Therapeutic Drug Monitoring of Rituximab to Predict Early B-Cell Repopulation in Children With Inflammatory Diseases

Children are more likely to experience early B-cell repopulation (ie, < 6 months) following rituximab treatment, necessitating redosing as early as 3 months post infusion. We hypothesized that rituximab serum concentration measurements can predict the risk of early B-cell repopulation in children and adolescents.

Blood samples were collected at routine clinical appointments from children and adolescents receiving treatment with rituximab. Starting ≥ 2 weeks after rituximab administration, rituximab serum concentration, antirituximab antibodies, and CD19+ B cells were measured at each clinical visit. The first 2 serum concentrations, taken > 1 month apart, were used to calculate the half-life and predict future rituximab serum concentrations based on the exponential decay principle. Predicted future levels were compared to actual follow-up measurements (ie, absolute error).

Ten participants (7 female, median age 14.0 years) with antineutrophil cytoplasmic antibodies-associated vasculitis (n = 4), neuroinflammatory disease (n = 4), or childhood-onset systemic lupus erythematosus (n = 2) contributed 40 samples. The median rituximab half-life was 2.7 (range 1.7-3.5) weeks, and the median absolute error was 0.12 (IQR -0.02 to 0.26) μg/mL, representing a slight overestimation of the predictions. The minimum required rituximab concentration to maintain B-cell depletion (0.55 μg/mL) was reached at a median of 22.2 (range 13.3-28.8) weeks. B-cell repopulation was observed in 5 participants at concentrations ≤ 0.3 μg/mL. One participant had positive antidrug antibodies (half-life 1.8 weeks).

This proof-of-concept study demonstrates that rituximab serum concentration measurements can predict future drug concentrations that are associated with early B-cell repopulation. This approach may enable earlier rituximab redosing to prevent increased disease activity associated with B-cell repopulation.