Objectives: Infliximab, an IgG1 monoclonal antibody (mab), has large inter-individual serum concentration variability. The objective was to determine the extent of the association of baseline albumin concentration and infliximab disposition in patient with ulcerative colitis.
Method: Data from 728 patients with ulcerative colitis from two clinical trials were analyzed to evaluate trends between infliximab pharmacokinetics and serum albumin, or liver or kidney function. Response in the placebo and treated groups were compared by baseline serum albumin concentrations (SAC) groups.
Results: Patients with higher SAC maintained higher infliximab concentrations, lower clearance, and longer half-life than patients with lower SAC. When analyzed by SAC quartiles, patients in the highest quartile had several-fold greater trough infliximab concentrations when compared with those in the lowest quartile. These observations were consistent in both studies and at different dose levels. Generally, clinical response in patients did not vary with SAC when the SAC was within the normal range, apparently because serum infliximab concentrations remained at therapeutic levels. However, patients with SAC lower than the normal laboratory reference range had much lower median serum infliximab concentrations and lower response rates compared with patients within normal SAC. Infliximab pharmacokinetics did not correlate with SGOT or creatinine clearance.
Conclusions: It is hypothesized that the common rescue pathway for both albumin and IgG involving the neonatal Fc receptor may be responsible for the relationship between serum albumin and serum infliximab levels. Baseline albumin level may serve as a valuable and convenient measure of mab pharmacokinetic expectations in these patients.