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变应性支气管肺曲霉病患者使用生物制剂的疗效:系统评价和荟萃分析。

Efficacy of Biologics in Patients with Allergic Bronchopulmonary Aspergillosis: A Systematic Review and Meta-Analysis.

机构信息

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Department of Allergy and Clinical Immunology, Joint International Research Laboratory of Respiratory Health, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China.

Department of Respiratory and Critical Care Medicine, People's Hospital of Yangjiang, Yangjiang, Guangdong, China.

出版信息

Lung. 2024 Aug;202(4):367-383. doi: 10.1007/s00408-024-00717-y. Epub 2024 Jun 19.

Abstract

BACKGROUND

Treatment of allergic bronchopulmonary aspergillosis (ABPA) is challenging. Biological therapies have been reported as adjunctive treatments for ABPA, primarily in case series or case reports. This study aimed to analyze the efficacy of biologics for managing ABPA both qualitatively and quantitatively.

METHODS

All articles on APBA published in October 2023 were searched in PubMed, Web of Science, ClinicalTrials.gov, and Embase databases. The effects of interest were the mean changes from baseline for outcomes, including exacerbation rates, oral corticosteroids usage (OCS), and total immunoglobulin E (IgE) levels. Reported outcomes were quantitatively synthesized by usual or individual patient data (IPD) meta-analyses. PROSPERO registration number: CRD42022373396.

RESULTS

A total of 86 studies were included in the systematic review including 346 patients. Sixteen studies on omalizumab were pooled for the usual meta-analysis. Omalizumab therapy significantly reduced exacerbation rates (- 2.29 [95%CI - 3.32, - 1.26]), OCS dosage (- 10.91 mg [95%CI - 18.98, - 2.85]), and total IgE levels (- 273.07 IU/mL [95%CI - 379.30, - 166.84]), meanwhile improving FEV1% predicted (10.09% [95%CI 6.62, 13.55]). Thirty-one studies on dupilumab, mepolizumab, or benralizumab were pooled to perform an IPD meta-analysis, retrospectively. Both dupilumab and mepolizumab significantly reduced exacerbation rates, OCS, and total IgE levels. Benralizumab showed a similar trend, but it was not statistically significant. Tezepelumab showed weak evidence of its effects on ABPA. All five biologics led to milder clinical symptoms (e.g., cough, wheezing) with serious adverse effects that happened once in omalizumab treatment.

CONCLUSION

These results indicate the clinical benefit of omalizumab, dupilumab, and mepolizumab in patients with ABPA. Further randomized, controlled studies with a larger sample size and longer follow-up are needed to confirm these findings.

摘要

背景

过敏性支气管肺曲霉病(ABPA)的治疗具有挑战性。生物疗法已被报道为 ABPA 的辅助治疗方法,主要是在病例系列或病例报告中。本研究旨在定性和定量分析生物制剂治疗 ABPA 的疗效。

方法

检索 2023 年 10 月在 PubMed、Web of Science、ClinicalTrials.gov 和 Embase 数据库中发表的所有关于 APBA 的文章。感兴趣的效果是结局的基线变化均值,包括加重率、口服皮质类固醇(OCS)的使用和总免疫球蛋白 E(IgE)水平。通过常规或个体患者数据(IPD)荟萃分析对报告的结局进行定量综合。PROSPERO 注册号:CRD42022373396。

结果

系统评价共纳入 86 项研究,包括 346 名患者。对奥马珠单抗的 16 项研究进行了常规荟萃分析。奥马珠单抗治疗可显著降低加重率(-2.29[95%CI-3.32,-1.26])、OCS 剂量(-10.91mg[95%CI-18.98,-2.85])和总 IgE 水平(-273.07IU/mL[95%CI-379.30,-166.84]),同时改善 FEV1%预测值(10.09%[95%CI 6.62,13.55])。对 31 项关于度普利尤单抗、美泊利单抗或贝那利珠单抗的研究进行了 IPD 荟萃分析,采用回顾性研究设计。度普利尤单抗和美泊利单抗均可显著降低加重率、OCS 和总 IgE 水平。贝那利珠单抗也显示出类似的趋势,但无统计学意义。特泽普单抗对 ABPA 的疗效显示出较弱的证据。五种生物制剂均可减轻咳嗽、喘息等临床症状,且严重不良事件仅在奥马珠单抗治疗中发生一次。

结论

这些结果表明奥马珠单抗、度普利尤单抗和美泊利单抗对 ABPA 患者具有临床获益。需要进一步开展随机、对照研究,以更大的样本量和更长的随访时间来证实这些发现。

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