Bedaquiline in the treatment of multidrug- and extensively drug-resistant tuberculosis
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, TMC207-C209 Study Group, Francesca Conradie, Xiaohong Chen, Naihui Chu, Charoen Chuchottaworn, Manfred Danilovits, Jorge De Los Rios, Andreas Diacon, Dina Diaz, Vladislav Erokhin, Irina Vasilyeva, Victor Flores, Sung Chul Hwang, Carlos Iberico, Boris Kazennyi, Young Sam Kim, Anu Kurve, Mykhaylo Kuzhko, O Jung Kwon, Vaira Leimane, Svetlana Lyepshina, Andrey Maryandyshev, Vasiliy Melnyk, Ronelle Narasimooloo, Alexander Pym, Lihua Qiu, Gönenç Ortaköylü, Seref Ozkara, Rafael Reano, Tae Sun Shim, Shen-Jie Tang, Eduardo Ticona Chavez, Tawatchai Wiwatworapan, Xia Zhang, 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, TMC207-C209 Study Group, Francesca Conradie, Xiaohong Chen, Naihui Chu, Charoen Chuchottaworn, Manfred Danilovits, Jorge De Los Rios, Andreas Diacon, Dina Diaz, Vladislav Erokhin, Irina Vasilyeva, Victor Flores, Sung Chul Hwang, Carlos Iberico, Boris Kazennyi, Young Sam Kim, Anu Kurve, Mykhaylo Kuzhko, O Jung Kwon, Vaira Leimane, Svetlana Lyepshina, Andrey Maryandyshev, Vasiliy Melnyk, Ronelle Narasimooloo, Alexander Pym, Lihua Qiu, Gönenç Ortaköylü, Seref Ozkara, Rafael Reano, Tae Sun Shim, Shen-Jie Tang, Eduardo Ticona Chavez, Tawatchai Wiwatworapan, Xia Zhang
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.
Copyright ©ERS 2016.
Source: PubMed