Bedaquiline-based
regimens are associated with large reductions in mortality in people with
drug-resistant tuberculosis, according to research conducted in South Africa
and published in The Lancet Respiratory Medicine.
Compared to standard regimens, use of bedaquiline reduced the
risk of all cause mortality by 75% in people with extensively drug-resistant
tuberculosis (XDR-TB) and by 65% for people with rifampicin-resistant or
multidrug-resistant tuberculosis (MDR-TB)
“The results are
striking and suggest that under field conditions, use of bedaquiline within a
rifampicin-resistant tuberculosis treatment regimen might be associated with a
lower risk of death,” write the authors of an editorial comment. “The recent
decision by the South African National Tuberculosis Program to offer
bedaquiline to most people diagnosed with rifampicin-resistant tuberculosis in
place of injectable drugs rings as a call to action.”
Drug-resistant
tuberculosis is a global health crisis. In 2016, an estimated 600,000 cases of
rifampicin-resistant tuberculosis were diagnosed and there were 190,000 deaths
due to multidrug-resistant tuberculosis. Treatment of MDR- and XDR-TB is
successful in only 54% and 30% of cases, respectively, and the presence of resistance
is associated with high mortality rates.
In 2012, the Food
and Drug Administration in the United States approved bedaquiline for the
treatment of rifampicin-resistant tuberculosis. The drug showed high levels of
efficacy in clinical trials. However, uptake has been sluggish because a phase
2 study suggested that its use was associated with an increased risk of
mortality, possibly due to its side-effects. World Health Organization (WHO) guidelines recommend the use
of bedaquiline only when there is rifampicin resistance, the patient is not
eligible for standard rifampicin-resistant tuberculosis therapy, or the patient
has no other treatment options.
South Africa has a
high burden of tuberculosis, with many cases categorised as MDR- or XDR-TB.
Starting in 2013, access to bedaquiline was provided to people with XDR-TB
and in 2014 the drug was approved for the treatment of MDR-TB. In 2015, the
South African National Tuberculosis Programme started rolling out bedaquiline
as an additional drug to strengthen existing regimens for the therapy of
rifampicin-resistant tuberculosis.
Investigators
undertook a retrospective study comparing mortality rates and risk among
people with XDR- and rifampicin-resistant and MDR-TB, according to whether
their regimens included bedaquiline.
They identified
19,617 adults treated for drug-resistant tuberculosis between mid 2014
and early 2016. The median age was 36
years. Approximately three-quarters were HIV-positive and 63% of the people
with HIV were taking antiretroviral therapy. XDR-TB was diagnosed in 6% of people and rifampicin-resistant
or MDR-TB in 94% of individuals.
Treatment outcomes
were available for 87% of people.
A cure or
completion of treatment was reported for 42%. Sixteen per cent were lost to
follow-up, 4% were reported as failing treatment and 21% were reported to have
died.
Overall, 13% of
people treated with bedaquiline died compared to 25% of those who did not
receive this drug (p < 0.0001).
In people with
XDR-TB, the mortality rate was 15% among those treated with bedaquiline,
almost three times lower than the rate observed among people who received
standard regimens (40%).
For people with
rifampicin-resistant or MDR-TB the mortality rate was 12% among those who
received bedaquiline and 24% for individuals who received alternative therapies.
The authors calculated
that for people with XDR-TB, treatment with bedaquiline was associated with
an almost fourfold reduction in mortality risk (HR = 0.26; 95% CI, 0.07-0.91),
and use of the drug was also associated with a substantial reduction in
mortality risk for people with rifampicin-resistant and MDR-TB (HR = 0.35;
95% CI, 0.024-0.49).
These reductions
in mortality risk were little altered when HIV-infection status and degree of
tuberculosis drug resistance were taken into account.
“Treatment with
bedaquiline was associated with a 3 times reduction in mortality for patients
with multidrug-resistant or rifampicin-resistant tuberculosis and an even
larger reduction in mortality for patients with extensively drug-resistant
tuberculosis,” conclude the authors. “Our results justify consideration of
revised recommendations from WHO and wider use of bedaquiline in
multidrug-resistant, and extensively drug-resistant tuberculosis treatment.”