Will advances in TB treatment outweigh the COVID-19 pushback ?
Shobha Shukla - CNS
The impact of the COVID-19 pandemic on TB diagnosis and mortality in 2020 has been frightening, to say the least. Recently released WHO data shows that 1.4 million fewer people got TB care in 2020 as compared to 2019- a 21% decrease. Also over 0.5 million people died from TB in 2020 due to lack of diagnosis.
Latest data by Stop TB Partnership shows that in 9 countries (Bangladesh, India, Indonesia, Myanmar, Pakistan, Philippines, South Africa, Tajikistan, and Ukraine) which together account for 60% of the global TB burden, TB diagnosis and treatment enrolment in 2020 declined by 1 million - a drastic reduction of 23%.
Globally, in 2020 there was an estimated drop of at least 1 million in TB treatment enrolment, pushing the TB response to 2008 levels in terms of people diagnosed and treated.
A modelling analysis done in May 2020 found that even short COVID-19 related lockdowns can generate long-lasting setbacks in TB control, due to disruption in routine TB care services. A 3-month lockdown followed by 10-months to restore to normal could lead to an additional 6.3 million cases of TB and an additional 1.4 million TB deaths between 2020 and 2025 globally. In India the disruptions are expected to cause an additional 1.19 million TB cases and 361,000 TB deaths over the next 5 years.
However, while the TB care and control situation is very grim, it is not a lost cause. Even amid the global pandemic, TB treatment innovations have advanced at an unprecedented pace, thanks to the untiring efforts of our scientific community. Encouraging results from some phase-3 clinical studies of new drug regimens provide the much needed hope of better and more patient-friendly treatments for drug-susceptible as well as drug-resistant TB.
Shorter and all oral regimen for XDR and MDR-TB
At CROI 2021, Dr Pauline Howell of the University of the Witwatersrand, South Africa, presented a new analysis based on two years of the Nix-TB study, in which approximately 90% of the patients with highly drug-resistant TB who were treated with a 6-month, all-oral regimen of pretomanid, bedaquiline and linezolid (BPaL) remained free of their disease. Pretomanid, which is used in this regimen, is a new chemical entity developed by TB Alliance.
Nix-TB is an open-label, single-group study that had 65% participants with XDR-TB and 35% patients with unresponsive MDR-TB. At 6 months after the completion of therapy, 90% of the enrolled patients were found to have had a favourable outcome - 89% of those with XDR-TB and 92% of those with MDR-TB.
The study thus shows that XDR-TB and complicated MDR-TB can be treated with a 26 week long all oral 3 drug regimen with a 90% success rate, which is similar to that obtained with the standard of care in the treatment for drug-sensitive TB. Currently used regimens have had a success cure rate of only 34% for XDR-TB and 55% for MDR-TB cases.
Moreover, they routinely last for two years or longer and are very costly.
In her presentation at CROI, Dr Howell shared that, "Results of this simplified, shortened, and all-oral regimen for highly drug-resistant TB show sustained high efficacy through a 2-year follow-up from end of treatment. A follow-on trial ZeNix that investigates the optimal dose and duration of linezolid in the BPaL regimen, has recently completed enrolment.
The objective of this study is to evaluate if the efficacy of the BPaL drug regimen can be maintained, while reducing toxicity and increasing tolerability through a shorter linezolid duration of 2 months and/or its smaller dose of 600 mg (as compared to the current 1200 mg dosage). We look forward to the primary endpoint 6 months into post treatment results."
Meanwhile, WHO has recommended the BPaL regimen under operational research conditions and it has also been authorised by the European Medicines Agency.
In an exclusive interview given to CNS (Citizen News Service), Dr Howell said, "TB Alliance is studying this regimen in multiple countries. Operational research is now underway in at least 5 countries with many more expected to join this year. Physicians in USA are prescribing the regimen under routine practice conditions. The regimen was approved in India by the Drug Controller General of India (DCGI) last year.
The ZeNix trial is taking place in Russia, Georgia, Moldova and South Africa, evaluating different doses and durations of the drug linezolid as part of this regimen. They have also partnered with MSF to evaluate BPaL-based regimens for all people with DR-TB (at least rifampicin-resistant TB), and not just highly drug-resistant strains."
(To be contd)