POS0701 PROSPECTIVE STUDY OF SEVERE INFECTIOUS EVENTS AND IMMUNE RECONSTITUTION AFTER RITUXIMAB IN AUTOIMMUNE DISEASES
Authors: A. Chepy, M. Genin, L. Terriou, C. Chenivesse, D. Staumont-Sallé, H. Zephir, P. Philippe, G. Lefevre, S. Stabler, E. Hachulla, D. Launay, V. Sobanski
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Rituximab (RTX) administration in autoimmune diseases (AID) is associated with severe infectious events (SIE). Frequency of SIE and immune reconstitution (B cells, T cells, and immunoglobulins) after RTX have not yet been comprehensively assessed in a prospective study in patients with various AID. <h3>Objectives:</h3> To explore the impact of RTX on immune system in patients with AID including kinetic evolution of biological parameters, and to estimate the rates of hypogammaglobulinemia (HG), severe infectious events (SIE) and immunoglobulins replacement therapy (IgRT). <h3>Methods:</h3> Patients treated by RTX for AID were included in a prospective study (planned enrollment of 200 patients between May 2019 and May 2022, clinical trial number: NCT03778840). Clinical and biological parameters were recorded at baseline and then every 3 months for one year (M3, M6, M9 and M12). The influence of baseline characteristics on immune reconstitution was assessed using mixed models. <h3>Results:</h3> The anticipated number of inclusions was not met because of the SARS-CoV-2 pandemic, which limited RTX prescription and patients' recruitment. Seventy-two patients were included. There were mostly women (45/72, 62%) presenting with autoimmune cytopenia, connective tissue diseases, organ-specific AID, systemic vasculitis, acquired hemophilia, and other AID. All patients experienced deep B cells depletion and decreased neutrophils count. Both were not influenced by baseline characteristics according to the mixed models. CD4+ and CD8+ T cells count varied over time, with a more profound depletion at M3 and M9 (Figure 1A and B). Mixed model revealed that the use of immunosuppressants (IS) prior to RTX was associated with a more pronounced decrease in CD8+ T cells (p-value: 0.022) and concomitant use of IS at baseline was associated with a more pronounced decrease in CD4+ T cells (p-value: 0.003). We observed a progressive depletion of IgG, IgM, and IgA over time between baseline and M9 (Figure 1C, D and E). HG occurred in 9 patients at M3, 6 at M6, 9 at M9, and 5 at M12. The mixed model revealed that concomitant use of glucocorticosteroids (GC) ≥ 10 mg/day was associated with a more pronounced decrease in IgG rate in the first 6 months (p-value: 0.036). Concomitant use of IS influenced IgM evolution over time (p-value: 0.013). A history of GC ≥ 10 mg/day was associated with a more pronounced decrease of IgA rate during follow-up (p-value: 0.023) and IS use prior to RTX injection influenced the evolution of IgA rate over time (p-value: 0.037). We observed 10 SIE in 9 patients. Three patients received IgIV for immunomodulatory indication (2g/kg), including 2 during the first 3 months of follow-up. <h3>Conclusion:</h3> Our study provides several insights into immune reconstitution in patients treated with RTX for AID. B cell depletion and decreased neutrophils count appeared to be directly linked to RTX administration. IgG levels trajectories were influenced by GC. CD4+ and CD8+ T cells count trajectories appeared to be influenced by IS use. <h3>REFERENCES:</h3> <b>NIL.</b> <h3>Acknowledgements:</h3> Grifols <h3>Disclosure of Interests:</h3> <b>None declared.</b>