Standard rituximab dose appears inadequate to maintain B cell depletion in AAV

Rituximab maintenance dosing of 500 mg every 6 months may not be enough to maintain B cell depletion in the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), suggests a recent study.

A team of investigators followed a prospective cohort of patients with AAV (n=28) with either granulomatosis with polyangiitis (n=23) or microscopic polyangiitis (n=5) receiving maintenance rituximab therapy in a single tertiary care academic medical centre over a 2-year period. They obtained patient demographics, dosing data, and trough plasma rituximab levels, together with laboratory measures of pharmacologic response, including B cell counts and ANCA titres.

Rituximab dosing information from 94 infusions with 59 trough samples had been collected, with a mean dose of 640±21 mg, dosing interval of 210±88 days, and trough plasma concentration of 622±548 ng/mL. Rituximab trough concentrations correlated with rituximab dose (p=0.60, p<0.0001) and dosing interval (p=–0.55, p<0.0001), while dosing intensity correlated with trough concentrations (p=0.57, p<0.0001).

Higher dosing intensities correlated with undetectable B cell repopulation (p<0.0001), but not negative ANCA titres (p=0.60). When dosing intensities were stratified based on the standard dosing regimen of 500 mg every 6 months (2.4–3.3 mg/d), the regimen correlated with B cell repopulation in eight of 17 doses compared with none of 23 doses (47 percent vs 0 percent) with the high-dose regimen (>3.3 mg/d; p<0.0001).

“Rituximab is effective in the induction and maintenance of remission in AAV,” the investigators said. “However, uncertainty remains regarding the optimal maintenance dosing regimen.”