The use of bedaquiline in regimens to treat drug-resistant and drug-susceptible tuberculosis: a perspective from tuberculosis-affected communities

Abstract

In December, 2012, the US Food and Drug Administration (FDA) approved bedaquiline for the treatment of pulmonary drug-resistant tuberculosis. 1 Edney A J&J Sirturo wins FDA approval to treat drug-resistant TB. Bloomberg News. Dec 31, 2012. http://www.bloomberg.com/news/2012-12-31/j-j-sirturo-wins-fda-approval-to-treat-drug-resistant-tb.html Google Scholar WHO has issued normative guidance on bedaquiline, 2 World Health OrganizationThe use of bedaquiline in the treatment of multidrug resistant tuberculosis expert group meeting report. World Health Organization, Geneva2013: 1-31http://www.who.int/tb/challenges/mdr/bedaquiline/en/index.html Google Scholar which is available on the market in the USA and through compassionate use in other countries. As the first new drug from a novel class approved to treat tuberculosis in more than 40 years, bedaquiline's implications for improving treatment of drug-resistant tuberculosis and possible application to create shorter first-line regimens for treatment of drug-susceptible tuberculosis is still unclear. Existing drugs must be taken for months (drug-susceptible tuberculosis) or years (drug-resistant tuberculosis), burdening patients and health systems; even then, cure rates for drug-resistant disease range from 11% to 79% dependent on the extent of resistance. 3 Orenstein EW Basu S Shah NS et al. Treatment outcomes among patients with multidrug-resistant tuberculosis: systematic review and meta-analysis. Lancet Infect Dis. 2009; 9: 153-161 Summary Full Text Full Text PDF PubMed Scopus (464) Google Scholar , 4 Pietersen E Ignatius E Streicher EM et al. Long-term outcomes of patients with extensively drug-resistant tuberculosis in South Africa: a cohort study. Lancet. 2014; 383: 1230-1239 Summary Full Text Full Text PDF PubMed Scopus (184) Google Scholar However, community voices on bedaquiline's use to treat drug-resistant tuberculosis and future development as a potential treatment for drug-susceptible disease have been largely unheard. We provide a community perspective on this issue and list seven questions concerning bedaquiline's safety that researchers should answer before the launch of clinical trials of bedaquiline for drug-susceptible tuberculosis. Informed use of bedaquiline for tuberculosisThe Viewpoint by Laia Ruiz Mingote and colleagues1 raises safety concerns regarding bedaquiline in treatment shortening trials for pan-resistant tuberculosis (tuberculosis that is susceptible to all first-line antituberculosis treatments). A trial with similar issues is STAND TB, by the Global Alliance for TB Drug Development (TBA), which is testing the nitroimidazole PA-824 (pretomanid) in combination with pyrazinamide and moxifloxacin (PaMZ).2 There are little safety data on the use of PA-824 longer than 8 weeks, and both PA-824 and moxifloxacin have significant toxic effects. Full-Text PDF Informed use of bedaquiline for tuberculosisIn their Viewpoint (Jan 31, p 477),1 Laia Ruiz Mingote and colleagues highlight the urgent need for additional safety data on bedaquiline, the first new tuberculosis drug to receive US Food and Drug Administration (FDA) approval in more than 40 years. Because the drug received accelerated approval based solely on phase 2 studies, critical safety data for bedaquiline are incomplete. In view of the scarcity of data, increased mortality in the bedaquiline group of one phase 2 trial, and public health importance of the drug, the FDA's accelerated approval required that a patient registry be set up to assess serious adverse events, including death. Full-Text PDF Informed use of bedaquiline for tuberculosis–Authors' replyWe thank Erica Lessem and colleagues for commenting on our Viewpoint1 regarding the challenges surrounding the bedaquiline patient registry in the USA. For drugs like bedaquiline that receive accelerated approval, patient registries are a critical mechanism for collecting safety data on new drugs. Recent data from the US Centers for Disease Control and Prevention indicate that the tuberculosis epidemic in the USA is marked by increasing racial and ethnic disparities, and concentrated among foreign-born people. Full-Text PDF