New, safe, and effective tuberculosis treatment options were recently approved by the World Health Organization (WHO). These treatments—which were studied in the Partners In Health (PIH)-led endTB clinical trial—and the resulting recommendations represent the culmination of nearly a decade of scientific research and patient care across 18 countries.
The new treatments will benefit people with some of the most difficult to treat forms of the infectious disease, including multidrug-resistant tuberculosis (MDR-TB) and rifampicin-resistant tuberculosis (RR-TB). Combined with prompt diagnosis, these regimens can improve the lives of countless patients.
For more insight about this major advancement in tuberculosis care, we spoke with Carole Mitnick, PIH’s director of research for the endTB project, co-principal investigator of the endTB trial, and professor of global health and social medicine at Harvard Medical. Below, edited and condensed, are her responses:
How would you summarize the recent news announced by WHO to a non-clinician who is not familiar with tuberculosis, but is eager to learn more?
For the first time ever, virtually everyone with MDR/RR-TB—no matter their age, whether they’re pregnant, whether they have HIV—can get a novel, all-oral, shorter and effective treatment. These new guidelines overcome three major barriers to universal care: 1) With the old standard—a long, toxic, expensive regimen that involved shots every day for six months or longer—health systems could only deliver this complex regimen to a handful of people with MDR/RR-TB each year; 2) the first, shorter, novel regimens had been recommended only for subsets of patients (e.g., adults who weren’t pregnant); 3) because of prior work done by PIH and partners also through the endTB project, there is much more familiarity and comfort among doctors and patients with the drugs in the newly recommended shorter regimens than there was with the first. For all these reasons, the new recommendations should help shorter, effective treatment reach many more people.
Why does this news matter?
Without treatment, MDR/RR-TB transmits in homes and communities and kills people often after a long, debilitating illness. It frequently strikes young adults in the prime of their lives. The number of new cases each year has stubbornly held at roughly half a million. Without these new treatments, we had no hope of ending this scourge.
The endTB project is a collaboration among PIH, Médecins Sans Frontières, and Interactive Research and Development, and funded by Unitaid. What, specifically, was PIH’s role in this work?
PIH led the grant from Unitaid and the endTB project. In all parts of the project, PIH instilled social justice principles, which drives our everyday work. Specifically, PIH enacted these principles through: accompaniment of participants in the endTB clinical trial (and the other studies); provision of social, nutritional, and other forms of support to trial participants; use of modern methods for diagnosis and comprehensive care for side effects; and linkages to other services as needed for other illnesses or economic or social challenges. Essentially, PIH brought the five S’s (staff, stuff, space, systems, and social support) to a clinical trial! PIH led the implementation of the endTB trial in Kazakhstan, Lesotho, and Peru, where the organization has a longstanding presence and critical history of collaboration with each country’s ministry of health.
The new WHO-approved TB drug regimens included children, adolescents, pregnant and breastfeeding women. Why is that important?
These groups are usually excluded from clinical trials to “protect them,” so we don’t know if treatments work the same in them or cause harm. But the reality is that they get MDR/RR-TB and other illnesses that need treatment, so providers are reluctant to use innovations. In the case of MDR-TB/RR-TB, this means they continue to receive older, more toxic regimens that contain many more pills and sometimes injections. Ironically, for pregnant people, many of the drugs used in the old regimens are not known to be safe during pregnancy. So, it’s a terrible situation and vicious cycle.
The endTB regimens used only drugs that are recommended for use in any age group and during pregnancy. Adolescents could join the trial (with permission from a parent or guardian) and people who became pregnant could stay in the study if they chose to. This contributed to the evidence base for the safety of the drugs in pregnancy.
Why is this news especially important for patients with MDR-TB in countries where PIH works, such as Lesotho and Peru, with some of the highest burdens of the disease in the world?
Peru was one of the last countries in the world still using older, injectable-containing, longer regimens. The fact that nearly 40% of endTB participants were enrolled in Peru allowed the Ministry of Health to immediately act upon seeing the results and change practice in October 2023. Even before the WHO recommendation was released, a couple hundred MDR/RR-TB patients in Peru had started an endTB regimen.
Lesotho and Kazakhstan, while quicker to eliminate the injectable agent, had not yet fully adopted shorter, all-oral alternatives. Their participation in the endTB project broadly, and the endTB trial specifically, gave health leaders and providers comfort with the emerging endTB regimens.
Lesotho has a very high rate of HIV infection, which makes people more vulnerable to transmitted MDR/RR-TB. So, interrupting transmission of MDR/RR-TB sooner and more fully with these shortened, effective regimens is key to protecting this vulnerable group from getting sick.
Kazakhstan has one of the highest burdens of MDR/RR-TB in the world. Shorter, effective regimens could allow them to deliver more care in outpatient settings (rather than the norm of hospitalizing them) and, again, contributing to reduced transmission.
How do we hope this news will impact global TB care and financing?
Two of the recommended endTB regimens are the cheapest to purchase on the market. They can be delivered for roughly $300 per treatment course. Using shorter regimens poses less of a burden on health systems and shortens the time people are suffering with the inevitable side effects.
Freed up money used to pay for the other treatments and the additional health services required can be repurposed toward rapid diagnostics. The high price of diagnostic tests limits their use, which, in turn, leaves many people undiagnosed and without treatment. Buying more diagnostics and treating more people will ultimately drive down the burden of disease. Plus, people can go back to work, school, or to taking care of their families sooner.
What are the next steps?
There’s still a lot of work to do to ensure that adequate resources are available to deliver these treatments successfully. The five S’s are more important than ever to ensuring that people can receive a timely diagnosis and complete treatment. PIH is fully invested in initiatives that increase access to even more proven innovation, like the 1/4/6x24 campaign, which draws its inspiration from PIH’s late Co-Founder Dr. Paul Farmer’s commitment to medical science and health as a human right, and PIH Co-Founder Dr. Jim Yong Kim’s aspirational 3x5 initiative for scaling up access to HIV care in low-income countries.
PIH’s involvement in advocacy efforts to squash efforts to create “patent thickets” or “evergreen patents” means that critical drugs, like bedaquiline, are much cheaper than they would otherwise be. And the Time for $5 campaign, in which PIH is a partner, has also yielded a key win in a 20% reduction in the price of the key diagnostic tool to establish the presence of RR-TB. Our work isn’t done there as the price is still not set at a level equivalent to cost plus a reasonable profit, which is $5 as estimated by our friends at MSF. And many other tests made by the same manufacturer at the same cost, which are key to improving health in the places we work, are still priced much too high. We are also working to increase funding for TB in the U.S. budget.
What else should the world know about tuberculosis and the work PIH is doing to treat patients with this deadly but curable infectious disease?
Exactly that: TB newly affects 10 million people each year and close to 1.5 million die. But TB is curable and preventable. PIH is at the forefront of bringing all the available tools (the 5 S’s) to bear on this scourge to stop stupid deaths in the places we work. Through efforts like endTB, PIH is also pioneering research to improve the available tools. And, PIH doesn’t stop there, it makes sure that these new tools are taken up by countries and providers who see a lot of TB. PIH works tirelessly to increase the pot of resources available to those facing this disease.
Originally published on pih.org
