아달리무맙을 투여받는 소아 청소년기 크론병 환자에서 단기 점막 치유 및 조직학적 관해를 예측하는 데 있어 치료 약물 모니터링의 잠재적 유용성
Potential Utility of Therapeutic Drug Monitoring of Adalimumab in Predicting Short-term Mucosal Healing and Histologic Remission in Pediatric Crohn’s Disease Patients
Abstract
Background & Aims: There is limited data regarding mucosal healing (MH) and therapeutic drug monitoring in pediatric Crohn’s disease (CD) patients under adalimumab (ADL) treatment. We aimed to investigate the association between ADL trough levels (TLs) and MH, and between ADL TLs and histologic remission (HR) at 4 months from ADL treatment in the pediatric population of CD. Methods: This study was a preliminary study of an ongoing prospective cohort in pediatric CD patients receiving ADL at the Department of Pediatrics, Samsung Medical Center. Moderate-to-severe luminal CD patients who were naïve to biologics were included. Ileocolonoscopies and biopsies as well as clinical activity assessment, laboratory exams, including tests for ADL TLs and antibody to adalimumab (ATA) were performed at 4 months from ADL initiation. MH was defined as a Simple Endoscopic Score for Crohn’s disease (SES-CD) of 0. HR was defined as the complete absence of microscopic inflammation. ADL TLs and ATA status was compared according to MH status at 4 months. Results: Seventeen subjects (13 males, 4 females) were included. At 4 months from ADL initiation, 14 patients (82.4%) were under clinical remission, 8 patients (47.1%) had achieved MH, and 4 patients (23.5%) had achieved HR. 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, 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, P = 0.02). ATA was detected in 1 patient (5.9%). According to receiver operator characteristic curve analysis, the optimal cut-point for predicting MH was 8.76 μg/mL. Conclusions: Serum ADL TLs at 4 months were significantly higher in pediatric CD patients under MH or HR, compared to those who failed to achieve each outcome. Therapeutic drug monitoring may guide in determining short-term MH and HR in the era of treat-to-target.