Reference: April 2024 | Issue 4 | Vol 10 | Page 4
Highlights from the 2023 Union World Conference on Lung Health, which took place 15-18 November in Paris, France
The Union World Conference on Lung Health is convened annually by the International Union Against Tuberculosis and Lung Disease (The Union) – the world’s first global health organisation, which was established in 1920 with the aim of eradicating tuberculosis (TB) and lung disease.
Its members, staff, and consultants work across more than 140 countries globally. The 2023 conference took place under the theme ‘Transforming Evidence into Practice’.
Despite a notable decline in TB cases in Ireland since the 1950s, the disease has again become a public health priority here and across Europe. A total of 224 cases were notified in Ireland in 2023, and the disease was the most common cause of death among those living with HIV in 2023 globally.
Cases have risen more dramatically in eastern Europe and other parts of the globe, with a substantial increase in multidrug-resistant TB (MDR-TB) posing additional challenges in recent decades.
An array of data was presented during the conference showing the potential efficacy of several new treatment regimens in achieving improved outcomes for patients with MDR-TB. Other major themes during the event included childhood TB, novel treatments, and ineffective policies for managing the disease.
New drug-resistant treatment shows highly effective results in real-world settings
Interim results of a global drug study developed by TB Alliance – the LIFT-TB (Leveraging Innovation for Faster Treatment of Tuberculosis) study – has shown the medication to be highly effective against some of the most challenging strains of tuberculosis (TB).
The three-drug regimen –comprised of bedaquiline, pretomanid, and linezolid (BPaL) – showed a 94.5 per cent cure rate across five of the LIFT-TB countries. The data were presented at the 2023 Union World Conference, and along with results from the Ukraine programme and four abstracts from the Philippines, illustrated several advantages of the BPaL regimen.
In comparison, the global treatment success rate of drug-resistant TB (DR-TB) was about 63 per cent prior to the uptake of new regimens, according to the World Health Organisation (WHO) 2023 Global TB Report.
The BPaL regimen also reduces the length of treatment for DR-TB – which previously took 12-to-18 months or longer – down to six months and is projected to be more cost-effective than previous therapies. Mr Sandeep Juneja, Senior Vice President of Market Access at TB Alliance, said the results “will help drive wider and faster uptake of BPaL”, and that “by acting quickly, other countries and national TB programmes can help save many lives”.
Landmark clinical trial redefines multidrug-resistant TB treatment options
Clinical trial results presented at the 2023 Union World Conference on Lung Health detailed evidence to support the use of four new, improved regimens to treat multidrug resistant- or rifampicin-resistant tuberculosis (MDR/RR-TB). The team, which was led by Médecins Sans Frontières, Partners in Health, and Interactive Research and Development, formed the endTB consortium and began the Phase 3 randomised controlled trial in 2017.
Roughly half a million people contract MDR/RR-TB each year, and although a range of MDR-TB regimens are prescribed around the world, many treatment regimens are long (up to 24 months), ineffective (only 59 per cent treatment success in 2018), and often carry debilitating side-effects.
The trial found three new drug regimens that can deliver similar efficacy and safety to conventional treatments while reducing treatment time by up to two-thirds. The endTB regimens represent important alternatives for shorter MDR-TB treatment and complement the use of BPaL (bedaquiline, pretomanid, and linezolid), which is not suitable for certain populations. If recommended by the World Health Organisation (WHO), these new patient-centred treatment regimens would empower clinicians to offer shortened MDR-TB treatment regardless of age, pregnancy, and comorbidities that are common among people with MDR-TB.
In addition, the trial supports the use of a fourth regimen as an alternative for people who cannot tolerate bedaquiline or linezolid. At least one of these two drugs is in every current WHO-recommended regimen for MDR-TB.
“For far too long, MDR-TB has loomed as a formidable threat with limited, poorly tolerated treatment options, but today, we unveil evidence for multiple innovative, all-oral, shortened regimens that will allow patient-centred, individualised treatment of MDR-TB.
“This marks a pivotal moment in the fight against a disease that has plagued vulnerable populations worldwide. What makes these results even more remarkable is the diversity, and resulting generalisability, of this Phase 3 randomised controlled trial,” said Dr Lorenzo Guglielmetti, Médecins Sans Frontières, Director for the endTB project, and Co-Principal Investigator of the study.
“These results provide new hope for all those awaiting treatment for the most dangerous and difficult-to-treat forms of TB worldwide,” said Dr Philippe Duneton, Executive Director of Unitaid. “We have the gold-standard research. The drugs are already available where they are needed. If recommended, this high-quality evidence could quickly translate into better treatment options suitable for all people with DR-TB.”
The endTB is an international, open-label, Phase 3 non-inferiority, randomised controlled clinical trial comparing five experimental nine-month oral regimens including bedaquiline; delamanid; linezolid; levofloxacin or moxifloxacin; clofazimine; and pyrazinamide to the standard of care in two distinct analysis populations.
The trial enrolled a diverse group of 754 patients from seven countries (Georgia, India, Kazakhstan, Lesotho, Pakistan, Peru, and South Africa). It included historically excluded populations, such as adolescents and those with comorbidities like substance-use disorders, and retained participants who became pregnant during the trial. Randomisation was outcome-adapted, meaning more patients were assigned to regimens that were producing better outcomes.
Regimens 1, 2, and 3 demonstrated non-inferiority to the control in both primary analysis populations, and achieved favourable outcomes in 89 per cent, 90.4 per cent, and 85.2 per cent of participants, respectively. Regimen 5 also showed a strong treatment response at 85.6 per cent and was non-inferior to the control’s 80.7 per cent in one of the primary analysis populations. While consistent results in both populations are needed to formally establish non-inferiority, regimen 5 holds promise as an alternative for patients unable to receive other recommended treatments.
“We stand on the cusp of a significant breakthrough in the battle against MDR, a disease that disproportionately affects impoverished populations around the globe. Our results offer hope to those in dire need and underscore the urgency of continued research and innovation, and accountability of private companies that receive public funds, to address diseases that too often strike the most vulnerable among us.
But the cost of some drugs remains a barrier. One example is delamanid, which is still priced at 12-to-40 times higher than it should be, according to an independently-estimated cost to produce the drug,” said Dr Carole Mitnick, Partners in Health Director of Research for the endTB project, Co-Principal Investigator of the study, and Professor of Global Health and Social Medicine at Harvard Medical School.
The complete endTB trial methodology, regimens, and results are available at: www.endtb.org/.
Novel drug may be a game-changer in TB treatment
Results from preclinical and Phase 1 studies presented at the 2023 Union World Conference showed that the novel drug TBAJ-876 eliminated tuberculosis (TB) bacteria faster and had a potentially safer profile, when compared with bedaquiline.
The new compound could be part of a new combination of drugs that may potentially become a universal regimen, leading to both drug-sensitive and drug-resistant TB (DR-TB) being treated with the same therapy.
Based on these results, a new Pan-Phase 2 trial is underway to test a potential universal regimen. If successful, TBAJ-876 could prove to be part of a single, short, and safe treatment combination. TBAJ-876 is one of several new treatments being hailed as a potential game-changer and a much-needed step forward in the global fight against TB.
Managing TB in children
The World Health Organisation (WHO) launched its roadmap to prevent and treat tuberculosis (TB) in children and adolescents at the 2023 Union World Conference. The roadmap outlines an ambitious five-year plan with 10 key actions to improve the prevention, treatment, and care of TB in young people, and highlights that children and adolescents experience a disproportionate burden of the disease globally.
The WHO recently released its Global Tuberculosis Report, which illustrated that an estimated 1.25 million children and young adolescents became unwell with TB in 2022, making up 12 per cent of the global TB burden. Dr Tereza Kasaeva, Director of WHO Global TB Programme, said it is “unacceptable that hundreds and thousands of children and adolescents worldwide still do not have access to life-saving TB prevention, treatment, and care”.
“The new roadmap lays the groundwork for much needed actions over the next five years, building on commitments made by world leaders at the 2023 UN High Level Meeting on TB, to close gaps in access to care and safeguard the rights of children and adolescents.”
Researchers from Desmond Tutu TB Centre, University of Stellenbosch, South Africa, shared at the event how the risk of developing multidrug-resistant TB (MDR-TB) can be prevented in children. Their study, which was funded by global health initiative Unitaid, among other funders, focused on the antibiotic levofloxacin. The researchers showed that a drug regimen of six months was both safe and effective in preventing the development of MDR-TB in children.
The community-based trial focused on child and adolescent household contacts of adults with MDR-TB in South Africa, and found levofloxacin to be 60 per cent effective in reducing the risk of TB in children. MDR-TB disease in children is complex to treat, requires several antibiotics, and can result in catastrophic costs to children, their families, and healthcare providers. Children with MDR-TB remain one of the most neglected populations affected by the disease, the conference heard.
Current TB policies ‘not enough’
Researchers from the London School of Hygiene and Tropical Medicine have found that half of tuberculosis (TB) transmission occurs before individuals will even access care under existing TB care policies. Research presented at the 2023 Union World Conference revealed how new insights into TB highlight the weakness of current policies designed to eradicate the disease, whereby individuals need to report symptoms in a clinic before receiving care.
The study suggests that one-in-two individuals with subclinical TB, who are likely infectious but are not aware, will not progress to symptoms severe enough for them to seek care.
The amount of transmission missed was reduced to a third if the study assumed a lower relative infectiousness for subclinical TB. The research used a deterministic modelling framework based on 1,000 cohorts of 10,000 individuals.
Prof Rein Houben, Principal Investigator of the European Research Council-funded project said: “The TB community has suspected for a while that current TB policies are not enough to drive TB down. Our work maximised the value of old and new data using mathematical models, and while still in development, our results show just how much transmission is missed, and how many individuals with likely infectious TB will not receive care.”
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