Background and importance Therapeutic drug monitoring is useful to optimise adalimumab therapy in patients with inflammatory bowel disease (IBD).

Aim and objectives The objective of this study was to perform a preliminary pharmacokinetic (PK) model of adalimumab to evaluate covariates potentially responsible for the PK variability in paediatric patients with IBD.

Material and methods A 3 year retrospective multicentre study was performed including children and adolescent (≤ 18 years) diagnosed with IBD and treated with adalimumab. Demographic and clinical data were collected, including serum albumin, C reactive protein and faecal calprotectin. Pre-dose serum samples were carried out before administration. Adalimumab concentrations and anti-adalimumab antibodies (AAA) were determined by ELISA. The model was developed in NONMEM V.7.4 by approximating the non-linear mixed effects models. The first order conditional estimation method with interaction (FOCEI) was used for model building. Concentrations below the lower limit of quantification (LLOQ) were set to LLOQ/2. Body weight (WGT) was included in the PK parameters following an allometric relationship.

Results Twenty-three paediatric patients (10 women) were included, 3 were diagnosed with ulcerative colitis and 20 with Crohn disease. Median age (range) was 14.0 (5–18) years and weight 55.9 (20.4–80) kg. A total of 75 concentrations (2< LLOQ) were determined, with a medium concentration of 10.72 (0.1–24.7) µg/mL. Median (range) serum albumin level was 4.0 (2.8–5.0) g/dL. Only one patient developed AAA. Population PK model (PopPK): a one compartment with first order absorption and elimination described adequately the serum adalimumab concentration–time data. The absorption rate constant was fixed (Ka=0.008/hour) according to Sharma et al. Among the clinical variables analysed, only albumin was significant on the apparent clearance (CL/F). The final PopPK model in the absence of AAA was as defined as: V/F=11.30×(WGT/56 kg) and CL/F (L/day)=0.42×(albumin/4 g/dL)^-2.32 × (WGT/56 kg)^0.75. Covariate analysis reduced the interindividual variability associated with CL (IIVCL) from 34.1% to 21.3%. Proportional residual error estimated was 28.4%.

Conclusion and relevance Adalimumab PK in paediatric patients with IBD was best described by a one compartment model with first order absorption and elimination. WGT was included in the PK parameters following an allometric relationship. Albumin showed statistically significant differences on adalimumab CL/F, explaining 62.5% of its variability.

References and/or acknowledgements 1. Sharma S, et al. Inflamm Bowel Dis 2015;21:783–792.

No conflict of interest.