Background: Adalimumab (ADA) is effective in the induction and maintenance of remission in pediatric Crohn's disease (CD). Pharmacokinetics analysis of the IMAgINE-1 study demonstrated that a higher ADA concentration is associated with greater rates of remission. Data remains scarce in terms of which level is predictive of clinical remission in pediatric patients. Moreover, few study, have established the rate of anti-adalimumab antibody (AAA) in this population.
Methods: Aims: To review our experience with therapeutic drug monitoring (TDM) in children with CD and Ulcerative colitis (UC) treated with ADA. The primary objective was to assess the serum levels of ADA in children aged 5–18 years during maintenance. We also aim to 1) establish the rate of AAA in our population and 2) correlate the levels of ADA with clinical response.
Methods: This was a single-center retrospective cohort study. Patients were included if they had at least one serum level of ADA/AAA drawn between June 2014 and November 2016. ADA and AAA analysis were performed in a central lab using a classic ELISA technique. We collected biochemical inflammatory markers drawn the same day or, if missing, at a maximum of two weeks prior to the ADA level. The physician global assessment (PGA) was also recorded if it was done within 4 weeks of the ADA level.
Results: In our database, we identified 95 patients treated with ADA during the study period. Fifty-eight (61%) had at least 1 ADA level drawn (47 with CD, 9 patients with UC and 2 with Indeterminate colitis (IBD-U)). The 2 patients with IBD-U were excluded. Eleven CD patients (19%) had not received infliximab prior to initiating ADA. We collected 97 ADA levels (84% in CD). The overall median ADA level was 12 ug/mL, with a median dose of 0.74 mg/Kg/ injection and at a median frequency of every 14 days. Four patients, all with CD, developed AAA (7.14%). A weekly administration was associated with a higher drug level (14.8 vs 10.1ug/mL, p-value 0.0011). A PGA of remission was linked to 47 (55.3%) levels. An ADA level above 10 correlated with remission according to PGA with a sensitivity of 76% and a specificity of 47.4% (p-value 0.0205). AAA and previous infliximab exposure correlated with a lower in ADA level (p=0.0016 and 0.0448 respectively). Combination therapy improved ADA levels in all patients, but more significantly in patients previously exposed to infliximab (p=0.0369).
Conclusions: ADA measurement is a useful tool in monitoring therapy in children with CD or UC. Aiming for levels above 10 ug/mL could be a target, as it correlates with clinical remission. Combination therapy helps to improve ADA levels. Prospective studies are required to better assess the role of TDM with ADA therapy.