Trimethoprim–sulfamethoxazole prophylaxis prevents severe/life-threatening infections following rituximab in antineutrophil cytoplasm antibody-associated vasculitis

Kronbichler, Andreas; Kerschbaum, Julia; Gopaluni, Seerapani; Tieu, Joanna; Alberici, Federico; Jones, Rachel; Smith, Rona; Jayne, David

doi:10.1136/annrheumdis-2017-212861

Cited by 116 publications

(102 citation statements)

References 22 publications

(32 reference statements)

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“…Co-trimoxazole prophylaxis was not associated with a reduced rate of SI in our cohort. However, its use has been shown to be protective in other similar conditions such as ANCA-associated vasculitis (AAV) [35,36].…”

Section: Discussionmentioning

confidence: 99%

Severe Infection in Anti-Glomerular Basement Membrane Disease: A Retrospective Multicenter French Study

Caillard

Vigneau

Hazzan

et al. 2020

JCM

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In patients presenting with anti-glomerular basement membrane (GBM) disease with advanced isolated kidney involvement, the benefit of intensive therapy remains controversial due to adverse events, particularly infection. We aim to describe the burden of severe infections (SI) (requiring hospitalization or intravenous antibiotics) and identify predictive factors of SI in a large cohort of patients with anti-GBM disease. Among the 201 patients (median [IQR] age, 53 [30–71] years) included, 74 had pulmonary involvement and 127 isolated glomerulonephritis. A total of 161 SI occurred in 116 patients during the first year after diagnosis. These infections occurred during the early stage of care (median [IQR] time, 13 [8–19] days after diagnosis) with mainly pulmonary (45%), catheter-associated bacteremia (22%) and urinary tract (21%) infections. In multivariable analysis, positive ANCA (HR [95% CI] 1.62 [1.07−2.44]; p = 0.02) and age at diagnosis (HR [95% CI] 1.10 [1.00–1.21]; p = 0.047) remained independently associated with SI. Age-adjusted severe infection during the first three months was associated with an increased three-year mortality rate (HR [95% CI] 3.13 [1.24–7.88]; p = 0.01). Thus, SI is a common early complication in anti-GBM disease, particularly in the elderly and those with positive anti-neutrophil cytoplasmic antibodies (ANCA). No significant association was observed between immunosuppressive strategy and occurrence of SI.

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Section: Discussionmentioning

confidence: 99%

Severe Infection in Anti-Glomerular Basement Membrane Disease: A Retrospective Multicenter French Study

Caillard

Vigneau

Hazzan

et al. 2020

JCM

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“…But severe infections were not rare in this subgroup of patients, and there seemed to be more infections than patients with other renal diseases [16][17][18][19] or rheumatic and musculoskeletal diseases (RMDs) [26] received rituximab administration. In RMDs patients, the event rate was 9.8 per 100 person-years [26], while in Kronbichler's study, severe infections occurred in 25.52% patients and the event rate was 26.06 per 100 person-years in AAV patients receiving rituximab therapy [20]. In general, patients with AAV may have an increased risk of developing severe infections following rituximab therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Age and serum creatinine were found to be associated with severe infection within the first year of follow-up. Since in Kronbichler's study [20], trimethoprim-sulfamethoxazole reduced the risk of severe infections, it was included into multivariable Cox regression model as well.…”

Section: Risk Factors Of Severe Infectionmentioning

confidence: 99%

“…In MAINRITSAN study, severe infections developed in 19% patients in the rituximab group [13]. Recently, Kronbichler A, et al found that severe/life-threatening infections occurred in 25.52% AAV patients receiving rituximab therapy, with an event rate of 26.06 per 100 person-years [20]. These observations revealed that infections were still common in AAV patients receiving this new treatment regimen and should deserve careful attention.…”

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confidence: 95%

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Severe infections following rituximab treatment in antineutrophil cytoplasmic antibody-associated vasculitis

Chen

Zhao

2020

Preprint

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Background: Severe infections were not rare in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patients treated with rituximab. The current study aimed to evaluate severe infections in AAV patients received rituximab administration in a single Chinese center.Methods: Twenty-seven patients were retrospectively included in this study. Their demographic and clinical data were analyzed. Severe infections were classified as grade ≥3 as proposed by the Common Terminology Criteria for Adverse Events V.4.0.Results: Patients were followed up for 23.6±14.0 months from the time of rituximab initiation (mean rituximab dose 1270.4 mg). Ten severe infection events were recorded in 10 (37.0%) patients, corresponding to an event rate of 20.9 per 100 person-years. Pulmonary infections were the leading infectious complications (90%). Eight of the 10 infections occurred during the first 12 months of follow-up. In multivariable analysis, severe infection in the first year was independently associated with age (HR 1.121, 95% CI 1.011 to 1.243, P=0.031) and serum creatinine level (increased by per 88.4 μmol/L, HR 1.493, 95% CI 1.017 to 2.191, P=0.041).Conclusions: In AAV patients receiving rituximab, severe infections were common even with the low-dose regimen. Pulmonary infections were the leading cause, and most infections occurred during the first 12 months of follow-up. Older age and renal dysfunction were the risk factors for infection.

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“…Для сравнения, по данным РКИ RITUXVAS [5] и многоцентрового исследования у больных ЭГПА [14] на фоне лечения РТМ частота серьезных инфекционных НР за 12 мес наблюдения при ГПА и МПА составила 18%, при ЭГПА -15%, частота летальных случаев при ГПА и МПА достигала 18% [5]. В соответствии с недавно опубликованными объединенными результатами двух европейских центров [27], у 192 больных АНЦА-СВ (включая 134 случая ГПА, 28 -МПА и 30 -ЭГПА), получавших лечение РТМ в средней суммарной дозе 4,75 г, частота серьезных инфекционных НР при средней длительности наблюдения 22,6 мес достигала 25,5%, или 26 на 100 пациенто-лет. По данным американского многоцентрового исследования [28], включившего 97 больных ГПА и МПА с продолжительностью наблюдения 4 года, на фоне лечения РТМ (в среднем 8 инфузий) частота серьезных инфекций составила 14% (7,1 на 100 пациенто-лет), частота летальных исходов -9%.…”

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Ten-year experience with rituximab for induction and maintenance therapy in patients with ANCA-associated systemic vasculitis

Бекетова¹,

Насонов

2020

Sovremennaâ revmatologiâ

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Rituximab (RTM), a monoclonal antibody against CD20+ receptors on the membrane of B-cells, is becoming increasingly important for the induction and maintenance treatment of antineutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis (ANCA-SV). The challenge facing us is to optimize its efficacy, while limiting adverse events (AEs).Objective: to evaluate the efficacy and safety of RTM used for the induction and maintenance of remission in ANCA-SV on the basis of 10-year single-center experience.Patients and methods. The paper presents the authors’ own 10-year experience with RTM used for the induction and maintenance of remission in 103 patients with ANCA-SV, including granulomatosis with polyangiitis (GPA) (n=58), microscopic polyangiitis (MPA) (n=35), ANCA-positive eosinophilic granulomatosis with polyangiitis (EGPA) (n=4), and ANCA-negative EGPA (n=6). The duration of a follow-up after initiation of RTM treatment was more than a year (with the exception of death cases) and averaged 25 to 58 months in different ANCA-SV groups. The patients were monitored every 3 months. The intervals between repeated cycles were dependent on the time course of changes in clinical and laboratory parameters. The mean cumulative RTM dose exceeded 3 g; 75% of patients received repeated cycles of RMT usually at a cumulative dose of 0.5–1.0 g at a 4–12-month interval.Results and discussion. Repeated RTM cycles for ANCA-SV were highly effective; the clinical response rate was 97%, while 90–93% of patients with different types of ANCA-SV achieved complete clinical response. Despite the fact that the examined population included a high proportion of patients with a severe or refractory course of the disease; ANCA-SV patients showed 10% mortality rates during the entire follow-up period. Anti-B-cell therapy with RTM is of great importance in obtaining long-term optimal results, making it possible to improve ANCA-SV control and to minimize the cumulative dose of glucocorticoids. Since in ANCA-SV, the use of repeated cycles of RTM, including that at a reduced dose of 0.5 g, contributes to the higher efficiency of treatment and to the lower risk of relapse, it is advisable to perform long-term (≥2 years) RTM therapy, by controlling the parameters of clinical and immunological activities and the levels of circulating CD20+ B cells and serum immunoglobulins, deficiency of which can potentially increase the risk of infectious AEs. When planning RTM therapy, it is necessary to consider the specific features of the safety profile for individual nosological entities and to make a careful appropriate monitoring of ANCA-SV patients receiving RTM. The risk of late-onset neutropenia was highest in patients with all types of ANCA-SV (3–10%). Infections in patients with GPA and MPA constitute a substantial proportion (10–11%) in serious AEs. Management of EGPA patients requires alertness to the risk of infusion-related reactions, primarily bronchospasm.Conclusion. There is a need for further investigation of an anti-B-cell therapy strategy, including the efficacy and safety of RTM in ANCA-SV and for clarification of indications and optimal RTM treatment regimens.

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Trimethoprim–sulfamethoxazole prophylaxis prevents severe/life-threatening infections following rituximab in antineutrophil cytoplasm antibody-associated vasculitis

Cited by 116 publications

References 22 publications

Severe Infection in Anti-Glomerular Basement Membrane Disease: A Retrospective Multicenter French Study

Severe Infection in Anti-Glomerular Basement Membrane Disease: A Retrospective Multicenter French Study

Severe infections following rituximab treatment in antineutrophil cytoplasmic antibody-associated vasculitis

Ten-year experience with rituximab for induction and maintenance therapy in patients with ANCA-associated systemic vasculitis

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