Six-Month All-Oral Treatment for MDR/RR-TB: Findings of an ICMR-NIRT Study

A recent study conducted by the National Institute for Research on Tuberculosis (NIRT), under the Indian Council of Medical Research (ICMR), has revealed the important finding that a six-month all-oral treatment for multidrug-resistant and rifampicin-resistant TB (MDR/RR-TB) is not only cost-effective but also provides better health outcomes than long-term treatment regimens prevalent in India.

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¨     The Indian Council of Medical Research, through its ICMR National Institute for Research in Tuberculosis, published an economic evaluation in the Indian Journal of Medical Research assessing shorter regimens for multidrug-resistant and rifampicin-resistant tuberculosis.

¨     The study compared six-month bedaquiline-based regimens, namely BPaL and BPaLM, with the existing nine-to eleven-month and eighteen to twenty-month regimens under the National TB Elimination Programme.

¨     The findings support programmatic adoption of shorter all oral regimens to strengthen India’s response to drug-resistant tuberculosis.

Key Findings of the Study

¨     The BPaL regimen was found to be more effective and cost-saving compared to the standard regimen.

¨     The health system saves ₹379 per patient for every additional Quality Adjusted Life Year gained under the BPaL regimen.

¨     The BPaLM regimen was found to be highly cost-effective with an additional expenditure of only ₹37 per patient per additional Quality Adjusted Life Year gained.

¨     Both regimens were associated with lower or comparable overall healthcare costs, including medicines hospital visits and follow up care.

¨     The reduction of treatment duration from nine to eighteen months to six months improves patient adherence and reduces morbidity.

¨     The findings provide strong economic and public health justification for scaling up shorter regimens under the National TB Elimination Programme.

All-oral regimens for drug-resistant tuberculosis (DR-TB)

¨     The World Health Organisation (WHO) currently recommends three main categories of all-oral regimens for Multi-Drug Resistant/Rifampicin Resistant TB (MDR/RR-TB).

The 6-Month BPaLM/BPaL Regimen

¨     This is the preferred first-line choice for patients aged 14 and older with MDR/RR-TB or pre-extensively drug-resistant TB (pre-XDR-TB). It is significantly shorter than previous standards and has a high treatment success rate (approx. 90%).

¨     BPaLM Components: Bedaquiline (B), Pretomanid (Pa), Linezolid (L), and Moxifloxacin (M).

¨     BPaL Variation: Moxifloxacin is omitted (leaving B, Pa, and L) if the patient has documented resistance to fluoroquinolones.

¨     Duration: Typically 6 months (26 weeks), though it can be extended to 9 months if necessary.

¨     Benefits: Lower pill burden, reduced cost, and improved patient compliance.

9-Month All-Oral Regimens

¨     These are suggested for patients in whom resistance to fluoroquinolones has been excluded and who may not be eligible for the 6-month regimen.

¨     Standard 9-Month Regimen: A combination of seven drugs, including Bedaquiline, Levofloxacin (or Moxifloxacin), Clofazimine, Ethionamide (can be replaced by 2 months of Linezolid), Ethambutol, Pyrazinamide, and High-dose Isoniazid.

¨     Modified 9-Month Regimens (from endTB trial): Recent 2024 updates include variations like BLMZ (Bedaquiline, Linezolid, Moxifloxacin, Pyrazinamide), which is often preferred for its lower cost and pill burden.

Longer Individualised All-Oral Regimens

¨     For patients ineligible for shorter courses—such as those with extensive drug resistance (XDR-TB), severe forms of extrapulmonary TB (e.g., CNS involvement), or intolerance to core drugs—WHO suggests an individualised regimen.

¨     Duration: 18–20 months (or 15–17 months after culture conversion).

¨     Composition: Built using a priority ranking of drugs:

¨     Group A (Strongly Recommended): Levofloxacin/Moxifloxacin, Bedaquiline, and Linezolid.

¨     Group B: Clofazimine, Cycloserine/Terizidone.

¨     Group C: Other agents (e.g., Delamanid, Pyrazinamide, Ethambutol) added as needed to ensure at least 4–5 effective drugs.

Tuberculosis

¨     Tuberculosis (TB) is a bacterial infection caused by bacteria (Mycobacterium tuberculosis) that primarily affects the lungs and spreads through the air when an infected person coughs, sneezes, or spits.

¨     It is preventable and curable with antibiotics such as rifampicin and isoniazid.

¨     TB is the leading cause of death of people with HIV and also a major contributor to antimicrobial resistance (AMR).

¨     The Bacille Calmette-Guérin (BCG) vaccine is given to infants and young children in some countries to prevent severe forms of TB and reduce the risk of death.

¨     Risk factors for developing TB disease include diabetes, weakened immune systems (e.g., HIV/AIDS), malnutrition, tobacco use, and harmful alcohol consumption.

Types of TB conditions

¨     Pulmonary TB: It involves the lungs and is the most common form of TB.

¨     Extrapulmonary TB: It occurs outside the lungs, affecting parts such as the bones, kidneys, spine, brain, and lymph nodes.

¨     Miliary TB: It is a rare but serious form where TB bacteria spread through the bloodstream to multiple organs. It is more common in young children and people with weakened immune systems.

¨     TB Meningitis: It affects the tissue surrounding the brain and spinal cord, often seen at the base of the brain.

¨     Drug-Resistant TB: It occurs when TB bacteria are resistant to the standard medications used to treat the disease.

¨     Drug-Resistant TB: It occurs when TB bacteria are resistant to the standard medications used to treat the disease.