London Centre for Neglected Tropical Disease Research and MRC Centre for Global Infectious Disease Analysis (MRC GIDA), Department of Infectious Disease Epidemiology, Imperial College London , London, UK.
London Centre for Neglected Tropical Disease Research, Department of Pathobiology and Population Sciences, Royal Veterinary College , Hatfield, UK.
Expert Rev Anti Infect Ther. 2020 Nov;18(11):1067-1081. doi: 10.1080/14787210.2020.1792772. Epub 2020 Jul 26.
Moxidectin is a milbemycin endectocide recently approved for the treatment of human onchocerciasis. Onchocerciasis, earmarked for elimination of transmission, is a filarial infection endemic in Africa, Yemen, and the Amazonian focus straddling Venezuela and Brazil. Concerns over whether the predominant treatment strategy (yearly mass drug administration (MDA) of ivermectin) is sufficient to achieve elimination in all endemic foci have refocussed attention upon alternative treatments. Moxidectin's stronger and longer microfilarial suppression compared to ivermectin in both phase II and III clinical trials indicates its potential as a novel powerful drug for onchocerciasis elimination.
This work summarizes the chemistry and pharmacology of moxidectin, reviews the phase II and III clinical trials evidence on tolerability, safety, and efficacy of moxidectin versus ivermectin, and discusses the implications of moxidectin's current regulatory status.
Moxidectin's superior clinical performance has the potential to substantially reduce times to elimination compared to ivermectin. If donated, moxidectin could mitigate the additional programmatic costs of biannual ivermectin distribution because, unlike other alternatives, it can use the existing community-directed treatment infrastructure. A pediatric indication (for children <12 years) and determination of its usefulness in onchocerciasis-loiasis co-endemic areas will greatly help fulfill the potential of moxidectin for the treatment and elimination of onchocerciasis.
莫昔克丁是一种米尔贝肟类驱虫药,最近被批准用于治疗人类盘尾丝虫病。盘尾丝虫病是一种正在被消除传播的丝虫病,在非洲、也门以及横跨委内瑞拉和巴西的亚马逊流域流行。由于担心主要的治疗策略(每年一次的伊维菌素大规模药物治疗(MDA))是否足以在所有流行地区实现消除,人们重新关注替代治疗方法。莫昔克丁在 II 期和 III 期临床试验中比伊维菌素具有更强和更长时间的微丝蚴抑制作用,这表明它有可能成为消除盘尾丝虫病的一种新型强力药物。
这项工作总结了莫昔克丁的化学和药理学,回顾了 II 期和 III 期临床试验中关于莫昔克丁与伊维菌素的耐受性、安全性和疗效的证据,并讨论了莫昔克丁目前监管状况的影响。
莫昔克丁的卓越临床疗效有潜力比伊维菌素大大缩短消除时间。如果捐赠,莫昔克丁可以减轻每年两次伊维菌素分发的额外计划成本,因为与其他替代品不同,它可以利用现有的社区定向治疗基础设施。儿科适应症(用于<12 岁儿童)和确定其在盘尾丝虫病-罗阿丝虫病共流行地区的有用性将极大地帮助实现莫昔克丁治疗和消除盘尾丝虫病的潜力。