Relapses and serious adverse events during rituximab maintenance therapy in ANCA-associated vasculitis: a multicentre retrospective study

Objectives There are limited real-life data regarding the efficacy and safety of rituximab (RTX) as a remission maintenance agent in microscopic polyangiitis (MPA) and granulomatosis-with-polyangiitis (GPA). We aimed to estimate the incidence and risk factors for relapses, as well for serious adverse events (SAEs) in MPA/GPA patients during RTX maintenance.Methods A retrospective cohort of newly diagnosed/relapsing GPA/MPA patients who received RTX maintenance (>= 1 RTX cycle, >= 6 months follow-up) following complete remission (BVAS version-3 = 0 plus prednisolone <= 7.5 mg/day) with induction regimens. SAEs included serious infections, COronaVIrus-Disease 2019 (COVID-19)-associated hospitalizations, deaths, cardiovascular events, malignancies and hypogammaglobulinemia. The incidence rates (IRs) and relapse-free survival were estimated through Kaplan-Meier plots. Cox regression was conducted to investigate factors associated with the time-to-relapse.Results A total of 101 patients were included: 48% females, 69% GPA, 53% newly diagnosed, median age 63 years. During follow-up (294.5 patient-years, median: 3 RTX cycles), 30 relapses (57% major) occurred among 24 patients (24%, IR 10.2/100 patient-years). Kidney involvement (adjusted hazard ratio/aHR: 0.20; 95% CI: 0.06-0.74, P = 0.016), prior induction with RTX plus CYC (vs RTX monotherapy: aHR = 0.02; 95% CI: 0.001-0.43, P = 0.012) and shorter time interval until complete remission (aHR = 1.07; 95% CI: 1.01-1.14, P = 0.023) were associated with decreased relapse risk. We recorded 17 serious infections (IR 5.8/100 patient-years), 11 COVID-19-associated hospitalizations (IR 3.7/100 patient-years), 4 malignancies (IR 1.4/100 patient-years), 6 cardiovascular events (IR 2/100 patient-years) and 10 deaths (IR 3.4/100 patient-years).Conclusion In this real-world study, relapses during RTX maintenance occurred in approximately 1 out of 4 patients. Kidney involvement, induction with RTX plus CYC, and earlier achievement of complete remission were associated with lower relapse risk. The serious infections rate was consistent with previous reports, whereas an increased rate of COVID-19-associated hospitalizations was observed.