J Korean Med Sci.  2020 Apr;35(16):e114. 10.3346/jkms.2020.35.e114.

Potential Utility of Therapeutic DrugMonitoring of Adalimumab in Predicting Short-Term Mucosal Healing and Histologic Remission in Pediatric Crohn's Disease Patients

• Choi SY
• Choi YO
• Choe YH
• Kang B

• KMID: 2500203
• DOI: http://doi.org/10.3346/jkms.2020.35.e114

Abstract

Background
Limited data exist regarding mucosal healing (MH) and therapeutic drug monitoring (TDM) in pediatric Crohn's disease (CD) patients treated with adalimumab (ADL). We aimed to investigate the associations between ADL trough levels (TLs) and MH, and between ADL TLs and histologic remission (HR) at 16 weeks from ADL treatment in pediatric CD patients.
Methods
This was a prospective study on moderate-to-severe luminal pediatric CD patients receiving ADL. Ileocolonoscopies and biopsies, as well as clinical activity assessments, laboratory examinations, including tests for ADL TLs and antibody to ADL, were performed 16 weeks after ADL initiation. MH was defined as a Simple Endoscopic Score for CD of 0. HR was defined as the complete absence of microscopic inflammation.
Results
Seventeen subjects (13 males, 4 females) were included. At 16 weeks from ADL initiation, 14 (82.4%), 8 (47.1%), and 4 (23.5%) patients achieved clinical remission, MH, and HR, respectively. ADL TLs were significantly higher in patients who achieved MH compared to those who did not (13.0 ± 6.5 vs. 6.2 ± 2.6 μg/mL, respectively; P = 0.023) and also significantly higher in patients who achieved HR compared to those who did not (17.9 ± 5.3 vs. 6.8 ± 2.5 μg/mL, respectively; P = 0.02). The optimal TL for predicting MH was 8.76 μg/mL.
Conclusion
Serum ADL TLs at 16 weeks were significantly higher in pediatric patients with CD who achieved MH and HR, respectively. TDM may guide in optimizing treatment efficacy and better target MH in the era of treat-to-target.

Keyword

Therapeutic Drug Monitoring; Mucosal Healing; Adalimumab

Figure

• 

  Fig. 1 ADL TLs according to MH and HR status. (A) Comparison for ADL TLs between CD patients with MH and those without MH (P = 0.023). (B) Comparison for ADL TLs between CD patients with HR and those without HR (P = 0.02).ADL TL = adalimumab trough level, CD = Crohn's disease, MH = mucosal healing, HR = histologic remission.

• 

  Fig. 2 ROC curve of ADL TL in predicting MH.ROC = receiver operating characteristic, PPV = positive predictive value, NPV = negative predictive value, ADL TL = adalimumab trough level, MH = mucosal healing, AUC = area under the curve, CI = confidence interval.

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