Barreto Jaison, Sammarco Rosa Patricia, Adams Linda, Aguilar Zuleima, Bakare Nyasha, Chaplan Sandra R, Akli Ruxandra Draghia, Ernault Etienne, Kulke Sarah, Lounis Nacer, Millington Dawn, Palmer James A, Remmerie Bart, Wang Miao, Young Stephanie, Truman Richard, Rebello Paula Frassinetti Bessa
From the Research Division, Instituto Lauro de Souza Lima, Bauru (J.B., P.S.R.), and Fundação de Dermatologia Tropical e Venereologia Alfredo da Matta, Manaus (P.F.B.R.) - both in Brazil; the Department of Health and Human Services, Health Resources and Services Administration, Health Systems Bureau, National Hansen's Disease Program, Laboratory Research Branch, Baton Rouge, LA (L.A., R.T.); Translational Medicine and Early Development Statistics (S.Y.), WAVE Team (Z.A., S.R.C., S.K., D.M., J.A.P., M.W.), Janssen Research and Development, San Diego, CA; Janssen Global Public Health, Janssen Research and Development, Titusville, NJ (N.B., R.D.A.); and Janssen Global Public Health, Janssen Pharmaceutica, Beerse, Belgium (E.E., N.L., B.R.).
N Engl J Med. 2024 Dec 12;391(23):2212-2218. doi: 10.1056/NEJMoa2312928.
Standard multidrug therapy for leprosy may be associated with severe side effects, which add to the stigma and discrimination that affect persons with the disease. In addition, the threat posed by drug-resistant leprosy shows the need for alternative drug combinations and shorter, safer regimens of multidrug therapy.
In this open-label, proof-of-concept study conducted in Brazil, we assigned patients with previously untreated multibacillary leprosy to receive bedaquiline monotherapy for 8 weeks. After completing the 8-week course of bedaquiline, the patients started standard multidrug therapy (as defined by the World Health Organization) for leprosy and were followed for 112 weeks. The primary end point was the change from baseline in the odds of positive growth of in mouse footpads after 8 weeks of bedaquiline therapy. The secondary end point was safety. Exploratory end points included change in the clinical signs and symptoms of leprosy and in the molecular viability of (measured by a quantitative reverse-transcriptase-polymerase-chain-reaction assay).
A total of nine patients were included in the modified intention-to-treat analysis. The odds of positive growth had decreased from 100% in all the patients at baseline to no growth after 4 weeks of bedaquiline monotherapy. After 7 weeks of treatment, all the patients showed improvement in the appearance of skin lesions as compared with baseline. Seven patients had at least one adverse event (all grade 1 or 2) during treatment.
In patients with multibacillary leprosy, bedaquiline monotherapy cleared by 4 weeks of treatment and led to improvement in the appearance of skin lesions by 7 weeks. (Funded by Janssen Research and Development; ClinicalTrials.gov number, NCT03384641.).
麻风病的标准多药疗法可能会伴有严重的副作用，这加剧了影响该疾病患者的耻辱感和歧视。此外，耐药性麻风病带来的威胁表明需要替代药物组合以及更短、更安全的多药治疗方案。
在巴西进行的这项开放标签的概念验证研究中，我们将先前未经治疗的多菌型麻风病患者分配接受8周的贝达喹啉单药治疗。在完成8周的贝达喹啉疗程后，患者开始接受世界卫生组织定义的麻风病标准多药治疗，并随访112周。主要终点是贝达喹啉治疗8周后小鼠足垫中阳性生长几率相对于基线的变化。次要终点是安全性。探索性终点包括麻风病临床体征和症状的变化以及的分子活力变化（通过定量逆转录酶 - 聚合酶链反应测定法测量）。
共有9名患者纳入改良意向性分析。贝达喹啉单药治疗4周后，所有患者小鼠足垫中阳性生长的几率从基线时的100%降至无生长。治疗7周后，与基线相比，所有患者的皮肤病变外观均有改善。7名患者在治疗期间至少发生1次不良事件（均为1级或2级）。
在多菌型麻风病患者中，贝达喹啉单药治疗4周可清除，7周后皮肤病变外观得到改善。（由杨森研发公司资助；ClinicalTrials.gov编号，NCT03384641。）
