Department of Internal and Vascular Medicine, National Referral Centre for Rare Juvenile Rheumatological and Autoimmune Diseases (RAISE), Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France; Faculty of Medicine, Université de Lyon, Université Lyon 1, France; Lyon Immunopathology Federation (LIFE), University of Lyon, Hospices Civils de Lyon, France.
Department of Internal and Vascular Medicine, National Referral Centre for Rare Juvenile Rheumatological and Autoimmune Diseases (RAISE), Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France; Faculty of Medicine, Université de Lyon, Université Lyon 1, France; Lyon Immunopathology Federation (LIFE), University of Lyon, Hospices Civils de Lyon, France; Université de Lyon, Université Lyon 1, CNRS, Laboratoire de Biométrie et Biologie Evolutive UMR 5558, F-69622 Villeurbanne, France.
Autoimmun Rev. 2020 May;19(5):102505. doi: 10.1016/j.autrev.2020.102505. Epub 2020 Mar 12.
The efficacy of rituximab (RTX) for remission induction and maintenance in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) is now established, but the safety, particularly concerning severe infection risk, is not well known.
The purpose of this meta-analysis is to assess the prevalence and incidence of severe infections and the factors explaining heterogeneity in AAV patients treated with RTX.
PubMed and Embase were searched up to December 2017. Prevalence and incidence was pooled using a random-effects model in case of significant heterogeneity (I > 50%). Severe infection was defined as severe when it led to hospitalization, intravenous antibiotics therapy, and/or death. The heterogeneity was explored by subgroup analyses and meta-regression.
The included studies encompassed 1434 patients with a median age of 51.9 years. The overall prevalence and incidence of severe infections was 15.4% (95% CI [8.9; 23.3], I = 90%, 33 studies) and 6.5 per 100 person-years (PY) (95% CI [2.9; 11.4], I = 76%, 18 studies), respectively. The most common infections were bacterial (9.4%, 95% CI [5.1; 14.8]). The prevalence of opportunistic infection was 1.5% (95% CI [0.5; 3.1], I = 58%) including pneumocytis jirovecii infections (0.2%, 95% CI [0.0; 0.6], I = 0), irrespective of prophylaxis administration. Mortality related to infection was estimated at 0.7% (95% CI [0.2; 1.2], I = 27%). The RTX cumulative dose was positively associated with prevalence of infections (13 studies, prevalence increase of 4% per 100 mg, p < .0001). The incidence of infection was negatively associated with duration of follow-up (8 studies, incidence decrease of 9% per year, p = .03).
Prevalence and incidence of severe infections, mainly bacterial ones, were high in AAV patients treated with RTX. This meta-analysis highlights the need for prospective studies to stratify infectious risk and validate cumulative RTX dose and duration of follow-up as modifying factors.
利妥昔单抗（RTX）在抗中性粒细胞胞浆抗体（ANCA）相关性血管炎（AAV）患者中的缓解诱导和维持作用已得到证实，但安全性，特别是严重感染风险，尚不清楚。
本荟萃分析旨在评估在接受 RTX 治疗的 AAV 患者中严重感染的发生率和流行率，并探讨解释异质性的因素。
检索 PubMed 和 Embase 数据库，截至 2017 年 12 月。如果存在显著异质性（I>50%），则使用随机效应模型对流行率和发生率进行汇总。严重感染定义为导致住院、静脉用抗生素治疗和/或死亡的严重感染。通过亚组分析和荟萃回归探索异质性。
纳入的研究共纳入 1434 例中位年龄为 51.9 岁的患者。严重感染的总发生率和发病率分别为 15.4%（95% CI [8.9; 23.3]，I=90%，33 项研究）和 6.5 人年每 100 人（95% CI [2.9; 11.4]，I=76%，18 项研究）。最常见的感染是细菌感染（9.4%，95% CI [5.1; 14.8]）。机会性感染的发生率为 1.5%（95% CI [0.5; 3.1]，I=58%），包括耶氏肺孢子菌感染（0.2%，95% CI [0.0; 0.6]，I=0%），无论是否进行预防治疗。感染相关死亡率估计为 0.7%（95% CI [0.2; 1.2]，I=27%）。RTX 累积剂量与感染发生率呈正相关（13 项研究，每 100mg 增加 4%，p<0.0001）。感染发生率与随访时间呈负相关（8 项研究，每年降低 9%，p=0.03）。
在接受 RTX 治疗的 AAV 患者中，严重感染（主要是细菌感染）的发生率和发病率均较高。本荟萃分析强调需要前瞻性研究来分层感染风险，并验证 RTX 累积剂量和随访时间作为调节因素。
