Jaison Barreto, Patricia Sammarco Rosa, Linda Adams, Zuleima Aguilar, Nyasha Bakare, Sandra R Chaplan, Ruxandra Draghia Akli, Etienne Ernault, Sarah Kulke, Nacer Lounis, Dawn Millington, James A Palmer, Bart Remmerie, Miao Wang, Stephanie Young, Richard Truman, Paula Frassinetti Bessa Rebello
{"title":"Bedaquiline Monotherapy for Multibacillary Leprosy.","authors":"Jaison Barreto, Patricia Sammarco Rosa, Linda Adams, Zuleima Aguilar, Nyasha Bakare, Sandra R Chaplan, Ruxandra Draghia Akli, Etienne Ernault, Sarah Kulke, Nacer Lounis, Dawn Millington, James A Palmer, Bart Remmerie, Miao Wang, Stephanie Young, Richard Truman, Paula Frassinetti Bessa Rebello","doi":"10.1056/NEJMoa2312928","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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 <i>Mycobacterium leprae</i> 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 <i>M. leprae</i> (measured by a quantitative reverse-transcriptase-polymerase-chain-reaction assay).</p><p><strong>Results: </strong>A total of nine patients were included in the modified intention-to-treat analysis. The odds of positive <i>M. leprae</i> 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.</p><p><strong>Conclusions: </strong>In patients with multibacillary leprosy, bedaquiline monotherapy cleared <i>M. leprae</i> 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.).</p>","PeriodicalId":54725,"journal":{"name":"New England Journal of Medicine","volume":"391 23","pages":"2212-2218"},"PeriodicalIF":96.2000,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"New England Journal of Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1056/NEJMoa2312928","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
引用次数: 0
Abstract
Background: 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.
Methods: 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 Mycobacterium leprae 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 M. leprae (measured by a quantitative reverse-transcriptase-polymerase-chain-reaction assay).
Results: A total of nine patients were included in the modified intention-to-treat analysis. The odds of positive M. leprae 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.
Conclusions: In patients with multibacillary leprosy, bedaquiline monotherapy cleared M. leprae 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.).
期刊介绍:
The New England Journal of Medicine (NEJM) stands as the foremost medical journal and website worldwide. With an impressive history spanning over two centuries, NEJM boasts a consistent publication of superb, peer-reviewed research and engaging clinical content. Our primary objective revolves around delivering high-caliber information and findings at the juncture of biomedical science and clinical practice. We strive to present this knowledge in formats that are not only comprehensible but also hold practical value, effectively influencing healthcare practices and ultimately enhancing patient outcomes.