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

Chrysoula G Gialouri; Aglaia Chalkia; Christos Koutsianas; Katerina Chavatza; Evangelia Argyriou; Alexandros Panagiotopoulos; Anastasios Karamanakos; Aikaterini Dimouli; Christina Tsalapaki; Konstantinos Thomas; Philippos Orfanos; Pagona Lagiou; George Katsikas; Kyriaki Boki; Dimitrios Boumpas; Dimitrios Petras; Dimitrios Vassilopoulos

doi:10.1093/rheumatology/keae409

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

Rheumatology (Oxford). 2024 Aug 6:keae409. doi: 10.1093/rheumatology/keae409. Online ahead of print.

Authors

Chrysoula G Gialouri^{1

2}, Aglaia Chalkia³, Christos Koutsianas¹, Katerina Chavatza⁴, Evangelia Argyriou⁵, Alexandros Panagiotopoulos¹, Anastasios Karamanakos⁶, Aikaterini Dimouli⁶, Christina Tsalapaki¹, Konstantinos Thomas⁴, Philippos Orfanos², Pagona Lagiou², George Katsikas⁶, Kyriaki Boki⁵, Dimitrios Boumpas⁴, Dimitrios Petras³, Dimitrios Vassilopoulos¹

Affiliations

¹ Joint Rheumatology Program, Clinical Immunology-Rheumatology Unit, 2nd Department of Medicine and Laboratory, National and Kapodistrian University of Athens, School of Medicine, General Hospital of Athens "Hippokration", Athens, Greece.
² Department of Hygiene, Epidemiology and Medical Statistics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
³ Nephrology Department, General Hospital of Athens "Hippokration", Athens, Greece.
⁴ Joint Rheumatology Program, Clinical Immunology-Rheumatology Unit, 4th Department of Medicine, National and Kapodistrian University of Athens School of Medicine, Attikon General Hospital, Athens, Greece.
⁵ Rheumatology Unit, Sismanoglio General Hospital, Athens, Greece.
⁶ Department of Rheumatology, "Evangelismos" General Hospital, Athens, Greece.

PMID: 39107924
DOI: 10.1093/rheumatology/keae409

Abstract

Objectives: There are limited real-life data regarding the efficacy and safety of rituximab (RTX) as a remission-maintenance agent in microscopic-polyangiitis (ΜPA) and granulomatosis-with-polyangiitis (GPA). We aimed to estimate the incidence and risk factors for relapses, as well serious-adverse-events (SAEs) in MPA/GPA patients during RTX-maintenance.

Methods: Retrospective cohort of newly-diagnosed/relapsing GPA/MPA patients who received RTX-maintenance (≥1 RTX-cycle, ≥6 months follow-up) following complete-remission (Birmingham-Vasculitis-Activity-Score-version-3 = 0 plus prednisolone ≤7.5 mg/day) with induction regimens. SAEs included serious-infections, COVID-19-associated hospitalizations, deaths, cardiovascular-events, malignancies and hypogammaglobulinemia. Incidence-rates (IR) and relapse-free survival through Kaplan-Meier plots were estimated. Cox-regression was conducted to investigate factors associated with the time-to-relapse.

Results: 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 cyclophosphamide (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 in 1 out of 4 patients. Kidney involvement, induction with RTX plus cyclophosphamide and earlier achievement of complete-remission were associated with lower relapse-risk. Serious-infections rate was consistent with previous reports, whereas an increased rate of COVID19-associated hospitalizations was observed.

Keywords: ANCA-associated vasculitis; infections; maintenance; relapse; rituximab.