Abstract
1. Aims Underdosing of adalimumab can result in non-response and poor
disease control. In this study we investigated the prediction of
adalimumab levels with population pharmacokinetic model-based Bayesian
forecasting early in therapy. This way underexposed non-responders can
possibly be identified early to optimise disease control. 2. Methods A
literature study was performed to identify adalimumab pharmacokinetic
models. With data from a previous pharmacokinetic adalimumab study a
model was evaluated retrospectively. In the prospective phase, a
fit-for-purpose evaluation of the model was performed for rheumatologic
and inflammatory bowel disease patients with peak, trough and control
adalimumab samples obtained by a volumetric absorptive microsampling
technique and administration data from an electronic needle container.
Steady state adalimumab levels were predicted from peak and trough
levels collected after the first adalimumab administration. Predictive
performance was calculated with mean prediction error (MPE) and
normalized root mean square error (RMSE). 3. Results An existing
pharmacokinetic model was selected with external validation for the
prospective phase. Thirty-six patients (22 rheumatologic and 14 IBD)
were included in our study. After stratification for absence of
anti-adalimumab antibodies, the calculated MPE was -2.6% and normalised
RMSE 24.0%. Concordance between predicted and measured adalimumab serum
levels falling within or outside the therapeutic window was 75%. Three
patients (8.3%) developed detectable levels of anti-adalimumab
antibodies. 4. Conclusion This prospective study demonstrates that
adalimumab levels at steady state can be predicted from early samples.
This concept enables early precision dosing at home to guide therapy.