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生物制剂时代抗中性粒细胞胞浆抗体相关性血管炎的严重感染:来自162例患者的多中心队列的真实数据。

Serious infections in ANCA-associated vasculitides in the biologic era: real-life data from a multicenter cohort of 162 patients.

作者信息

Thomas Konstantinos, Argyriou Evangelia, Kapsala Noemin, Panagiotopoulos Alexandros, Chalkia Aglaia, Hadziyannis Emilia, Boki Kyriaki, Katsimbri Pelagia, Boumpas Dimitrios T, Giannou Panagiota, Petras Dimitrios, Vassilopoulos Dimitrios

机构信息

Joint Rheumatology Program, Clinical Immunology-Rheumatology Unit, 2nd Department of Medicine and Laboratory, National and Kapodistrian University of Athens School of Medicine, Hippokration General Hospital, 114 Vass. Sophias Ave, 115 27, Athens, Greece.

Rheumatology Unit, Sismanoglio General Hospital, Athens, Greece.

出版信息

Arthritis Res Ther. 2021 Mar 20;23(1):90. doi: 10.1186/s13075-021-02452-8.

Abstract

BACKGROUND

Serious infections (SI) are common in patients with ANCA-associated vasculitides (AAV) like granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Real-life data regarding their incidence and predisposing factors-after the introduction of B cell depleting agents-are limited while data quantifying the risk per treatment modality and year of the disease are missing. Here, we aim to describe in details the incidence and the risk factors for SI in a contemporary AAV cohort.

METHODS

Multicenter, observational, retrospective study of AAV patients followed in three tertiary referral centers.

RESULTS

We included 162 patients with GPA (63%) and MPA (37%), males 51.9%, mean age 60.9 years, ΑΝCA+ 86%, and generalized disease 80%. During follow-up (891.2 patient-years, mean 5.4 years), 67 SI were recorded in 50 patients at an incidence rate of 7.5 per 100 patient-years. The SI incidence rate was higher during induction with cyclophosphamide (CYC) compared to rituximab (RTX, 19.3 vs. 11.3 per 100 patient-years, respectively) while it was lower and comparable between RTX and other regimens (5.52 vs. 4.54 per 100 patient-years, respectively) in the maintenance phase. By multivariate analysis, plasmapheresis (PLEX) and/or dialysis was a strong predictor for an SI during the 1st year after diagnosis (OR = 3.16, 95% CI 1.001-9.96) and throughout the follow-up period (OR = 5.21, 95% CI 1.93-14.07). In contrast, a higher baseline BVAS (OR = 1.11, 95% CI 1.01-1.21) was associated with SI only during the 1st year.

CONCLUSIONS

In this real-life study of patients with AAV, the SI incidence was higher during CYC compared to RTX induction while there was no difference between RTX and other agents used for maintenance therapy. Higher disease activity at baseline and need for PLEX and/or dialysis were independent factors associated with an SI.

摘要

背景

严重感染(SI)在抗中性粒细胞胞浆抗体相关性血管炎(AAV)患者中很常见,如肉芽肿性多血管炎(GPA)和显微镜下多血管炎(MPA)。在引入B细胞耗竭剂后,关于其发病率和易感因素的实际数据有限,而量化每种治疗方式和疾病年份风险的数据缺失。在此,我们旨在详细描述当代AAV队列中SI的发病率和危险因素。

方法

对在三个三级转诊中心随访的AAV患者进行多中心、观察性、回顾性研究。

结果

我们纳入了162例GPA患者(63%)和MPA患者(37%),男性占51.9%,平均年龄60.9岁,抗中性粒细胞胞浆抗体阳性者占86%,全身性疾病患者占80%。在随访期间(891.2患者年,平均5.4年),50例患者记录到67次SI,发病率为每100患者年7.5次。与利妥昔单抗(RTX)相比,环磷酰胺(CYC)诱导期间的SI发病率更高(分别为每100患者年19.3次和11.3次),而在维持期,RTX与其他方案之间的发病率较低且相当(分别为每100患者年5.52次和4.54次)。多变量分析显示,血浆置换(PLEX)和/或透析是诊断后第1年(OR = 3.16,95%CI 1.001 - 9.96)及整个随访期(OR = 5.21,95%CI 1.93 - 14.07)发生SI的有力预测因素。相比之下,仅在第1年,较高的基线BVAS(OR = 1.11,95%CI 1.01 - 1.21)与SI相关。

结论

在这项AAV患者的实际研究中,CYC诱导期间的SI发病率高于RTX,而RTX与用于维持治疗的其他药物之间无差异。基线疾病活动度较高以及需要PLEX和/或透析是与SI相关的独立因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9157/7980356/695b016974e5/13075_2021_2452_Fig1_HTML.jpg

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