The comparison of isavuconazole and voriconazole as oral sequential therapy for invasive aspergillosis in patients with hematological malignancies
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摘要: 目的 探究并分析比较口服艾沙康唑胶囊与伏立康唑片剂在血液病患者抗真菌口服序贯治疗的疗效及安全性。方法 回顾性分析中国医学科学院血液病医院干细胞移植中心2019年11月至2023年1月诊断为侵袭性曲霉菌病，并应用伏立康唑针剂抗真菌治疗的患者共45例。其中22例患者应用伏立康唑片口服序贯治疗，23例患者应用艾沙康唑胶囊口服序贯治疗。结果 艾沙康唑组中仅1例患者评价治疗无效，其余22例治疗有反应的患者中17例评估为完全缓解，治疗缓解率为95.65%(22/23)，完全缓解率为73.91%(17/23)。伏立康唑治组的治疗缓解率为86.36%(19/22)，完全缓解率为50.00%(11/22)。2组患者在治疗缓解率上差异无统计学意义，且2组患者服药期间耐受性良好。结论 应用伏立康唑针剂静脉抗真菌治疗后应用艾沙康唑胶囊口服序贯与伏立康唑片口服序贯治疗相比疗效相当，且安全性良好。Abstract: Objective To investigate and analyze the efficacy and safety of oral isavuconazole and voriconazole as oral sequential therapy for invasive aspergillosis in patients with hematological diseases.Methods The clinical data of 45 patients diagnosed as invasive aspergillosis and treated with voriconazole intravenously in the stem cell transplantation center of Hematology Hospital of Chinese Academy of Medical Sciences from November 2019 to January 2023 were retrospectively analyzed. Among them, 22 patients were treated with oral sequential therapy of voriconazole tablets and 23 patients were treated with oral sequential therapy of isavuconazole capsules.Results Only 1 patient in the isavuconazole group was evaluated as ineffective, and 17 of the remaining 22 patients who responded to treatment were evaluated as complete remission. The overall remission rate was 95.65%(22/23), and the complete remission rate was 73.91%(17/23). The overall remission rate of voriconazole treatment group was 86.36%(19/22), and the complete remission rate was 50.00%(11/22). There was no significant difference in the remission rate between the two groups. Additionally, patients in both groups were well tolerated.Conclusion Isavuconazole has similar efficacy and good safety as oral sequential therapy compared to voriconazole tablets for invasive aspergillosis in patients with hematological diseases.
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表 1 2组患者临床基线资料比较
例(%) 临床资料 艾沙康唑组(23例) 伏立康唑组(22例) P 年龄/岁 42.09±13.93 40.27±10.64 0.627 性别 1.000 男 15(65.22) 14(63.64) 女 8(34.78) 8(36.36) 原发病 0.102 急性髓系白血病 15(65.22) 11(50.00) 急性淋巴细胞白血病 5(21.74) 2(9.09) 骨髓增生异常综合征/骨髓增殖性肿瘤 3(13.04) 9(40.91) 原发病治疗阶段 0.038 化疗 16(69.57) 8(36.36) 化疗后桥接移植 10/16 6/8 造血干细胞移植后 7(30.43) 14(63.64) 处于粒细胞缺乏状态 5(21.74) 4(18.18) 1.000 评估的侵袭性曲霉菌病诊断类型 0.450 未确定 5(21.74) 6(27.27) 拟诊或临床诊断 14(60.87) 15(68.18) 确诊 4(17.39) 1(4.55) 感染部位 0.187 肺 22(95.65) 18(81.82) 鼻窦等其他部位 1(4.35) 4(18.18) 
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表 2 2组患者抗感染疗效比较
例(%) 不同治疗阶段疗效 艾沙康唑组(23例) 伏立康唑组(22例) P 化疗患者疗效评估 例数 16 8 0.069 完全缓解 14(87.50) 4(50.00) 部分缓解 2(12.50) 4(50.00) 无效或进展 0 0 移植后患者疗效评估 例数 7 14 0.848 完全缓解 3(42.86) 7(50.00) 部分缓解 3(42.86) 4(28.57) 无效或进展 1(14.29) 3(21.43) 总体疗效评估 例数 23 22 0.228 完全缓解 17(73.91) 11(50.00) 部分缓解 5(21.74) 8(36.36) 无效或进展 1(4.35) 3(13.64) 总体100 d内全因死亡率 1(4.35) 3(13.64) 0.346
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[1] Kontoyiannis DP, Marr KA, Park BJ, et al. Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001-2006: overview of the Transplant-Associated Infection Surveillance Network(TRANSNET)Database[J]. Clin Infect Dis, 2010, 50(8): 1091-1100. doi: 10.1086/651263
[2] Gong Y, Li C, Wang C, Li J, et al. Epidemiology and Mortality-Associated Factors of Invasive Fungal Disease in Elderly Patients: A 20-Year Retrospective Study from Southern China[J]. Infect Drug Resist, 2020, 13: 711-723. doi: 10.2147/IDR.S242187
[3] 中华医学会血液学分会抗感染学组. 艾沙康唑临床应用专家共识(2023版)[J]. 临床血液学杂志, 2023, 36(5): 295-302. doi: 10.13201/j.issn.1004-2806.2023.05.001
[4] Valentine JC, Morrissey CO, Tacey MA, et al. A population-based analysis of attributable hospitalisation costs of invasive fungal diseases in haematological malignancy patients using data linkage of state-wide registry and costing databases: 2009-2015[J]. Mycoses, 2020, 63(2): 162-171. doi: 10.1111/myc.13033
[5] Sun Y, Meng F, Han M, et al. Epidemiology, management, and outcome of invasive fungal disease in patients undergoing hematopoietic stem cell transplantation in China: a multicenter prospective observational study[J]. Biol Blood Marrow Transplant, 2015, 21(6): 1117-1126. doi: 10.1016/j.bbmt.2015.03.018
[6] Schelenz S, Barnes RA, Barton RC, et al. British Society for Medical Mycology best practice recommendations for the diagnosis of serious fungal diseases[J]. Lancet Infect Dis, 2015, 15(4): 461-474. doi: 10.1016/S1473-3099(15)70006-X
[7] Patterson TF, Thompson GR 3rd, Denning DW, et al. Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America[J]. Clin Infect Dis, 2016, 63(4): e1-e60. doi: 10.1093/cid/ciw326
[8] Limper AH, Knox KS, Sarosi GA, et al. An official American Thoracic Society statement: Treatment of fungal infections in adult pulmonary and critical care patients[J]. Am J Respir Crit Care Med, 2011, 183(1): 96-128. doi: 10.1164/rccm.2008-740ST
[9] Ananda-Rajah MR, Kontoyiannis D. Isavuconazole: a new extended spectrum triazole for invasive mold diseases[J]. Future Microbiol, 2015, 10(5): 693-708. doi: 10.2217/fmb.15.34
[10] Shirley M, Scott LJ. Isavuconazole: A Review in Invasive Aspergillosis and Mucormycosis[J]. Drugs, 2016, 76(17): 1647-1657. doi: 10.1007/s40265-016-0652-6
[11] Zurl C, Waller M, Schwameis F, et al. Isavuconazole Treatment in a Mixed Patient Cohort with Invasive Fungal Infections: Outcome, Tolerability and Clinical Implications of Isavuconazole Plasma Concentrations[J]. J Fungi(Basel), 2020, 6(2): 90.
[12] Jenks JD, Mehta SR, Hoenigl M. Broad spectrum triazoles for invasive mould infections in adults: Which drug and when?[J]. Med Mycol, 2019, 57(Supplement_2): S168-S178. doi: 10.1093/mmy/myy052
[13] Tissot F, Agrawal S, Pagano L, et al. ECIL-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients[J]. Haematologica, 2017, 102(3): 433-444. doi: 10.3324/haematol.2016.152900
[14] Ullmann AJ, Aguado JM, Arikan-Akdagli S, et al. Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline[J]. Clin Microbiol Infect, 2018, 24 Suppl 1: e1-e38.
[15] Kronig I, Masouridi-Levrat S, Chalandon Y, et al. Clinical Considerations of Isavuconazole Administration in High-Risk Hematological Patients: A Single-Center 5-Year Experience[J]. Mycopathologia, 2021, 186(6): 775-788. doi: 10.1007/s11046-021-00583-9
[16] Monforte A, Los-Arcos I, Martín-Gómez MT, et al. Safety and Effectiveness of Isavuconazole Treatment for Fungal Infections in Solid Organ Transplant Recipients(ISASOT Study)[J]. Microbiol Spectr, 2022, 10(1): e0178421. doi: 10.1128/spectrum.01784-21
[17] Maertens JA, Raad, II, Marr KA, et al. Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi(SECURE): a phase 3, randomised-controlled, non-inferiority trial[J]. Lancet, 2016, 387(10020): 760-769. doi: 10.1016/S0140-6736(15)01159-9
[18] Van Matre ET, Evans SL, Mueller SW, et al. Comparative evaluation of isavuconazonium sulfate, voriconazole, and posaconazole for the management of invasive fungal infections in an academic medical center[J]. Ann Clin Microbiol Antimicrob, 2019, 18(1): 13. doi: 10.1186/s12941-019-0311-3
[19] Dagher H, Hachem R, Chaftari AM, et al. Real-World Use of Isavuconazole as Primary Therapy for Invasive Fungal Infections in High-Risk Patients with Hematologic Malignancy or Stem Cell Transplant[J]. J Fungi(Basel), 2022, 8(1): 1-16.
[20] Riccardi N, Alagna R, Saderi L, et al. Towards tailored regimens in the treatment of drug-resistant tuberculosis: a retrospective study in two Italian reference Centres[J]. BMC Infect Dis, 2019, 19(1): 564. doi: 10.1186/s12879-019-4211-0
[21] Scabini S, Lupia T, Angilletta R, et al. Real-life use of isavuconazole outside the hematological wards[J]. Eur J Intern Med, 2019, 70: e10-e12. doi: 10.1016/j.ejim.2019.09.005
[22] Hassouna H, Athans V, Brizendine KD. Real-world use-Isavuconazole at a large academic medical center[J]. Mycoses, 2019, 62(6): 534-541. doi: 10.1111/myc.12910
[23] Ordaya EE, Alangaden GJ. Real-Life Use of Isavuconazole in Patients Intolerant to Other Azoles[J]. Clin Infect Dis, 2016, 63(11): 1529-1530. doi: 10.1093/cid/ciw585
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