Abstract
BACKGROUND/OBJECTIVE: Rituximab (RTX) has been shown to be effective at maintaining remission in patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), however, the optimal regimen has not been established. The objective of this study was to determine the association between RTX exposure and pharmacological response. METHODS: Thirty patients with GPA (25) and MPA (5) receiving maintenance therapy with RTX were longitudinally followed in a single tertiary care center. Peripheral blood samples were collected at the trough of RTX therapy and plasma RTX concentrations were measured by ELISA. RESULTS: Trough plasma RTX levels greater than 550 ng/mL were associated with B-cell depletion in 100% of the samples analyzed, compared to 51% of samples with levels less than 550 ng/mL (p<0.0001). Trough plasma RTX levels greater than 1,000 ng/mL were associated with hypogammaglobulinemia in 100% of the samples analyzed, compared to 60% of samples with levels less than 1000 ng/mL (p=0.03). There was no association between the peripheral RTX and anti-RTX antibodies. However, the presence of anti-RTX antibodies was associated with a lower risk of hypogammaglobulinemia (83% versus 56%; p=0.04). CONCLUSIONS: Plasma trough RTX level between 550 ng/mL and 1,000 ng/mL is associated with a higher rate of B-cell depletion while minimizing hypogammaglobulinemia in GPA and MPA patients on maintenance RTX therapy. Establishment of target RTX trough levels would allow for a personalized approach to dosing RTX. However, larger and longer-term studies will be necessary to confirm these initial findings.