Correspondence
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Ruiz Mingote L, Namutamba D, Apina F, et al. The use of bedaquiline in regimens to treat drug-resistant and drug-susceptible tuberculosis: a perspective from tuberculosis affected communities. Lancet 2015; 385: 477–79. TB Alliance. New tuberculosis drug regimen will move to landmark phase 3 clinical trial. http://www.tballiance.org/newscenter/ viewbrief.php?id=1096 (accessed July 15, 2014). Dawson R, Diacon A, Everitt D, et al. Efficiency and safety of the combination of moxifloxacin, pretomanid (PA-824), and pyrazinamide during the first 8 weeks of antituberculosis treatment: a phase 2b, open-label, partly randomised trial in patients with drugsusceptible or drug-resistant pulmonary tuberculosis. Lancet 2015; published online March 17. http://dx.doi.org/10.1016/S01406736(14)62002-X. Merle CS, Sisimanadis C, Sow OB, et al. A pivotal registration phase III multicenter, randomized tuberculosis controlled trial: design issues and lessons learnt from the Gatifloxacin for TB (OFLOTUB) project. Trials 2012; 13: 61. Manjunatha U, Boshoff H, Dowd C, et al. Identification of a nitroimidazo-oxazinespecific protein involved in PA-824 resistance in Mycobacterium tuberculosis. Proc Natl Acad Sci USA 2006; 103: 431–36.
Authors’ reply We 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. 2 It is essential that patient registries be made inclusive by facilitating the enrolment of non-native English speakers and susceptible populations. The inconsistencies that characterise tuberculosis epidemics should not be mirrored in the collection of drug safety data. Collecting important safety data on bedaquiline should also be facilitated globally. Global health institutions should support www.thelancet.com Vol 385 May 2, 2015
tuberculosis programmes with technical assistance, and create a multinational programme of data collection, analysis, and dissemination to facilitate WHO– recommended pharmacovigilance of new tuberculosis drugs. 3 The National Bedaquiline Clinical Access Program in South Africa offers one example of a successful monitoring programme.4 Importantly, it collects data on bedaquiline’s safety when given to patients with drug-resistant tuberculosis, or patients with HIV who are taking antiretrovirals—a patient population excluded from the phase 2 trials supporting bedaquiline’s approval. Although data from observational cohort studies are not as useful as evaluation of bedaquiline’s safety and efficacy in phase 3 clinical trials, interim analysis of 91 patients receiving bedaquiline in South Africa’s clinical access programme, presented in October, 2014, provide encouraging information on bedaquiline’s safety in the absence of further trials data.5 Further clinical trials for new tuberculosis drugs, including a phase 3 trial of bedaquiline, are still necessary. Jennifer Furin raises concerns about the evaluation of PA-824 (pretomanid) in combination with pyrazinamide and moxifloxacin in the Global Alliance for TB Drug Development’s STAND trial. Our community advisory board, the Community Research Advisors Group, does not advise the Global Alliance for TB Drug Development and cannot comment on the specifics of pretomanid’s development. Furin also notes the Global Alliance for TB Drug Development’s decision not to provide pretomanid to a proposed AIDS Clinical Trials Group study. Investigators have reported similar difficulties in acquiring bedaquiline for further studies. Increasingly, access to new compounds is a challenge not only for communities affected by tuberculosis, but also for researchers. New tuberculosis drugs
such as bedaquiline and delamanid must be available for researchers to study in different combinations to arrive at optimum treatment options. We call on tuberculosis drug developers to work together in the best interests of patients and communities.
GUSTOIMAGES/Science Photo Library
Case Western Reserve University, TB Research Unit, Cleveland, OH 44106, USA
MWF has received grants from the Global Alliance for TB Drug Development and the Stop TB Partnership for projects outside the submitted work. All other authors declare no competing interests.
Laia Ruiz Mingote, Dorothy Namutamba, Barbara Seaworth, Cynthia Lee, *Mike Watson Frick [email protected] Community Research Advisors Group, New York, NY, USA (LRM, DN, BS, CL); and Treatment Action Group, New York, NY 10016, USA (MWF) 1
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Ruiz Mingote L, Namutamba D, Apina F, et al. The use of bedaquiline in regimens to treat drug-resistant and drug-susceptible tuberculosis: a perspective from tuberculosisaffected communities. Lancet 2015; 385: 477–79. Scott C, Kirking H, Jeffries C, Price S, Pratt R. Tuberculosis trends—United States, 2014. MMWR Morb Mortal Wkly Rep 2015; 64: 265–69. WHO. The use of bedaquiline in the treatment of multidrug resistant tuberculosis: expert group meeting report. Geneva: January 29–30, 2013. http://www.who.int/tb/challenges/ mdr/Report_EGM_BDQ_2013.pdf (accessed March 25, 2015). Conradie F, Meintjes G, Hughes J, et al. Clinical access to bedaquiline programme for the treatment of drug-resistant tuberculosis. S Afr Med J 2014; 104: 164–66. Ndjeka N, Conradie F, Hughes J, et al. Safe and effective bedaquiline treatment of drug resistant tuberculosis (DR-TB) within the National Bedaquiline Clinical Access Programme in South Africa. 45th Union World Conference on Lung Health, Oct 28–Nov 1, 2014, Barcelona.
Dengue vaccine—time to act now Maria Rosario Capeding and colleagues (Oct 11, p 1358) 1 have demonstrated the efficacy and safety of a dengue vaccine in a study conducted in five Asian countries where more than 1 in 25 unvaccinated children suffered a symptomatic dengue episode each year. With 56·5% (95% CI 43·8–66·4) overall 1725
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Ruiz Mingote L, Namutamba D, Apina F, et al. The use of bedaquiline in regimens to treat drug-resistant and drug-susceptible tuberculosis: a perspective from tuberculosis affected communities. Lancet 2015; 385: 477–79. TB Alliance. New tuberculosis drug regimen will move to landmark phase 3 clinical trial. http://www.tballiance.org/newscenter/ viewbrief.php?id=1096 (accessed July 15, 2014). Dawson R, Diacon A, Everitt D, et al. Efficiency and safety of the combination of moxifloxacin, pretomanid (PA-824), and pyrazinamide during the first 8 weeks of antituberculosis treatment: a phase 2b, open-label, partly randomised trial in patients with drugsusceptible or drug-resistant pulmonary tuberculosis. Lancet 2015; published online March 17. http://dx.doi.org/10.1016/S01406736(14)62002-X. Merle CS, Sisimanadis C, Sow OB, et al. A pivotal registration phase III multicenter, randomized tuberculosis controlled trial: design issues and lessons learnt from the Gatifloxacin for TB (OFLOTUB) project. Trials 2012; 13: 61. Manjunatha U, Boshoff H, Dowd C, et al. Identification of a nitroimidazo-oxazinespecific protein involved in PA-824 resistance in Mycobacterium tuberculosis. Proc Natl Acad Sci USA 2006; 103: 431–36.
Authors’ reply We 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. 2 It is essential that patient registries be made inclusive by facilitating the enrolment of non-native English speakers and susceptible populations. The inconsistencies that characterise tuberculosis epidemics should not be mirrored in the collection of drug safety data. Collecting important safety data on bedaquiline should also be facilitated globally. Global health institutions should support www.thelancet.com Vol 385 May 2, 2015
tuberculosis programmes with technical assistance, and create a multinational programme of data collection, analysis, and dissemination to facilitate WHO– recommended pharmacovigilance of new tuberculosis drugs. 3 The National Bedaquiline Clinical Access Program in South Africa offers one example of a successful monitoring programme.4 Importantly, it collects data on bedaquiline’s safety when given to patients with drug-resistant tuberculosis, or patients with HIV who are taking antiretrovirals—a patient population excluded from the phase 2 trials supporting bedaquiline’s approval. Although data from observational cohort studies are not as useful as evaluation of bedaquiline’s safety and efficacy in phase 3 clinical trials, interim analysis of 91 patients receiving bedaquiline in South Africa’s clinical access programme, presented in October, 2014, provide encouraging information on bedaquiline’s safety in the absence of further trials data.5 Further clinical trials for new tuberculosis drugs, including a phase 3 trial of bedaquiline, are still necessary. Jennifer Furin raises concerns about the evaluation of PA-824 (pretomanid) in combination with pyrazinamide and moxifloxacin in the Global Alliance for TB Drug Development’s STAND trial. Our community advisory board, the Community Research Advisors Group, does not advise the Global Alliance for TB Drug Development and cannot comment on the specifics of pretomanid’s development. Furin also notes the Global Alliance for TB Drug Development’s decision not to provide pretomanid to a proposed AIDS Clinical Trials Group study. Investigators have reported similar difficulties in acquiring bedaquiline for further studies. Increasingly, access to new compounds is a challenge not only for communities affected by tuberculosis, but also for researchers. New tuberculosis drugs
such as bedaquiline and delamanid must be available for researchers to study in different combinations to arrive at optimum treatment options. We call on tuberculosis drug developers to work together in the best interests of patients and communities.
GUSTOIMAGES/Science Photo Library
Case Western Reserve University, TB Research Unit, Cleveland, OH 44106, USA
MWF has received grants from the Global Alliance for TB Drug Development and the Stop TB Partnership for projects outside the submitted work. All other authors declare no competing interests.
Laia Ruiz Mingote, Dorothy Namutamba, Barbara Seaworth, Cynthia Lee, *Mike Watson Frick [email protected] Community Research Advisors Group, New York, NY, USA (LRM, DN, BS, CL); and Treatment Action Group, New York, NY 10016, USA (MWF) 1
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Ruiz Mingote L, Namutamba D, Apina F, et al. The use of bedaquiline in regimens to treat drug-resistant and drug-susceptible tuberculosis: a perspective from tuberculosisaffected communities. Lancet 2015; 385: 477–79. Scott C, Kirking H, Jeffries C, Price S, Pratt R. Tuberculosis trends—United States, 2014. MMWR Morb Mortal Wkly Rep 2015; 64: 265–69. WHO. The use of bedaquiline in the treatment of multidrug resistant tuberculosis: expert group meeting report. Geneva: January 29–30, 2013. http://www.who.int/tb/challenges/ mdr/Report_EGM_BDQ_2013.pdf (accessed March 25, 2015). Conradie F, Meintjes G, Hughes J, et al. Clinical access to bedaquiline programme for the treatment of drug-resistant tuberculosis. S Afr Med J 2014; 104: 164–66. Ndjeka N, Conradie F, Hughes J, et al. Safe and effective bedaquiline treatment of drug resistant tuberculosis (DR-TB) within the National Bedaquiline Clinical Access Programme in South Africa. 45th Union World Conference on Lung Health, Oct 28–Nov 1, 2014, Barcelona.
Dengue vaccine—time to act now Maria Rosario Capeding and colleagues (Oct 11, p 1358) 1 have demonstrated the efficacy and safety of a dengue vaccine in a study conducted in five Asian countries where more than 1 in 25 unvaccinated children suffered a symptomatic dengue episode each year. With 56·5% (95% CI 43·8–66·4) overall 1725
