WHO maintains existing recommendations for the use of bedaquiline
The conditional recommendation will be maintained until a new systematic review of evidence is warranted or the results of the phase III clinical trial of bedaquiline become available.
Geneva ¦ 13 March 2017 - Three years after the issuance of the interim policy guidance on the use of bedaquiline in the treatment of multidrug-resistant tuberculosis (MDR-TB), the World Health Organization (WHO) convened a Guideline Development Group meeting to assess new evidence and experiences of countries in implementing bedaquiline. Following the evidence assessment made by the Guideline Development Group, the experts advised WHO to prolong the existing conditional recommendation on the use of bedaquiline to strengthen the longer MDR-TB regimens in line with the latest WHO guidelines on the treatment of drug-resistant TB. The conditional recommendation will be maintained until a new systematic review of evidence is warranted or the results of the phase III clinical trial become available.
The decision was based on an extensive evaluation undertaken by
the Guideline Development Group, with review of data from 537
patients. The data set included patients enrolled from Armenia,
France, Georgia, South Africa, as well as data provided by the
drug manufacturer, Janssen Pharmaceuticals, from 11
countries.
“New anti-tuberculosis drugs such as
bedaquiline represent a major advance in the management of
MDR-TB patients. We have gone from having very limited
alternatives to treat MDR- and XDR-TB to having now two new
drugs which offer hope to patients. WHO recommendations on their
use, given accelerated regulatory approval after phase IIb
trials, must be based on well-documented evidence of efficacy
and lack of toxicity”, said Dr Mario Raviglione, Director
of the WHO Global TB Programme. “WHO looks forward to
reviewing results from Phase III trials as soon as available,
which could potentially expand use of this drug, saving more
lives.”
In line with the existing WHO
conditional recommendation on bedaquiline, countries are
encouraged to continue using bedaquiline in patients who are not
eligible for the shorter MDR-TB regimen and who have: i)
confirmed additional resistance to fluoroquinolones (MDR-TB+FQ)
or second-line injectable drugs (MDR-TB+SLI); ii) confirmed
extensively drug-resistant TB (XDR-TB); iii) known adverse drug
reactions, poor tolerance, or contraindication to any component
of the combination regimen; or iv) in cases of unavailability or
lack of guaranteed supply of a medicine being part of the
combination regimen. In practice, this means that virtually all
the MDR-TB patients not eligible to receive the shorter MDR-TB
regimen may be eligible to receive a regimen that includes
bedaquiline.
Although the observational data assessed
by the Guideline Development Group were suggestive of a
reduction in mortality for patients using bedaquiline in
combination with a WHO-recommended longer regimen,
specific harms (e.g. adverse events such as cardio-toxicity)
were similar to those observed in the original phase IIb
randomised control trial. WHO therefore continues to recommend
active TB drug-safety monitoring and management (aDSM) of all
patients receiving treatment with bedaquiline to identify and
manage any adverse event as early as possible. The
implementation of aDSM is not only helpful for the systematic
monitoring and management of patient safety, but can also help
support the scale-up of bedaquiline, delamanid and shorter
treatment regimens within countries, and ultimately help policy
refinement at local and global levels in the future.
“We
need systematic monitoring of all patients receiving the drugs
according to established conditions. Regular patient and
treatment monitoring facilitate the early identification of
at-risk patients and provide an opportunity for clinicians and
health services to respond in a timely manner and prevent
complications,” said Dr Karin Weyer, Coordinator,
Laboratories, Diagnostics & Drug-Resistance, WHO Global TB
Programme. “It is therefore essential that the
implementation of new drugs goes hand-in-hand with close
clinical and laboratory monitoring of patients.”
For
more information on the WHO evaluation process on the use of
bedaquiline within the wider framework of recommendations for
the management of drug-resistant TB, please find below a
Frequently Asked Questions (FAQ) sheet, developed by WHO with
technical and implementing partners and other stakeholders.
