Symposium 20 - APRC 2024

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Symposium 20：Programmatic Management of DSTB: Progress and Challenges

Standard regimen with 2HERZ/4HER was very effective for drug susceptible tuberculosis. However, it was still too long for TB patient and also had many side effects like hepatitis which will interrupt TB treatment. To find short course regimen less than 4 months for DSTB with good effectiveness and less toxicity is crucial for the elimination of TB. Repurposed drug like rifapentine , linezolid , clofazimine , high dose rifampicin , new generation fluoroquinolnes and new developed drug like bedaquiline , pretomanid and demlamanid make the dream come true. How to design short course regimen from animal study to clinical implementation is very interesting topics and helpful for the TB clinicians.

Date: Sunday, April 28, 2024 | Time: 14:50-16:20 (GMT+8)

Moderator: Dr. Ruay-Ming Huang (Taiwan) | Prof. Nicholas Paton (Singapore)

Time (GMT+8)	Topic	Speaker	Country / Region
14:50-15:20	Rifapentine-based short course anti-tuberculosis therapy for drug susceptible tuberculosis and Taiwan experience	Dr. Chin-Chung Shu	Taiwan
15:20-15:50	The role of high dose rifampicin, linezolid, clofazimine in the short course regimen for drug susceptible tuberculosis and Korea experience	Prof. Nakwon Kwak	South Korea
15:50-16:20	Incorporating newer drugs into regimens for treatment of drug-susceptible TB	Prof. Nicholas Paton	Singapore

Rifapentine-based short course anti-tuberculosis therapy for drug susceptible tuberculosis and Taiwan experience

Abstract:
Tuberculosis (TB) remains one of the most prevalent infectious diseases in the world. Currently, for drug-susceptible TB (DS-TB), a standard multi-drug combination therapy lasting at least six months is still required. Although the cure rate for this treatment regimen is high, the prolonged use of medication and the associated treatment costs are significant concerns.

In the past, experts have been working towards shortening the duration of DS-TB treatment, aiming to reduce it to four months. However, previous efforts such as the REMox and RIFAQUIN Trials have ended in failure. Recently, a study investigated the efficacy of daily high-dose rifapentine combined with moxifloxacin, isoniazid, and pyrazinamide over a four-month course. This treatment approach demonstrated non-inferiority compared to the traditional six-month regimen, offering a breakthrough and a new hope for shortening the duration of DS-TB treatment.

In the past-three years, we also conducted a short-course pilot study using high-dose rifapentine combined with moxifloxacin, isoniazid, and pyrazinamide for DS-TB patients in Taiwan. Although the drop out rate is not low but the efficacy seems similar compared with the traditional six-month regimen. We will present the benefits and difficulties in applying the new short-course high dose rifapentine-base treatment for DS-TB in the APRC 2024.

Dr. Chin-Chung Shu

Doctor | National Taiwan University Hospital
Taiwan

Professional Experience:

I am a pulmonologist in National Taiwan University Hospital. Our team is interested in TB/LTBI/NTM lung disease care and research.

The role of high dose rifampicin, linezolid, clofazimine in the short course regimen for drug susceptible tuberculosis and Korea experience

Abstract:
In the search for more effective treatment regimens for drug-susceptible tuberculosis (DS-TB), we will review the potential role of high-dose rifampicin, linezolid, and clofazimine based on our clinical experience in South Korea.

The conventional dose of rifampicin is limited to 10 mg/kg. However, there is increasing evidence that doses of 20 to 30 mg/kg are safe. As a result, attempts have been made to increase the efficacy of rifampicin by increasing the dose. A trial was initiated in South Korea to compare a shorter regimen of 30 mg/kg rifampicin given for 3 months after culture conversion with the standard 6-month HRZE regimen. Although the study was discontinued, it provided valuable insights into the safety and efficacy of high-dose rifampicin.

Linezolid, a cornerstone of multidrug-resistant TB (MDR-TB) treatment, has been widely used. Building on promising evidence of its efficacy, a Korean study compared the effect of 2-4 weeks of linezolid replacing 2 months of ethambutol, with comparable culture conversion rates at 8 weeks. The results showed the potential of linezolid to shorten treatment for DS-TB.

Clofazimine, traditionally used for leprosy, has recently emerged as a key drug for MDR-TB. Although not actively used in South Korea, clofazimine is widely used for other mycobacterial infections. We will present insights into its appropriate dosing and efficacy based on our data.

We hope that our clinical experience in South Korea will provide valuable perspectives for the development of regimens aimed at shortening treatment duration in DS-TB.

Prof. Nakwon Kwak

Associate Professor | Seoul National University Hospital
South Korea

Professional Experience:

Nakwon Kwak graduated from Seoul National University College of Medicine and completed his residency and fellowship at Seoul National University Hospital. Since 2019, he has been working as a staff member in the Division of Pulmonary and Critical Care Medicine at Seoul National University Hospital. He primarily focuses on treating patients with pulmonary tuberculosis and non-tuberculous mycobacterial pulmonary diseases and has been actively involved in clinical research related to these two conditions.

Incorporating newer drugs into regimens for treatment of drug-susceptible TB

Abstract:
The standard 6-month RHZE regimen for drug-susceptible tuberculosis (DS-TB) achieves a very high cure rate in clinical trials, but challenges with adherence and sub-optimal safety and tolerability lead to higher rates of failure and promotion of drug resistance in programme settings. There is increasing optimism that we can find new regimens for DS-TB that may perform better in programme settings. Consideration of the optimal characteristics of a new regimen within the framework of a target regimen profile indicates a number ofpotential areas for improvement – not only in finding regimens of shorter duration than 6 months, but also in enhancing safety, tolerability and other factors that may improve outcomes. An important consideration is the need for trade-offs between desired characteristics until we discover a near-perfect regimen (if ever).

In this talk I will explore the possibly of using bedaquilineas an anchor drug for regimens for DS-TB. I will present data from the TRUNCATE-TB trial that used a 5-drug regimen containing bedaquiline for an initial duration of 8-weeks as part of a treatment strategy; and from the SimpliciTB trial that used bedaquilineas part of a 4-drug regimen given for 16 weeks’ treatment. The talk will look at the potential benefits that bedaquiline might bring to regimens for DS-TB as well as the potential risks. I will also outline some of the ongoing innovative trials in DS-TB that are developing new bedaquiline-containing regimens.

Prof. Nicholas Paton

Professor Of Medicine | National University Of Singapore
Singapore

Professional Experience:

Nicholas Paton is an infectious disease physician and clinical trialist. He trained in medicine and infectious diseases in Cambridge, Sydney and London, and in epidemiology at the London School of Hygiene and Tropical Medicine. He holds joint appointments as Professor of Infectious Diseases at the National University of Singapore and at London School of Hygiene and Tropical Medicine.

His research interests are optimisation of HIV and tuberculosis treatment in resource-limited settings. He leads a programme of tuberculosis treatment trials coordinated from NUS focused on trials of host-directed therapies for tuberculosis; and is the Chief Investigator for the TRUNCATE-TB trial, a trial conducted in a network of 18 sites in Asia and Africa. He is also the Chief Investigator for the flagship trial of the UNITE4TB network – the PARADIGM4TB trial – which is testing multiple new drug combinations for tuberculosis a global network of clinical research sites.

Dr. Ruay-Ming Huang

Pulmonologist | Chest Hospital,Ministry of Health and Welfare
Taiwan

Professional Experience:

Dr. Huang has contributed to Taiwan’s tuberculosis prevention and medical volunteer training for nearly 40 years. In terms of teaching, since 1998, he has been commissioned by the Tuberculosis Prevention Association and the Department of CDC l to train Vietnamese and Mongolian doctors to come to Taiwan to conduct tuberculosis prevention and treatment as well as medical visits and exchanges.

Symposium 20：Programmatic Management of DSTB: Progress and Challenges

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