ABS0813 CLINICAL IMPACT OF ANTI-RITUXIMAB ANTIBODIES IN SMALL VESSEL VASCULITIS: A MULTICENTRIC RETROSPECTIVE STUDY

<h2>Abstract</h2><h3>Background:</h3> Small vessel vasculitides, including ANCA-associated vasculitis (AAV) and cryoglobulinemic vasculitis (CV), are inflammatory disorders affecting the vasculature and leading to significant organ damage. Rituximab (RTX), a chimeric anti-CD20 monoclonal antibody, has revolutionized treatment strategies, significantly improving disease control and prognosis [1]. However, the emergence of anti-rituximab antibodies (ARAs) has been identified as a major challenge in conditions such as primary membranous glomerulonephritis and rheumatoid arthritis [2]. To date, the role and clinical impact of ARAs in vasculitis remain unknown, making their characterization crucial for optimizing treatment strategies. <h3>Objectives:</h3> To evaluate the impact of ARAs on disease course, treatment response, and prognosis in AAV and CV patients. <h3>Methods:</h3> We retrospectively screened 720 patients from two sources: (1) all consecutive patients with positive ARAs and a confirmed diagnosis of AAV or CV from two reference hospitals specializing in ARA detection, and (2) the French Vasculitis Study Group (GFEV) network. Clinical, immunological, and biological data were analyzed to assess the consequences of ARAs on patient outcomes. <h3>Results:</h3> Thirty-two patients were included, with a median age of 58 years (IQR 42–69), and 75% were female. All CV cases (n=18) were associated with Sjögren's syndrome and positive anti-SSA antibodies, with 59% presenting multiple autoimmune comorbidities. Among AAV cases (n=14), MPO-ANCA was present in 71% and PR3-ANCA in 29%. The most frequent clinical manifestations included cutaneous involvement (59%), peripheral neuropathy (42%), and glomerulonephritis (41%). Patients had received a median of four RTX infusions before ARA detection, with a median interval of nine months (IQR 4–20) between RTX initiation and ARA identification (Figure 1, Panel A). Notably, 66% of patients reported serum sickness-like reactions (rash, arthralgia) during RTX infusions preceding ARA detection. At the time of ARA identification, all patients had detectable CD19+ B cells, along with active disease features, including decreased C4 levels (median 0.01 mg/L, IQR 0.00–0.006), elevated rheumatoid factor (100 mUI/L, IQR 40–200) for CV, and increased CRP levels (40 mg/L, IQR 25–100) (Figure 1, Panel B) for all patients. Following ARA detection, 78% (25/32) required a therapeutic switch, with obinutuzumab being the most frequently used alternative (50%), followed by cyclophosphamide, belimumab, and ofatumumab (9% each). Clinical remission was achieved in 96%, with 92% reaching B-cell depletion after switching to another anti-CD20 agent. One patient died from septic shock. <h3>Conclusion:</h3> This study provides the first comprehensive characterization of ARAs in small vessel vasculitis, highlighting their association with loss of RTX efficacy and persistent B-cell activity. Our findings suggest that ARAs negatively impact disease control, but switching to an alternative anti-CD20 agent may effectively restore B-cell depletion and induce remission. Future analyses will compare ARA-positive and ARA-negative patients to identify risk factors for ARA development and refine treatment strategies. <h3>REFERENCES:</h3> [1] Guillevin, L. <i>et al.</i> Rituximab versus azathioprine for maintenance in ANCA-associated vasculitis. <i>N Engl J Med</i> 371, 1771–1780 (2014). [2] Boyer-Suavet, S. <i>et al.</i> Neutralizing Anti-Rituximab Antibodies and Relapse in Membranous Nephropathy Treated With Rituximab. <i>Front Immunol</i> 10, 3069 (2019). Figure 1 <h3>Acknowledgements:</h3> Groupe Français d'Etude des Vascularites (GFEV). <h3>Disclosure of Interests:</h3> <b>None declared</b>. © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.