Standard Rituximab Dose May Be Inadequate to Maintain B-Cell Depletion in ANCA-Associated Vasculitis

The standard rituximab maintenance dosing of 500 mg every 6 months may be insufficient to maintain B-cell depletion in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), according to study results presented at the American College of Rheumatology (ACR) Convergence 2021, held virtually from November 3 to 10, 2021. A target rituximab dose of greater than 3.3 mg per day may be required to maintain B-cell depletion.

While rituximab is effective as maintenance therapy for AAV, there is no consensus on the optimal dosing regimen.

Researchers of the current study sought to assess the pharmacologic response of rituximab using different dosing regimens in maintenance therapy of AAV.

Patients with a diagnosis of granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) were enrolled in the study from a tertiary care academic medical center and followed up with prospectively for 2 years during remission therapy with rituximab. Peripheral blood samples were collected before the first maintenance RTX infusion and at regular intervals thereafter.

The primary outcome was pharmacologic response, based on B-cell counts and ANCA titers. Analyses were stratified by dose intensity, with a schedule of 500 mg every 5 to 7 months considered “standard” dosing and other regimens classified as “low” or “high” dosing.

A total of 23 patients with GPA and 5 patients with MPA were enrolled in the study. Mean age at baseline was 60±14 years, and 68% were women. At enrollment, 13 patients tested positive for proteinase 3 ANCA (PR3-ANCA); 14 for myeloperoxidase ANCA (MPO-ANCA); and 1 patient tested ANCA-negative. Mean dose for RTX infusions was 640±221 mg; mean treatment duration was 210±88 days.

Patients with undetectable vs detectable B-cells had a significantly higher mean dose intensity (4.1±2.6 vs 2.7±1.2 mg/d; P <.0001). Patients with both undetectable B-cells and negative ANCA titers also had a higher mean RTX dose than patients with detectable B-cells and positive ANCA titers (4.4±2.5 vs 2.3±0.5 mg/d); however, the difference was only nominally significant (P =.06).

Patients who received the standard vs higher dose of rituximab had significantly more B cells (P =.0003); all patients who received rituximab of greater than 3.3 mg per day had undetectable B cells.

The percentage of patients with undetectable B cells was 100% in the high intensity group compared with 69% and 60% in the low and standard groups, respectively (P =.03). ANCA negativity did not appear to be significantly associated with dose regimen.

According to the researchers, “Standard RTX maintenance dosing intensity of 500 mg every 6 months may be inadequate to maintain B cell depletion in a significant number of patients. A target RTX dose intensity of greater than 3.3 mg [per day] is required to maintain B-cell depletion.”

Reference

Springer J, Funk R. Pharmacological response of rituximab based on dose intensity in maintenance therapy of ANCA-associated vasculitis. Presented at: ACR Convergence 2021; November 3-10, 2021. Abstract 0416.