POS0860 MAINTENANCE TREATMENT OF ANCA-ASSOCIATED VASCULITIS BEYOND 18 MONTHS OF RITUXIMAB: A PILOT EXPERIENCE
Authors: A. Bartoletti, A. Milanesi, S. Monti, C. Montecucco, P. Delvino
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Rituximab (RTX) is the mainstay of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) treatment for both remission induction and maintenance. Evidence regarding treatment extension beyond the standard 18-month maintenance period is scarce. The latest EULAR guidelines for the management of ANCA-associated vasculitis (AAV) confirm optional RTX extension after maintenance according to relapse risk. Whether to change immunosuppressant (IS), continue biannual RTX, increase timing between doses or tailor infusions according to B cell repopulation is still an object of debate. <h3>Objectives:</h3> To assess the effectiveness and safety of a pilot strategy based on the individual relapse risk profile for AAV maintenance of remission following the 18-month fixed 6-monthly maintenance. <h3>Methods:</h3> GPA and MPA patients who completed 18 months of RTX maintenance (4 doses, 6 months apart) followed up at Policlinico San Matteo, Pavia, were assigned to a personalised maintenance continuation regimen based on the risk of future relapse. Patients with history of severe relapse were considered at high risk of relapse and continued 6-monthly RTX (RTX6m), independently from AAV subtype and ANCA specificity at baseline. GPA and/or PR3-positive had intermediate risk and received spaced 12-monthly RTX. MPO-positive MPA patients were at low risk and stopped RTX to commence another IS. A group of patients who stopped RTX upon maintenance completion without starting another IS was included for comparison. <h3>Results:</h3> Twenty-two patients were enrolled: 13 were females (59.1%), mean age 57±13 years. Fourteen (63.6%) had GPA, 12 (54.5%) were PR3+. Upon 18-month maintenance completion, patients continued treatment according to relapse risk: 7 (31.8%) remained on RTX6m, 9 (40.9%) underwent RTX spacing, 3 (13.6%) stopped RTX in favour of azathioprine (2) or mycophenolate (1), and 3 stopped RTX without starting any IS. Median individualised treatment duration was 23 months (IQR 13-36), with 12 patients being followed up for ≥24 months. Outcomes along time are displayed in Table 1 and Figure 1. None of the RTX6m patients relapsed (Figure 1A). Indeed, they experienced severe infections and hypogammaglobulinemia more often than the other groups (Figure 1B,C). One patient with hypogammaglobulinemia progressed to severe hypogammaglobulinemia at 4 months. There was no significant difference in ANCA seroconversion between the groups, but RTX6m patients showed a delayed CD19+ repopulation compared to others (Figure 1D). Notably, RTX6m median daily glucocorticoid (GC) dose was the highest at both 12 and 24 months (Table 1). In contrast, patients on RTX spacing had early GC&lt;5mg/day tapering. Only one patient relapsed with nasal crusting at 20 months. Spacing patients had the lowest infection rates among all groups, although one patient developed severe hypogammaglobulinemia at 16 months. The IS group had no AAV relapses, intermediate GC doses and infectious events. Two treatment-free patients had a minor relapse (arthralgia, 28 months; proteinuria and arthralgia, 21 months). There were no differences in terms of VDI increase based on the treatment group. No severe relapses, deaths or progression to end-stage renal disease occurred. <h3>Conclusion:</h3> Tailoring maintenance treatment according to individual relapse risk seems effective in balancing disease activity control with the risk of infection. Spacing can be offered to patients with intermediate relapse risk to minimise the degree of immunosuppression and its drawbacks, while biannual RTX continuation beyond the standard maintenance period should be reserved to cases at highest risk. Efficacy and safety of spaced RTX infusions for AAV maintenance should be assessed in larger cohort studies and randomised controlled trials. <b>Table 1.</b> Outcomes at 12 and 24 months of individualised maintenance treatment groups. <b>REFERENCES: NIL.</b> <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>