Adalimumab exposure across adult IBD reference models

Berends rounded reference: SC induction and every 2 weeks

Fixed rounded Supplementary Table 1 CL/F, V/F and ka; no covariate, population or individual fit recalculation.

Readouts

Model serum adalimumab concentration · mg/L

Model serum adalimumab concentration; conditional structural calculation.

Exposure (AUC) · mg*day/L

Accumulated model exposure; conditional structural calculation.

Study purpose

• How do the model's key biological readouts change under berends rounded reference: sc induction and every 2 weeks?

Assumptions

• The six rounded Table 1 probes remain fixed reference calculations. Six separate conditional variants add source-specific fixed covariate effects; no original population fit, random effects, residual likelihood, individual prediction or external-validation rankings are recalculated.
• Berends, Marquez, Sanchez and Ternant variants use original fixed-effect sources. FDA uses the validation supplement equation; Vande uses original abstract structural estimates with validation-supplement covariate effects. Full original regulatory/Vande covariate and statistical verification is unavailable.
• All covariates remain constant within each simulation. Original longitudinal covariate histories and patient-level dosing are not reconstructed. The shared nominal comparison regimen is not an individual or original-cohort regimen.
• Binary source categories must be 0 or 1. The preset fixes model selection. Exploratory control bounds are not clinical validation ranges; marginal source ranges do not reconstruct joint patient records.
• The apparent-parameter F=1 convention does not identify absolute bioavailability or true absorbed systemic mass. No separate bioavailability control is supplied.
• Nominal dosing is 160 mg SC at day 0, 80 mg at day 14, then 40 mg every 14 days through day 182. The retained simulation grid uses post-dose at day 0 and pre-dose on later administration days, including day 182. Clinical source samples were collected before the corresponding dose; this simulation convention is not a patient sampling claim.
• Dose input jumps the SC depot; central concentration, accumulated AUC and eliminated apparent amount remain continuous at a bolus.
• Published cohort, parameter and performance values are fixed source references, not patient predictions or recalculated goodness-of-fit metrics.
• Seven retained source-reference identities carry constants only. Their carrier clock is not a paper figure axis or clinical follow-up time; they must be shown as reference views outside the prediction interface.
• Figure 1 digitized components are raster approximations, not patient-level records. Figure 2 red components are source-display observations. Its time scale is hours, clarified by the later published Figure 2; preprint digitization and later unit clarification have distinct provenance. No simulation bands, bootstrap draws or residual arrays are reconstructed.
• Adult IBD source context does not establish pediatric, infant or neonatal support. Fitting, individual dose recommendations and population prediction are unavailable.
• Changing a simulation start applies the supplied initial state there; it does not reconstruct earlier administrations.