313. Rituximab as maintenance therapy for ANCA-associated vasculitides: pooled and long-term analysis of the MAINRITSAN trials
Creators: name: Terrier1, Benjamin
Publisher: name: Zenodo
Year: 2022
Subjects: Vasculitis
ANCA
Abstracts
Giant Cell Arthritis
MPA
GPA
EGPA
Takayasu
IgA vasculitis

description: <strong>Background:</strong> Maintenance therapy after remission induction has been shown to reduce relapse rate in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. The three MAINRITSAN trials have imposed rituximab as gold standard for maintenance treatment. Nevertheless, long-term follow-up of these trials are required to clarify the risk of relapse, as well as rituximab optimal schedule and duration. <strong>Methods:</strong> The MAINRITSAN randomized controlled trials compared fixed 500 mg rituximab infusion at D0, D14, M6, M12, and M18 and azathioprine (MAINRITSAN1); fixed 500 mg rituximab infusion at D0, D14, M6, M12 and M18 (systematic arm) and individually tailored regimen, i.e. when ANCA titer rose and/or circulating CD19+ B lymphocytes reappeared (MAINRITSAN2); and rituximab administered for 18 months to a prolonged treatment with infusions of 500 mg every 6 months of RTX for additional 18 months (MAINRITSAN3) All patients enrolled in these trials were prospectively followed until December 2020 and their data were pooled to analyze relapses and adverse events. Data from the three trials were adjusted for variables identified as associated with relapse to make the data from these studies comparable. <strong>Results:</strong> 277 patients were analyzed with a median follow-up of 73 [51-115] months. 203 patients had granulomatosis with polyangiitis (GPA) (73.3%), 196 (70.8%) had newly diagnosed vasculitis, and 255 (92.0%) were ANCA positive, mainly anti-PR3 (n=170, 61.3%). Factors associated with an increased risk of major relapse were the presence of ENT involvement (hazard ratio 2.00; 95% CI 1.23-3.26) and relapsing patients at inclusion (hazard ratio 1.64; 95% CI 1.04-2.58). After adjustment for prognosis factors, rituximab remained superior to azathioprine in preventing both overall (major and/or minor) and major relapses (hazard ratio 0.29; 95% CI 0.17-0.50 and 0.40; 95% CI 0.22-0.71, respectively). In contrast, individually tailored rituximab administration was associated with an increased risk of major relapse compared with systematic administration (hazard ratio 3.00; 95% CI 1.44-6.27). Finally, prolonged rituximab treatment for 36 months was not associated with a decreased risk of overall or major relapse compared with systematic rituximab administration for 18 months with this extended follow-up update (HR 0.77; 95% CI 0.47-1.26 and 1.16; 95% CI 0.63-2.15, respectively). Long-term follow-up of MAINRITSAN3, by considering the randomization arm in the MAINRITSAN2 trial, showed an increased risk of relapse for patients treated with individually tailored RTX then placebo, compared to patients who received systematic rituximab for 18 months . 68 patients had serious infections during follow-up (24.5%), and prolonged treatment did not increase serious infections rate (hazard ratio 1.14; 95% CI 0.59-2.23). <strong>Conclusion:</strong> This pooled and long-term analysis of patients included in the MAINRITSAN trials confir that rituximab is effective in preventing relapses in ANCA-associated vasculitis, especially with 500 mg infusions every 6 months for 18 months, without increasing the risk of serious infection. Individually tailored administration is associated with an increased risk of major relapse. Finally, extending treatment to 36 months does not appear to be associated with a decreased risk of relapse compared with fixed rituximab administration for 18 months after longer follow-up. <strong>Disclosure: </strong>The authors have no conflicts of interest to declare.