Union position on injectable-free regimens for the treatment of drug-resistant tuberculosis

South Africa recently announced it would be providing all oral-regimens to a majority of persons with rifampicin-resistant tuberculosis (RR-TB)[1] by replacing injectable medicines with bedaquiline. This decision was based on a retrospective cohort analysis from the country showing improved treatment success and reduction of mortality when bedaquiline was given to persons with drug resistant-TB (DR-TB) under programmatic conditions (https://www.thelancet.com/journals/lanres/onlineFirst). 

The Union recognises the challenges—including risk of permanent hearing loss—persons with DR-TB face in the course of receiving injectable medicines as part of a treatment regimen. It also recognises the barriers that injectable medicines place on the scale-up and decentralisation of RR-TB and multidrug-resistant (MDR-TB) care.

There are additional ethical and human rights concerns regarding the use of the injectable agents, particularly if people are not adequately monitored or informed of the potential side-effects of these medications.  Consent is a vital part of RR-TB and MDR-TB treatment, and The Union strongly urges all persons undergoing TB treatment to be fully informed about the risks and benefits of all medications recommended for their treatment so that they are empowered to make informed choices about their treatment.

The Union also recognises the importance of making new medicines available to all  who need them, including children, and supports countries with the introduction and implementation of new developments in TB care. People living with TB deserve access to the best, simplest and least-toxic treatment regimens available.

As a scientific organisation, The Union also recognises the importance of ensuring that all advances in MDR-TB care are evidence-based. The Union supports the role of randomised controlled trials and well-conducted observational studies in driving policy change, ideally using a protocol developed by the Global Drug-Resistance Initiative.

Recent evidence presented by the South African National TB Programme on the use of bedaquiline under programmatic conditions shows the life-saving impact that bedaquiline can have and how it can help patients and health care providers avoid the risk of hearing loss associated with the use of injectable medicines. It is hoped that the excellent results on the use of bedaquiline are confirmed through additional research, including further cohort studies and phase 3 clinical trials. The Union hopes that South Africa will also approve and implement delamanid so programmatic data can be gathered on this other promising drug for DR-TB.

Drug resistance develops over time at the population level in the course of administering antibiotics. The emergence of resistance to bedaquiline is of particular concern for TB given that very few potent drugs are currently available, and recognising the lack of investment in research and development into future new treatments for TB. Given these risks, it is essential to ensure the highest quality of care for patients receiving bedaquiline in order to prevent the emergence and spread of bedaquiline-resistant strains of TB.  In principle, The Union supports ensuring the availability of a 'cascade of regimens'—meaning that individuals who do not respond positively to one treatment regimen are able to access another effective option that will lead to treatment success.