Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.
Department of Hematology, the First Affiliated Hospital of Soochow University, Suzhou, China.
Mycoses. 2021 Apr;64(4):445-456. doi: 10.1111/myc.13233. Epub 2021 Jan 31.
Isavuconazole is a broad-spectrum triazole for the treatment of invasive fungal disease (IFD).
To investigate the clinical experience with isavuconazole in Chinese individuals.
PATIENTS/METHODS: Participants were Chinese healthy volunteers from a Phase I pharmacokinetics (PK) and safety study of single/multiple doses of isavuconazole (n = 36) and Chinese patients from the global Phase III SECURE study that assessed safety and efficacy of isavuconazole vs voriconazole for IFD treatment (n = 26).
No clinically relevant differences in PK were found between Chinese and Western participants, although exposure was increased in Chinese volunteers. Treatment-emergent adverse events (TEAEs) were reported in 75.0% of healthy volunteers, many of which were infusion-related. No serious AEs were reported. In SECURE, findings in Chinese patients (n = 26) were similar to the global population. For patients who received ≥1 dose of study drug, allcause mortality from first dose to Day 42 was 10.0% (1/10) with isavuconazole and 25.0% (4/16) with voriconazole (treatment difference [95% confidence interval, CI]: -15.0% [-43.2%, 13.2%]). Overall response at the end of treatment for patients with proven/probable IFD was 25.0% and 16.7% with isavuconazole and voriconazole, respectively (treatment difference [95% CI] -8.3% [-60.2%, 43.5%]). Isavuconazole was associated with lower incidence of hepatobiliary, eye, skin, subcutaneous tissue and psychiatric disorders compared with voriconazole and lower incidence of treatment-related TEAEs, serious TEAES or death overall.
Although further research is required, this study demonstrated a favourable risk-benefit profile of isavuconazole in Chinese patients.
伊曲康唑是一种广谱三唑类药物，用于治疗侵袭性真菌感染（IFD）。
研究伊曲康唑在中国人群中的临床应用经验。
患者/方法：本研究纳入了一项伊曲康唑单/多剂量的 I 期药代动力学（PK）和安全性研究的中国健康志愿者（n=36）和全球 III 期 SECURE 研究的中国患者（n=26），评估了伊曲康唑与伏立康唑治疗 IFD 的安全性和疗效。
中国和西方参与者的 PK 无临床相关差异，尽管中国志愿者的暴露量增加。健康志愿者中报告了 75.0%的治疗出现的不良事件（TEAEs），其中许多与输液有关。未报告严重不良事件。在 SECURE 研究中，中国患者（n=26）的研究结果与全球人群相似。对于接受≥1 剂研究药物的患者，从首次给药到第 42 天的全因死亡率，伊曲康唑组为 10.0%（1/10），伏立康唑组为 25.0%（4/16）（治疗差异[95%置信区间，CI]：-15.0%[-43.2%，13.2%]）。有确诊/可能 IFD 的患者在治疗结束时的总体缓解率，伊曲康唑组为 25.0%，伏立康唑组为 16.7%（治疗差异[95%CI]：-8.3%[-60.2%，43.5%]）。与伏立康唑相比，伊曲康唑与较低的肝胆、眼、皮肤、皮下组织和精神障碍发生率相关，且总体治疗相关 TEAEs、严重 TEAEs 或死亡发生率较低。
尽管需要进一步研究，但本研究表明伊曲康唑在中国患者中的风险获益情况良好。
