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

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/m2versus 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.

Association between different infection profiles and one-year outcomes in ANCA-associated vasculitis: a retrospective study with monthly infection screening

“…Our results suggested that respiratory infection and Gram-negative bacterial and fungal infection during the first 3 months were independently associated with 1-year mortality. Respiratory infection in AAV, as the most common infection type, is almost unanimous in all studies 4–7 10 16 18 19 25–28. Due to the fact that patients with AAV often exhibit pulmonary involvement at the onset, which presents as interalveolar haemorrhage, the function of the endothelium is possibly damaged.…”

“…or cyclophosphamide (CYC)), have been identified as risk factors for infection in patients with AAV. [5][6][7][8][9][10][11][12][13][14][15] These factors are intertwined, which places clinicians in a therapeutic dilemma. A better understanding of infection-related factors helps to balance the benefits and risks associated with treatment.…”

“…In observational studies, approximately 20%–60% of patients with ANCAs had infection episodes during treatment 2–6. According to previous literature, several features, such as older age, more comorbidities, disease severity, renal deficiency at baseline, pulmonary involvement or intensity of therapy (cumulative dose of steroids or cyclophosphamide (CYC)), have been identified as risk factors for infection in patients with AAV 5–15. These factors are intertwined, which places clinicians in a therapeutic dilemma.…”

Overview of infections as an etiologic factor and complication in patients with vasculitides

“…As far as rituximab therapy is concerned, a considerable percentage of patients with AAV may be susceptible to severe infections, with increasing age, impaired renal function, and lower body mass index acting as risk factors [90,91]. Dosing regimens (four-dose and two-dose) do not differ in the rate of incident infections [92].…”

Infections and systemic vasculitis

“…По данным ретроспективного совместного исследования, выполненного в ревматологических центрах Швеции и Мексики, частота тяжелых КИ у больных АНЦА-СВ, получавших РТМ, составила 24% [39]. К факторам риска КИ при лечении РТМ относят увеличение возраста, нарушение функции почек и снижение массы тела [39,40]. Недавно опубликованные результаты байесовского метаанализа РКИ показали, что микофенолата мофетил был, по всей вероятности, наиболее безопасным препаратом в отношении КИ у больных АНЦА-СВ, далее следовали ЦФ, азатиоприн, РТМ и метотрексат [41].…”