296. Maintenance of Remission of AAV by Rituximab Based on B-cell Reconstitution vs ANCA Serology (MAINTANCAVAS)
Creators: name: Pravarut Nithagon1
Publisher: name: Zenodo
Year: 2022
Subjects: Vasculitis
ANCA
Abstracts
Giant Cell Arthritis
MPA
GPA
EGPA
Takayasu
IgA vasculitis

description: <strong>Background:</strong> Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disease characterized by small vessel inflammation caused by pathogenic autoantibodies to proteinase 3 (PR3) or myeloperoxidase (MPO). Rituximab (RTX), an anti-CD20 monoclonal antibody, is effective at induction and maintenance of remission. However, RTX is associated with adverse events, including hypogammaglobulinemia, infections, and late-onset of neutropenia. The optimal strategy for long-term maintenance of remission remains unknown. <strong>Methods:</strong> MAINTANCAVAS is an open-label, single center, randomized, two-arm controlled trial (ClinicalTrials.gov Identifier: NCT02749292) aiming to evaluate maintenance of remission strategies that provide the best relapse-free, long-term survival in patients with AAV. An interim analysis was performed of patients with AAV receiving RTX-induced continuous B cell depletion for a minimum of two years who were enrolled and randomized into one of two arms: intermittent B cell depletion with RTX re-dosing upon (1) B cell return ( ≥ 10 B cells/mm3) or (2) upon a significant increase in ANCA titer. B cell and ANCA titer were tested every 3 months. Patients were stratified based on ANCA serotype and duration of preceding B cell depletion. Outcome measures of interest include clinical relapse (defined as BVAS-WG ≥ 2), serologic relapse, total rituximab utilization, serious adverse events and death. <strong>Results:</strong> From May 2016 to June 2020, 115 patients (mean age, 60 years; 48% women) were randomized, 58 to the B cell arm and 57 to the ANCA arm. 53 patients were positive for anti-MPO, and 62 for anti-PR3. The two arms had similar baseline characteristics. Relapse-free survival estimates at month 48 were 95% and 74% in the B cell arm and ANCA arm, respectively (hazard ratio of 3.89, CI 1.41 to 10.71 (P = 0.023 by log-rank). The B cell arm had lower number of clinical relapses (3 vs 12 patients, P&lt;0.05), number of major clinical relapses (2 vs 6 patients, P=0.1623) and serologic relapse (3 vs 13 patients, P&lt;0.01) compared to the ANCA arm. However, the B-cell arm had 4.4x higher rituximab utilization (128 vs 29g) and higher number of serious adverse event (29 vs 16 patients, P&lt;0.05) compared to the ANCA arm. Serious infection appears to be the most common complication in both arms (19/30 vs 7/18, B-cell and ANCA arm respectively), but subjects in the B cell arm experienced higher rate of serious infection (18 vs 6 patients, P&lt;0.05). Covid-19 infection was the most common complication in the B cell arm, accounting for 10/19 of all serious infections and 1 death. <strong>Conclusions:</strong> Rituximab dosing based on B cell return is highly efficacious at preventing relapses compared to rituximab dosing based on ANCA titer. However, the B cell driven strategy was associated with a higher rate of SAEs and Covid-19 complications. The disease control afforded by B cell guided therapy must be balanced against the risk of serious infections. <strong>Disclosures:</strong> None