive therapeutic drug monitoring (TDM) and the clinical course of pediatric-onset CD in patients treated with adalimumab. METHODS: Patients aged <18 years diagnosed with CD and treated with adalimumab were enrolled in this study. Reactive TDM levels, presence of anti-drug antibodies (ADAs), and LOR were evaluated from 2017 to 2019, and clinical outcomes were followed up until June 2022. RESULTS: Thirty-two pediatric patients with CD were enrolled: 14 in the LOR group and 18 in the remission group. The median ages at CD diagnosis and first adalimumab injection were 13 and 14 years, respectively. The median duration of adalimumab injection was 12.5 months. Among 7 patients with therapeutic trough levels (TLs) and undetectable ADAs, 5 achieved clinical remission with continued adalimumab, whereas 2 remained refractory and subsequently switched to alternative biologics. Among 5 patients with subtherapeutic TLs (<5 µg/mL) and undetectable ADAs, 3 eventually underwent a switch to other biologic agents despite interval shortening, while the remaining 2 were ultimately diagnosed with monogenic inflammatory bowel disease (IBD) after further genetic evaluation. CONCLUSION: Reactive TDM and ADA categorizes the mechanisms of LOR to adalimumab in pediatric CD, guiding appropriate dose escalation or biologic switching. When these strategies fail, exploring underlying monogenic disorders is essential for optimal management.