Ilaria Motta: A new awakening in TB—it’s time to be aware of where we are and where we’re going

TB care has come a long way in recent years, says Ilaria Motta, but there are still obstacles to patients receiving new treatments

Over the past three or four years, the treatment for rifampicin resistant (RR) tuberculosis has undergone many changes. New drugs, such as bedaquiline and delamanid, came on to the market, the duration of treatment for fluoroquinolone susceptible patients decreased from 20-24 months to 9-11 months, and in the past year painful injections were replaced with a shorter full oral regimen. 

What does this potentially mean for people with RR-TB in 2020? Imagine yourself or your relative with a better quality of life; suffering less without daily painful injections; taking better tolerated drugs with fewer adverse events; and going back to work almost one year earlier than you previously would have been able to, with some indirect savings for the entire family.

Wouldn’t everyone want this option? 

It’s a rhetorical question, of course, but it’s of paramount importance that we always keep the patient, the end user, at the centre of the discussion. Although scientific progress is essential, several external factors could stop the above scenario from becoming a reality for everyone.

The delayed uptake of new recommendations from the World Health Organization (WHO) in single national guidelines, the pending approval at a country level of new drugs, and limited drug supply are just some of the factors that can hamper the delivery of new RR TB treatments. 

For example, in South Africa the short course regimen with bedaquiline was approved in July 2018 and contributed to new WHO recommendations, but delamanid was only registered in March 2019. In other countries, health ministries are still hesitant to implement the use of extended durations of bedaquiline and delamanid beyond the approved 24 weeks. 

Moreover, to deliver new treatments safely, we need to invest more effort in widening the availability of drugs sensitivity testing (DST), supportive care for adverse events, and adherence support. 

As a physician and clinical researcher, I am witnessing the emergence of new evidence on RR-TB treatments in a relatively short time period. One of the main consequences of this is the unavoidable creation of a puzzle of different standard of care regimens across the world.

We are moving away from a “one size fits all” model, and standardised treatment won’t be the solution (as, for example, happened with pangenotypic hepatitis C treatment). We are shifting from defining patients as having MDR/XDR-TB to fluoroquinolone resistant/susceptible TB, and the design of future studies, regimens, and guidelines are all following suit. 

It is critical that our patients with RR-TB are engaged through all the cascade of care, with all the different providers involved. TB physicians have a key role in keeping patients informed, but the transfer of knowledge also passes through local general practitioners and patients’ groups. To ensure that all the information communicated is correct and up to date, education is key. 

Patients can participate in studies so that they have access to new drugs and regimens in places where they otherwise would be difficult to get. Yet for these patients, these concepts, along with the risks and benefits, should be clearly explained. 

From a researcher’s perspective, the shift to different treatments and regimens across different settings in such a short time period has its difficulties. Assessing the impact of multiple studies with different designs is not always that straightforward. Comparing the outcomes of new regimens in clinical trials with different standards of care (according to the various settings and changes over time) could result in samples that are not powered enough to give statistical significance.

Observational studies and clinical trials in patients with RR-TB are notably known for their long duration (on average two to five years), compared to, for example, trials in malaria treatment that typically last a few days or weeks. By the time the results are available for RR-TB trials, there is a risk that the investigational arms will be similar to the control arm, and the expected value of the study will be lost.

In our fight to end TB, it’s vital to acknowledge the achievements that we’ve made in RR-TB treatment, but we need to recognise the limits too. The transmission of TB strains that are resistant to bedaquiline is already a reality, the tools we have to monitor drug sensitivity are not yet widely used, and the cost of new drugs is still prohibitive for many countries.

We cannot claim victory yet, but it’s time to understand where we are, accept the limits, and plan what we do next.

Ilaria Motta is an infectious diseases physician with experience in managing HIV and TB infections in resource limited settings. She is currently working as a medical monitor for the TB-PRACTECAL clinical trial with MSF-UK, and she collaborates as a clinical adviser to the EndTB clinical trial with MSF-France.

Competing interests: I am working with MSF-UK as a medical monitor and clinical adviser for TB-PRACTECAL (a clinical trial on RR-TB) and I am a member of the clinical advisory committee in EndTB (a clinical trial on RR-TB by MSF-FRANCE and Partners in Health). I have no other competing interests to declare.