1. Bedaquiline in the treatment of multidrug- and extensively drug-resistant tuberculosis
- Author
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Alexander S, Pym, Andreas H, Diacon, Shen-Jie, Tang, Francesca, Conradie, Manfred, Danilovits, Charoen, Chuchottaworn, Irina, Vasilyeva, Koen, Andries, Nyasha, Bakare, Tine, De Marez, Myriam, Haxaire-Theeuwes, Nacer, Lounis, Paul, Meyvisch, Ben, Van Baelen, Rolf P G, van Heeswijk, Brian, Dannemann, and Xia, Zhang
- Subjects
Adult ,Male ,0301 basic medicine ,Pulmonary and Respiratory Medicine ,Pediatrics ,medicine.medical_specialty ,Tuberculosis ,Adolescent ,Extensively Drug-Resistant Tuberculosis ,030106 microbiology ,Population ,Antitubercular Agents ,Young Adult ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Tuberculosis, Multidrug-Resistant ,medicine ,Culture conversion ,Humans ,Diarylquinolines ,education ,Adverse effect ,Aged ,education.field_of_study ,business.industry ,Extensively drug-resistant tuberculosis ,Middle Aged ,medicine.disease ,Clinical trial ,Regimen ,Treatment Outcome ,030228 respiratory system ,chemistry ,Female ,Bedaquiline ,business - 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.
- Published
- 2015
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