Correspondence
disease attributable to either tobacco smoking or tuberculosis2,4 and their potential combined effect, it is crucial that smoking cessation interventions form part of national tuberculosis control and prevention programmes, and countries with a high burden of tuberculosis need to develop clinical and public health strategies to manage patients with COPD. GBM reports grants from AstraZeneca and has served on an advisory board for Novartis. All other authors declare no competing interests.
*Anthony L Byrne, Ben J Marais, Carole D Mitnick, Leonid Lecca, Guy B Marks [email protected] The University of Sydney, Sydney, NSW, Australia (ALB, BJM, GBM); Socios En Salud Sucursal (Partners In Health), Lima, Perú (ALB, CDM, LL); Centre for Research Excellence in, Sydney, NSW, Australia (ALB, BJM, CDM, LL); Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Sydney, NSW, Australia (BJM); and Harvard Medical School, Boston, MA, USA (CDM) 1
2 3
4
5
Postma DS, Bush A, Van Den Berge M. Risk factors and early origins of chronic obstructive pulmonary disease. Lancet 2015; 385: 899–909. WHO. Global tuberculosis report 2014. Geneva: World Health Organization, 2014. Byrne AL, Marais BJ, Mitnick CD, Lecca L, Marks GB. Tuberculosis and chronic respiratory disease: a systematic review. Int J Infect Dis 2015; 32: 138–46. Lopez AD, Mathews CD, Ezzati M, Jamison DT, Murray CJL. Global burden of disease and risk factors. Washington: The World Bank, 2006. Van Zyl Smit RN, Pai M, Yew WW, et al. Global lung health: the colliding epidemics of tuberculosis, tobacco smoking, HIV and COPD. Eur Respir J 2010; 35: 27–33.
Informed use of bedaquiline for tuberculosis
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.2 In view of the small number of American patients receiving bedaquiline and to avoid selection bias, the inclusion of all recipients of bedaquiline in this registry is essential.2 Yet bedaquiline’s prospective registry opened in March, 2014, missing all the patients who started on the drug since the approval in December, 2012. The registry was developed without consulting end users and little has been done to inform prescribers about its existence. Clinicians who attempt to report in to the registry find the forms onerous and unclear. Importantly, consent forms are only available in English, despite the documented frequency of tuberculosis cases in foreign-born people.3 A simple, clear, and widely accessible process is urgently needed to gather crucial safety information from patients and providers. Results must be shared with FDA and with researchers and the public. We declare no competing interests.
*Erica M Lessem, John Bernardo, Caitlin Reed, Donna H Wegener [email protected] Treatment Action Group, New York, NY 10016-7701, USA (EML); Boston University School of Medicine, Boston, MA, USA (JB); Olive View-UCLA Medical Center Inpatient Tuberculosis Unit, Division of Infectious Diseases, Department of Medicine and David Geffen School of Medicine, UCLA, Los Angeles, CA, USA (CR); and National Tuberculosis Controllers Association, Smyrna, GA, USA (JB, DHW) 1
In 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 1724
2
3
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. US Food and Drug Administration. Postmarketing requirements and commitments: Sirturo. August 2013. http:// www.accessdata.fda.gov/scripts/cder/pmc/ index.cfm (accessed July 18, 2014). Centers for Disease Control and Prevention. Reported tuberculosis in the United States, 2012. Atlanta, USA: 2013. http://www.cdc. gov/tb/statistics/reports/2012/pdf/ report2012.pdf (accessed July 18, 2014).
The 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.3 TBA have also decided to test the PaMZ regimen in a 4-month treatment-shortening trial. Few data support the use of this combination for treatment-shortening and this regimen might not be robust enough, in view of the results of other treatment-shortening trials.4 Another concern in STAND TB is the proposed use of PaMZ for patients with multidrug-resistant tuberculosis. Three-drug combinations have never been shown to be successful for the treatment of multidrug-resistant tuberculosis in any setting. In view of the high likelihood of developing resistance to the nitroimidazoles, there are also concerns about resistance amplification.5 Better treatment for multidrug-resistant tuberculosis is urgently needed, but safety and resistance amplification cannot be overlooked. Unfortunately, TBA is waiting to test the drug in more robust combinations for multidrug-resistant tuberculosis until it has been used for six months in the STAND-TB regimens. Much work is needed to improve care for patients with tuberculosis and multidrug resistant tuberculosis. The need for such radical changes, however, should not ignore the risks for patients inherent in such trials. I declare no competing interests.
Jennifer Furin [email protected]
www.thelancet.com Vol 385 May 2, 2015
disease attributable to either tobacco smoking or tuberculosis2,4 and their potential combined effect, it is crucial that smoking cessation interventions form part of national tuberculosis control and prevention programmes, and countries with a high burden of tuberculosis need to develop clinical and public health strategies to manage patients with COPD. GBM reports grants from AstraZeneca and has served on an advisory board for Novartis. All other authors declare no competing interests.
*Anthony L Byrne, Ben J Marais, Carole D Mitnick, Leonid Lecca, Guy B Marks [email protected] The University of Sydney, Sydney, NSW, Australia (ALB, BJM, GBM); Socios En Salud Sucursal (Partners In Health), Lima, Perú (ALB, CDM, LL); Centre for Research Excellence in, Sydney, NSW, Australia (ALB, BJM, CDM, LL); Marie Bashir Institute for Infectious Diseases and Biosecurity, University of Sydney, Sydney, NSW, Australia (BJM); and Harvard Medical School, Boston, MA, USA (CDM) 1
2 3
4
5
Postma DS, Bush A, Van Den Berge M. Risk factors and early origins of chronic obstructive pulmonary disease. Lancet 2015; 385: 899–909. WHO. Global tuberculosis report 2014. Geneva: World Health Organization, 2014. Byrne AL, Marais BJ, Mitnick CD, Lecca L, Marks GB. Tuberculosis and chronic respiratory disease: a systematic review. Int J Infect Dis 2015; 32: 138–46. Lopez AD, Mathews CD, Ezzati M, Jamison DT, Murray CJL. Global burden of disease and risk factors. Washington: The World Bank, 2006. Van Zyl Smit RN, Pai M, Yew WW, et al. Global lung health: the colliding epidemics of tuberculosis, tobacco smoking, HIV and COPD. Eur Respir J 2010; 35: 27–33.
Informed use of bedaquiline for tuberculosis
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.2 In view of the small number of American patients receiving bedaquiline and to avoid selection bias, the inclusion of all recipients of bedaquiline in this registry is essential.2 Yet bedaquiline’s prospective registry opened in March, 2014, missing all the patients who started on the drug since the approval in December, 2012. The registry was developed without consulting end users and little has been done to inform prescribers about its existence. Clinicians who attempt to report in to the registry find the forms onerous and unclear. Importantly, consent forms are only available in English, despite the documented frequency of tuberculosis cases in foreign-born people.3 A simple, clear, and widely accessible process is urgently needed to gather crucial safety information from patients and providers. Results must be shared with FDA and with researchers and the public. We declare no competing interests.
*Erica M Lessem, John Bernardo, Caitlin Reed, Donna H Wegener [email protected] Treatment Action Group, New York, NY 10016-7701, USA (EML); Boston University School of Medicine, Boston, MA, USA (JB); Olive View-UCLA Medical Center Inpatient Tuberculosis Unit, Division of Infectious Diseases, Department of Medicine and David Geffen School of Medicine, UCLA, Los Angeles, CA, USA (CR); and National Tuberculosis Controllers Association, Smyrna, GA, USA (JB, DHW) 1
In 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 1724
2
3
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. US Food and Drug Administration. Postmarketing requirements and commitments: Sirturo. August 2013. http:// www.accessdata.fda.gov/scripts/cder/pmc/ index.cfm (accessed July 18, 2014). Centers for Disease Control and Prevention. Reported tuberculosis in the United States, 2012. Atlanta, USA: 2013. http://www.cdc. gov/tb/statistics/reports/2012/pdf/ report2012.pdf (accessed July 18, 2014).
The 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.3 TBA have also decided to test the PaMZ regimen in a 4-month treatment-shortening trial. Few data support the use of this combination for treatment-shortening and this regimen might not be robust enough, in view of the results of other treatment-shortening trials.4 Another concern in STAND TB is the proposed use of PaMZ for patients with multidrug-resistant tuberculosis. Three-drug combinations have never been shown to be successful for the treatment of multidrug-resistant tuberculosis in any setting. In view of the high likelihood of developing resistance to the nitroimidazoles, there are also concerns about resistance amplification.5 Better treatment for multidrug-resistant tuberculosis is urgently needed, but safety and resistance amplification cannot be overlooked. Unfortunately, TBA is waiting to test the drug in more robust combinations for multidrug-resistant tuberculosis until it has been used for six months in the STAND-TB regimens. Much work is needed to improve care for patients with tuberculosis and multidrug resistant tuberculosis. The need for such radical changes, however, should not ignore the risks for patients inherent in such trials. I declare no competing interests.
Jennifer Furin [email protected]
www.thelancet.com Vol 385 May 2, 2015
