Search in the Abstract Database

Abstracts Search 2017

* = Presenting author

P674 Potential utility of therapeutic drug monitoring of adalimumab in predicting short-term mucosal healing and histologic remission in paediatric Crohn's disease patients

Kang B.*1, Lee K.1, Choe B.-H.2, Choe Y.H.1

1Samsung Medical Center, Sungkyunkwan University School of Medicine, Department of Pediatrics, Seoul, South Korea 2Kyungpook National University Hospital, Kyungpook National University School of Medicine, Department of Pediatrics, Daegu, South Korea

Background

There is limited data regarding mucosal healing (MH) and therapeutic drug levels in paediatric 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 paediatric population of CD.

Methods

This study was a preliminary analysis of an ongoing prospective cohort in paediatric CD patients receiving ADL at the Department of Pediatrics, Samsung Medical Center. Moderate-to-severe luminal CD patients who were naïve to biologics and receiving ADL before 19 years-old were included. Ileocolonoscopy 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 adalimumab initiation. MH was defined as a Simple Endoscopic Score for Crohn's disease (SES-CD) of 0. Histologic remission (HR) was defined as the complete absence of microscopic inflammation on biopsy specimens obtained from sites of previous and current ulcerations. Adalimumab TLs were compared according to MH status at 4 months.

Results

Table 1. Baseline characterisitics of the subjects (n=17)

Characteristics
Male, n (%)13 (76%)
Diagnosis age, year14.4 (10.8–18.6)
Disease duration to adalimumab, month1.9 (0.2–47)
Adalimumab within 3 month of diagnosis, n (%)15 (88%)
Age at adalimumab initiation, year14.8 (10.9–18.6)
PCDAI prior to adalimumab initiation35 (30–50)
CRP prior to adalimumab initiation, mg/dL1.98 (0.15–7.52)
SES-CD prior to adalimumab initiation19 (6–31)
Concomitant azathioprine, n (%)14 (82%)

Continuous variables are expressed in median (range).

Seventeen subjects were included in this study. At 4 months from ADL initiation, 14 (82.4%) were under clinical remission, 8 (47.1%) had achieved MH, and 4 patients (23.5%) had achieved HR. Dose intensification by interval shortening to every week was done in 1 patient (5.9%). ADL TLs were significantly higher in patients who achieved MH compared to those who did not (13.0±6.5 μg/mL 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 μg/mL vs. 6.8±2.5 μg/mL, p=0.02). ATA was detected in 1 patient (5.9%). According to receiver operator characteristic (ROC) curve analysis, the optimal cut-point for predicting MH was 8.76 μg/mL.

Figure 1. Adalimumab trough levels according to mucosal healing, histologic remission at 4 months.

Figure 2. ROC curve of adalimumab trough levels in predicting mucosal healing at 4 months.

Conclusion

Serum ADL TLs at 4 months were significantly higher in paediatric CD patients under MH or HR, compared to those who failed to achieve each outcome. Future relevant large-scale studies may guide in predicting short-term MH and HR in the era of treat-to-target.