The biologic adalimumab is effective for children with Crohn’s disease but little is known about the impact of therapeutic monitoring on clinical outcomes.
Clinically, children with Crohn’s disease (CD) experience similar symptoms to adults and there is some evidence indicating that cases of paediatric CD are increasing, with one study estimating that the highest incidence at 23 per 100,000 person-years occurred in Europe.
Endoscopic evidence of mucosal healing is a valuable therapeutic goal that decreases the risk of disease relapse although little is known about the association between mucosal healing and therapeutic levels of biological treatments such as adalimumab.
This prompted a team from the Department of Paediatrics, Samsung Medical Centre, Korea, to examine the relationship between therapeutic drug monitoring of adalimumab and mucosal healing and clinical remission in paediatric patients with CD.
The team prospectively recruited paediatric patients with CD receiving adalimumab maintenance therapy and who underwent routine endoscopic evaluation of mucosal healing and therapeutic drug monitoring. Monitoring assessments were made at four months and then at years one, two and three.
Findings
A total of 31 children with a mean age of 14.8 years (74% male) were included in the analysis. After one year of treatment, 26 (83.9%) had achieved clinical remission and 17 (54.8%) had evidence of complete mucosal healing. The mean adalimumab trough levels were higher in patients achieving clinical remission compared to those with active disease (7.6 mcg/ml vs 5.1 mcg/ml, remission vs active disease).
Similarly, trough levels of adalimumab were significantly higher in those who achieved mucosal healing after one year (14.2 mcg/ml vs 7.8mcg/ml, mucosal healing vs non-healed, p = 0.03). Although only 23 children remained in the study for three years, among these participants, adalimumab trough levels remained above 10 mcg/ml and a similar proportion of children maintained mucosal healing (64.3%) and clinical remission (92.9%).
Using receiver operating curves, authors calculated that the optimal cut-off adalimumab trough levels to achieve mucosal healing was 8.18 mcg/ml.
In a discussion of these findings, the authors noted how their results demonstrated that mucosal healing rates increased when adalimumab was used over the longer term and that the drug maintained its efficacy. They concluded that there was merit in using therapeutic drug monitoring to guide proactive optimisation of drug levels to achieve the goal of mucosal healing.
Citation
Kim MJ et al. Therapeutic Drug Monitoring of Adalimumab During Long-term Follow-up in Paediatric Patients with Crohn Disease. JPGN 2021;72: 870-6.
