@article {Springer1718, author = {Jason M. Springer and Ryan S. Funk}, title = {Dose-dependent Pharmacological Response to Rituximab in the Treatment of Antineutrophil Cytoplasmic Antibody-associated Vasculitis}, volume = {48}, number = {11}, pages = {1718--1724}, year = {2021}, doi = {10.3899/jrheum.210361}, publisher = {The Journal of Rheumatology}, abstract = {Objective Rituximab (RTX) is effective in the induction and maintenance of remission in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, uncertainty remains regarding the optimal maintenance dosing regimen. This work evaluates the relationship between variability in RTX dosing and pharmacological response in AAV.Methods A prospective cohort of patients with AAV (n = 28) with either granulomatosis with polyangiitis (n = 23) or microscopic polyangiitis (n = 5) receiving maintenance RTX therapy were followed in a single tertiary care academic medical center over a 2-year period. Patient demographics, RTX dosing information, and trough plasma RTX levels were collected along with laboratory measures of pharmacologic response, including B cell counts and ANCA titers.Results RTX dosing information from 94 infusions with 59 trough samples were collected with a mean {\textpm} SD dose of 640 {\textpm} 221 mg, dosing interval of 210 {\textpm} 88 days, and trough plasma RTX concentration of 622 {\textpm} 548 ng/mL. RTX trough concentrations were associated with RTX dose (ρ = 0.60, P \< 0.0001) and dosing interval (ρ = {\textendash}0.55, P \< 0.0001). RTX dosing intensity (mg/d) was associated with RTX trough concentrations (ρ = 0.57, P \< 0.0001). Higher dosing intensities were associated with undetectable B cell repopulation (P \< 0.0001), but not negative ANCA titers (P = 0.60). Stratification of dosing intensities based on the standard dosing regimen of 500 mg every 6 months (2.4{\textendash}3.3 mg/d) demonstrated that this regimen was associated with B cell repopulation in 8 of 17 doses (47\%) compared to 0 of 23 doses (0\%) with the high-dose regimen (\> 3.3 mg/d; P \< 0.0001).Conclusion RTX maintenance dosing of 500 mg every 6 months may be inadequate to maintain B cell depletion in the treatment of AAV.}, issn = {0315-162X}, URL = {https://www.jrheum.org/content/48/11/1718}, eprint = {https://www.jrheum.org/content/48/11/1718.full.pdf}, journal = {The Journal of Rheumatology} }