The Risk of Severe Infections Following Rituximab Administration in Patients With Autoimmune Kidney Diseases: Austrian ABCDE Registry Analysis.

Balazs Odler,Martin Windpessl,Alexander R Rosenkranz,Daniel Cejka,Martin Wiesholzer,Martin Ursli,Marcell Krall,Karl Lhotta,Kathrin Eller,Marlies Antlanger,Emanuel Zitt,Carina Hebesberger,Andreas Kronbichler,Regina Riedl,Maria Steiner,Marcus Saemann,Philipp Gauckler

doi:10.3389/fimmu.2021.760708

Abstract

ObjectiveTo characterize the incidence, type, and risk factors of severe infections (SI) in patients with autoimmune kidney diseases treated with rituximab (RTX).MethodsWe conducted a multicenter retrospective cohort study of adult patients with immune-related kidney diseases treated with at least one course of RTX between 2015 and 2019. As a part of the ABCDE Registry, detailed data on RTX application and SI were collected. SI were defined by Common Terminology Criteria for Adverse Events v5.0 as infectious complications grade 3 and above. Patients were dichotomized between “nephrotic” and “nephritic” indications. The primary outcome was the incidence of SI within 12 months after the first RTX application.ResultsA total of 144 patients were included. Twenty-five patients (17.4%) presented with SI, mostly within the first 3 months after RTX administration. Most patients in the nephritic group had ANCA-associated vasculitis, while membranous nephropathy was the leading entity in the nephrotic group. Respiratory infections were the leading SI (n= 10, 40%), followed by urinary tract (n=3, 12%) and gastrointestinal infections (n=2, 8%). On multivariable analysis, body mass index (BMI, 24.6 kg/m2 versus 26.9 kg/m2, HR: 0.88; 95%CI: 0.79-0.99; p=0.039) and baseline creatinine (HR: 1.25; 95%CI: 1.04-1.49; p=0.017) were significantly associated with SI. All patients in the nephritic group (n=19; 100%) who experienced a SI received oral glucocorticoid (GC) treatment at the time of infection. Hypogammaglobulinemia was frequent (58.5%) but not associated with SI.ConclusionsAfter RTX administration, impaired kidney function and lower BMI are independent risk factors for SI. Patients with nephritic glomerular diseases having concomitant GC treatment might be at higher risk of developing SI.

Highlights

Severe infections (SI) are a major cause of morbidity and mortality in patients with kidney disease
Eighty-three patients had a nephritic glomerular disease, while 61 patients belonged to the nephrotic group
The Austrian B-Cell Depletion Evaluation (ABCDE) Registry, an Austrian registry focusing on the use of RTX in kidney disease indications, included 144 patients, with the majority of patients having a diagnosis of associated vasculitis (AAV) (54.2%) and membranous nephropathy (MN) (33.3%)

Summary

Introduction

Severe infections (SI) are a major cause of morbidity and mortality in patients with kidney disease. Glomerulopathies, either primary forms or secondary to systemic disorders, exhibit a heightened risk for such complications, which is determined by the underlying disease but to a major extent a direct consequence of immunosuppressive therapy. Rituximab (RTX), a chimeric monoclonal antibody directed against the B cell CD20 antigen, was initially approved for the treatment of hematologic malignancies and subsequently for rheumatoid arthritis. In 2010, its label was expanded for the treatment of ANCA-associated vasculitis (AAV). In parallel, it has become an important off-label agent in the treatment of various forms of autoimmune kidney diseases, such as primary membranous nephropathy (MN), minimal change disease (MCD), and immune-mediated forms of focal segmental glomerulosclerosis (FSGS). While efficacy data of RTX in most glomerular pathologies are still limited to observational studies, several randomized controlled trials (RCT) investigating RTX in MN have recently been published [1,2,3]

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