背景:血管异常(VAs)越来越多地使用PI3K/AKT/mTOR通路抑制剂治疗。这些药物具有免疫抑制特性,因此理论上使患者过度感染机会性感染,特别是肺孢子虫肺炎(PJP)。PJP预防使用缺乏共识。我们旨在调查接受mTOR/PI3K/AKT抑制剂治疗VAs的患者中PJP的患病率,并确定该人群中预防肺囊虫的适应症。
方法:该研究分为两个部分:(1)我们向VAs的国际专家小组发送了一项调查,询问他们使用肺孢子虫预防药物的情况;(2)我们对所有已发表的接受这些药物治疗VA的患者的文献进行了系统回顾,以估计该人群中PJP的患病率。
结果:分析了来自68位专家的答案:21位(30.9%)回答说,他们在处方mTOR抑制剂时总是添加PJP预防,20例(29.4%),和27(39.7%)从未。对于系统审查,在筛选的3053份报告中,包括217名患者,涉及1189名患者(1143名患者接受了西罗莫司,38依维莫司,4alpelisib,4miransertib)。在1189起案件中,2(0.2%)PJP被报道:一个在西罗莫司和一个在依维莫司。因此,在西罗莫司治疗下,PJP的患病率估计为0.88例/1,000例(95%CI:-0.84~2.59),在依维莫司治疗下,PJP的患病率估计为26.31例/1,000例(95%CI:-24.58~77.18).PJP患者从未接受过预防药物。我们没有发现alpelisib和miransertib下的PJP病例。在218例(18.3%)病例中进行了PJP预防,更常见的儿童(91.3vs.非预防组77.2%,p=0.012),主要是甲氧苄啶-磺胺甲恶唑(186名患者,85.3%)。
结论:我们的研究表明,即使PJP是罕见事件,它可能发生在接受mTOR抑制剂治疗的VAs患者中。虽然我们的结果不能允许修改指导方针,TMP-SMX预防可能适用于有PJP危险因素的患者亚组.
BACKGROUND: Vascular anomalies (VAs) are increasingly being treated with PI3K/AKT/mTOR pathway inhibitors. These drugs have immunosuppressive properties and thus theoretically overexpose patients to opportunistic infections, especially Pneumocystis jirovecii pneumonia (PJP). PJP prophylaxis use lacks consensus. We aimed to investigate the prevalence of PJP in patients receiving mTOR/PI3K/AKT inhibitors for VAs and determine any indication for pneumocystis prophylaxis in this population.
METHODS: The study was conducted in 2 parts: (1) we sent a survey to a panel of international experts of VAs asking about their use of pneumocystis prophylaxis drugs and (2) we performed a systematic
review of the literature of all published cases of patients receiving these drugs for VA to estimate the prevalence of PJP in this population.
RESULTS: Answers from 68 experts were analyzed: 21 (30.9%) answered they always add PJP prophylaxis when prescribing mTOR inhibitors, 20 (29.4%) case-by-case, and 27 (39.7%) never. For the systematic
review, among 3,053 reports screened, 217 were included involving 1,189 patients (1,143 received sirolimus, 38 everolimus, 4 alpelisib, 4 miransertib). Among the 1,189 cases, 2 (0.2%) PJP were reported: one under sirolimus and one under everolimus. Thus, the prevalence of PJP was estimated at 0.88 cases/1,000 patients under sirolimus (95% CI: -0.84 to 2.59) and 26.31 cases/1,000 under everolimus (95% CI: -24.58 to 77.18). Patients with PJP never received prophylaxis drugs. We found no PJP cases under alpelisib and miransertib. PJP prophylaxis was given in 218 (18.3%) cases, more frequently for children (91.3 vs. 77.2% in the non-prophylaxis group, p = 0.012), mostly trimethoprim-sulfamethoxazole (186 patients, 85.3%).
CONCLUSIONS: Our study shows that even if PJP is a rare event, it may occur in patients with VAs treated with an mTOR inhibitor. Although our results cannot allow for revising guidelines, prophylaxis with TMP-SMX might be appropriate for a subgroup of patients with risk factors for PJP.