• 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, and Paula Frassinetti Bessa Rebello.
• 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): 221222182212-2218.

BackgroundStandard 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.MethodsIn 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).ResultsA 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.ConclusionsIn 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.).Copyright © 2024 Massachusetts Medical Society.

30 keywords...

hide…