Related Experiment Video
Updated: Aug 6, 2026
Dynamic Adhesion Assay for the Functional Analysis of Anti-adhesion Therapies in Inflammatory Bowel Disease
Published on: September 20, 2018
Reactive Therapeutic Drug Monitoring Guides Optimal Management of Adalimumab Failure in Pediatric Crohn's Disease: A
In Sook Jeong1,2, Tae-Gyeong Kim3, Dae Yong Yi2,4
1Department of Pediatrics, Chung-Ang University Gwangmyeong Hospital, Gwangmyeong, Korea.
Insights
Loss of response to adalimumab in pediatric Crohn's disease can be managed with therapeutic drug monitoring and antibody testing. Investigating monogenic disorders is crucial when these strategies fail.
Area of Science:
- Pediatric Gastroenterology
- Immunology
- Pharmacology
Background:
- Biologics, including anti-tumor necrosis factor (TNF) drugs, are increasingly used for pediatric Crohn's disease (CD).
- Loss of response (LOR) to these therapies is a significant clinical challenge.
- Understanding LOR mechanisms is crucial for optimizing treatment strategies.
Purpose of the Study:
- To investigate reactive therapeutic drug monitoring (TDM) and clinical outcomes in pediatric-onset CD patients treated with adalimumab.
- To evaluate the impact of anti-drug antibodies (ADAs) on treatment response.
- To identify factors associated with LOR and guide management decisions.
Main Methods:
- Retrospective study of pediatric CD patients treated with adalimumab (2017-2019).
- Evaluation of reactive TDM levels, ADA presence, and LOR.
- Clinical outcomes followed up until June 2022.
Main Results:
- Thirty-two pediatric patients were analyzed; 14 experienced LOR, and 18 achieved remission.
- Among patients with therapeutic levels and no ADAs, most achieved remission.
- Subtherapeutic levels or presence of ADAs were associated with LOR and biologic switching.
- Two patients with subtherapeutic levels and no ADAs were diagnosed with monogenic inflammatory bowel disease (IBD).
Conclusions:
- Reactive TDM and ADA testing can help categorize LOR mechanisms in pediatric CD.
- These strategies guide dose escalation or biologic switching.
- Exploring underlying monogenic disorders is essential for optimal management when standard strategies fail.
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.
Related Concept Videos
01:29Therapeutic Drug Monitoring: Affecting Factors
01:29Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents
01:24Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF
01:16Therapeutic Drug Monitoring: Overview and Classification
01:26Therapeutic Drug Monitoring: Drug Analysis Methods
01:21Drugs for Treatment of Crohn's Disease in IBD Using Glucocorticoids