Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
Clin Infect Dis. 2012 Aug;55(4):543-50. doi: 10.1093/cid/cis474. Epub 2012 May 9.
Miltefosine is the only oral drug available for treatment of Indian visceral leishmaniasis (VL), which was shown to have an efficacy of 94% in a phase III trial in the Indian subcontinent. Its unrestricted use has raised concern about its continued effectiveness. This study evaluates the efficacy and safety of miltefosine for the treatment of VL after a decade of use in India.
An open-label, noncomparative study was performed in which 567 patients received oral miltefosine (50 mg for patients weighing <25 kg, 100 mg in divided doses for those weighing ≥25 kg, and 2.5 mg per kg for those aged <12 years, daily for 28 days) in a directly observed manner. Patients were followed up for 6 months to see the response to therapy.
At the end of treatment the initial cure rate was 97.5% (intention to treat), and 6 months after the end of treatment the final cure rate was 90.3%. The overall death rate was 0.9% (5 of 567), and 2 deaths were related to drug toxicity. Gastrointestinal intolerance was frequent (64.5%). The drug was interrupted in 9 patients (1.5%) because of drug-associated adverse events.
As compared to the phase III trial that led to registration of the drug a decade ago, there is a substantial increase in the failure rate of oral miltefosine for treatment of VL in India.
米替福新是唯一可用于治疗印度内脏利什曼病(VL)的口服药物,在印度次大陆进行的 III 期试验显示其疗效为 94%。其无限制的使用引起了人们对其持续有效性的关注。本研究评估了米替福新在印度使用十年后治疗 VL 的疗效和安全性。
进行了一项开放标签、非对照研究,567 例患者接受了口服米替福新(体重<25kg 的患者给予 50mg,体重≥25kg 的患者给予 100mg 分剂量,年龄<12 岁的患者给予 2.5mg/kg,每日一次,共 28 天),并进行直接观察。患者随访 6 个月以观察治疗反应。
治疗结束时初始治愈率为 97.5%(意向治疗),治疗结束后 6 个月的最终治愈率为 90.3%。总死亡率为 0.9%(5/567),2 例死亡与药物毒性有关。胃肠道不耐受很常见(64.5%)。因药物相关不良事件,有 9 例(1.5%)中断了药物治疗。
与十年前导致药物注册的 III 期试验相比,印度口服米替福新治疗 VL 的失败率显著增加。