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三苯甲基磺胺甲恶唑预防抗中性粒细胞胞质抗体相关性血管炎患者在接受利妥昔单抗治疗后发生严重/危及生命的感染。

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

机构信息

Vasculitis and Lupus Clinic, Addenbrooke's Hospital, Cambridge, UK.

Department of Internal Medicine IV (Nephrology and Hypertension), Anichstraße, Innsbruck, Austria.

出版信息

Ann Rheum Dis. 2018 Oct;77(10):1440-1447. doi: 10.1136/annrheumdis-2017-212861. Epub 2018 Jun 27.

Abstract

OBJECTIVE

We aimed to assess risk factors for the development of severe infection in patients with antineutrophil cytoplasm antibody-associated vasculitis (AAV) receiving rituximab.

METHODS

192 patients with AAV were identified. Univariate and multivariate analyses were performed to identify risk factors for severe infection following rituximab. Severe infections were classified as grade ≥3 as proposed by the Common Terminology Criteria for Adverse Events V.4.0.

RESULTS

95 severe infections were recorded in 49 (25.52%) patients, corresponding to an event rate of 26.06 per 100 person-years. The prophylactic use of trimethoprim-sulfamethoxazole was associated with a lower frequency of severe infections (HR 0.30, 95% CI 0.13 to 0.69), while older age (HR 1.03, 95% CI 1.01 to 1.05), endobronchial involvement (HR 2.21, 95% CI 1.14 to 4.26), presence of chronic obstructive pulmonary disease (HR 6.30, 95% CI 1.08 to 36.75) and previous alemtuzumab use (HR 3.97, 95% CI 1.50 to 10.54) increased the risk. When analysis was restricted to respiratory tract infections (66.3% of all infections), endobronchial involvement (HR 4.27, 95% CI 1.81 to 10.06), severe bronchiectasis (HR 6.14, 95% CI 1.18 to 31.91), higher neutrophil count (HR 1.19, 95% CI 1.06 to 1.33) and major relapse (HR 3.07, 95% CI 1.30 to 7.23) as indication for rituximab use conferred a higher risk, while refractory disease (HR 0.25, 95% CI 0.07 to 0.90) as indication had a lower frequency of severe infections.

CONCLUSIONS

We found severe infections in one quarter of patients with AAV receiving rituximab. Trimethoprim-sulfamethoxazole prophylaxis reduced the risk, while especially bronchiectasis and endobronchial involvement are risk factors for severe respiratory infections.

摘要

目的

评估接受利妥昔单抗治疗的抗中性粒细胞胞浆抗体相关性血管炎(AAV)患者发生严重感染的危险因素。

方法

共纳入 192 例 AAV 患者。采用单因素和多因素分析确定利妥昔单抗治疗后发生严重感染的危险因素。严重感染根据常见不良事件术语标准 4.0 版(CTCAE v4.0)分为≥3 级。

结果

49 例(25.52%)患者发生 95 例严重感染,感染发生率为 26.06/100 人年。预防性使用复方磺胺甲噁唑可降低严重感染的发生频率(HR 0.30,95%CI 0.13 至 0.69),而年龄较大(HR 1.03,95%CI 1.01 至 1.05)、支气管内受累(HR 2.21,95%CI 1.14 至 4.26)、慢性阻塞性肺疾病(HR 6.30,95%CI 1.08 至 36.75)和既往使用阿仑单抗(HR 3.97,95%CI 1.50 至 10.54)会增加风险。当分析仅限于呼吸道感染(所有感染的 66.3%)时,支气管内受累(HR 4.27,95%CI 1.81 至 10.06)、严重支气管扩张症(HR 6.14,95%CI 1.18 至 31.91)、较高的中性粒细胞计数(HR 1.19,95%CI 1.06 至 1.33)和主要复发(HR 3.07,95%CI 1.30 至 7.23)作为利妥昔单抗使用的指征会增加风险,而难治性疾病(HR 0.25,95%CI 0.07 至 0.90)作为指征则会降低严重感染的发生率。

结论

我们发现接受利妥昔单抗治疗的 AAV 患者中有四分之一发生严重感染。复方磺胺甲噁唑预防可降低风险,而支气管扩张症和支气管内受累是严重呼吸道感染的危险因素。

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