title: Bedaquiline in the treatment of multidrug- and extensively drug-resistant tuberculosis.
abstract: Bedaquiline, a diarylquinoline, improved cure rates when added to a multidrug-resistant tuberculosis (MDR-TB) treatment regimen in a previous placebo-controlled, phase 2 trial (TMC207-C208; NCT00449644). The current phase 2, multicenter, open-label, single-arm trial (TMC207-C209; NCT00910871) reported here was conducted to confirm the safety and efficacy of bedaquiline.Newly diagnosed or previously treated patients with MDR-TB (including pre-extensively drug-resistant (pre-XDR)-TB or extensively drug-resistant (XDR)-TB) received bedaquiline for 24 weeks with a background regimen of anti-TB drugs continued according to National TB Programme treatment guidelines. Patients were assessed during and up to 120 weeks after starting bedaquiline.Of 233 enrolled patients, 63.5% had MDR-TB, 18.9% had pre-XDR-TB and 16.3% had XDR-TB, with 87.1% having taken second-line drugs prior to enrolment. 16 patients (6.9%) died. 20 patients (8.6%) discontinued before week 24, most commonly due to adverse events or MDR-TB-related events. Adverse events were generally those commonly associated with MDR-TB treatment. In the efficacy population (n=205), culture conversion (missing outcome classified as failure) was 72.2% at 120 weeks, and 73.1%, 70.5% and 62.2% in MDR-TB, pre-XDR-TB and XDR-TB patients, respectively.Addition of bedaquiline to a background regimen was well tolerated and led to good outcomes in this clinically relevant patient cohort with MDR-TB.
authors.affiliation: Medical Research Council and Kwazulu Research Institute for TB and HIV (K-RITH), Durban, South Africa Alex.Pym@k-rith.org.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Pym
authors.affiliation: Division of Medical Physiology and Dept of Science and Technology/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research and Medical Research Council Centre for Tuberculosis Research, Faculty of Medicine and Health Sciences, University of Stellenbosch, Cape Town, South Africa.
authors.forename: Andreas H
authors.initials: AH
authors.lastname: Diacon
authors.affiliation: Tuberculosis Dept, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumour Research Institute, Beijing, China.
authors.forename: Shen-Jie
authors.initials: SJ
authors.lastname: Tang
authors.affiliation: Clinical HIV Research Unit, Dept of Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Francesca
authors.initials: F
authors.lastname: Conradie
authors.affiliation: Tartu University Lung Hospital, Tartu, Estonia.
authors.forename: Manfred
authors.initials: M
authors.lastname: Danilovits
authors.affiliation: Chest Disease Institute, Ministry of Public Health, Nonthaburi, Thailand.
authors.forename: Charoen
authors.initials: C
authors.lastname: Chuchottaworn
authors.affiliation: Central Tuberculosis Research Institute, Russian Academy of Medical Sciences, Moscow, Russia.
authors.forename: Irina
authors.initials: I
authors.lastname: Vasilyeva
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Andries
authors.affiliation: Janssen Research & Development LLC, Titusville, NJ, USA.
authors.forename: Nyasha
authors.initials: N
authors.lastname: Bakare
authors.affiliation: Janssen Research & Development LLC, Titusville, NJ, USA.
authors.forename: Tine
authors.initials: T
authors.lastname: De Marez
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors.forename: Myriam
authors.initials: M
authors.lastname: Haxaire-Theeuwes
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors.forename: Nacer
authors.initials: N
authors.lastname: Lounis
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: Meyvisch
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors.forename: Ben
authors.initials: B
authors.lastname: Van Baelen
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors.forename: Rolf P G
authors.initials: RP
authors.lastname: van Heeswijk
authors.affiliation: Janssen Research & Development LLC, Titusville, NJ, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Dannemann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000627:therapeutic use*; D064687:Diarylquinolines / Q000627:therapeutic use*; D054908:Extensively Drug-Resistant Tuberculosis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D064687:Diarylquinolines; C493870:bedaquiline