Promise with new triple drug combo for resistant TB

Infectious diseases

By Mardi Chapman

10 Mar 2020

A new triple therapy for extensively drug-resistant (XDR) tuberculosis and complicated forms of multidrug-resistant (MDR) tuberculosis may replace the multi-drug regimens currently in use and offers some promise in the race to meet WHO End TB goals. 

An open-label, single-group study across three sites in South Africa has found the all-oral combination of bedaquiline, pretomanid and linezolid resulted in a favourable outcome in 90% of participants within six months.

The study group were 109 people with a median age of 35 years, who had lived with TB for a median of 12 months, and had received a median of seven drugs for their hard to treat TB in the previous month. About half the group (51%) were also HIV positive. 

Patients received 400 mg bedaquiline once daily for 2 weeks followed by 200 mg three times a week for 24 weeks; 200 mg pretomanid daily for 26 weeks and 1200 mg linezolid daily for up to 26 weeks (with dose adjustment for toxic effects).

The study found a favourable outcome – resolution of clinical TB or negative culture at six months after the end of therapy – in 89% of XDR patients and 92% of MDR patients. 

However there were adverse events including mostly mild to moderate peripheral neuropathy in 81% of patients and haematologic toxic effects such as myelosuppression in 48% of patients.

Patients will be followed up again as 12-months post-treatment.

An editorial, also in NEJM, said cure rates for XDR tuberculosis were less than 50% before the advent of new drugs.

“Therefore, this is a triumph, and the authors are to be congratulated for their vision and courage in tackling the most difficult-to-treat forms of tuberculosis.”

The editorial said the public health tragedy was “the overlapping realities of the persisting need for new regimens and the spectacular inadequacy of support for their development and the tools needed for their effective use in the field.”

In particular, they said the development of accessible and affordable laboratory tools for the detection of drug resistance to previous treatment regimens had not been prioritised.

And, unfortunately, “…resistance is also a risk for the bedaquiline–pretomanid–linezolid regimen.”  

Along with continued investment in worldwide detection and monitoring of TB drug resistance, they also called for a rejuvenated program of phase 2 and 3 randomised controlled clinical trials of new drugs. 

“Until that happens, if the current inadequate investment path is held, history is bound to repeat itself — and for all the jubilation that comes with developing a new effective regimen, there will be more tragedy yet to come.”

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