Rituximab serum concentration monitoring predicts B-cell repopulation in children

Measurements of rituximab serum concentration are predictive of future drug concentrations associated with early B-cell repopulation in children with inflammatory diseases, suggests a study.

“This approach may enable earlier rituximab redosing to prevent increased disease activity associated with B-cell repopulation,” said the researchers, who collected blood samples at routine clinical appointments from paediatric patients treated with rituximab.

Starting from 2 weeks onward after rituximab administration, the research team measured rituximab serum concentration, antirituximab antibodies, and CD19+ B cells at each clinical visit. They used the first two serum concentrations, taken >1 month apart, to calculate the half-life and predict future rituximab serum concentrations based on the exponential decay principle. Predicted future levels were compared with actual follow-up measurements (ie, absolute error).

Ten participants (median age 14.0 years, seven female) with antineutrophil cytoplasmic antibodies‒associated vasculitis (n=4), neuroinflammatory disease (n=4), or childhood-onset systemic lupus erythematosus (n=2) were included, contributing a total of 40 samples.

Rituximab had a median half-life of 2.7 weeks. The median absolute error was 0.12 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 weeks.

Five participants had B-cell repopulation at concentrations ≤0.3 μg/mL, and one had positive antidrug antibodies (half-life 1.8 weeks).

“Children are more likely to experience early B-cell repopulation (ie, < 6 months) following rituximab treatment, necessitating redosing as early as 3 months postinfusion,” the researchers said.