Novel treatment for drug-resistant tuberculosis shows promise, but concerns for patient safety remain

July 11, 2014, Lancet

In a viewpoint published this week in The Lancet, the Community Research Advisors Group (CRAG) argue that research into bedaquiline – a new drug, fast tracked for multidrug-resistant tuberculosis (MDR-TB) – should proceed cautiously in people with drug-sensitive tuberculosis. CRAG, an international, community-based advisory board for the US Centers for Disease Control and Prevention's Tuberculosis Trials Consortium, writing in The Lancet independently, urge researchers to balance the goal of shortening treatment for drug-sensitive TB with patient safety.

Bedaquiline is the first novel drug to be approved for treatment of tuberculosis in forty years. The FDA fast-tracked the approval of the drug after phase 2 studies showed bedaquiline's promising activity against MDR-TB (the drug reduced the average time to a negative TB culture from 18 to 12 weeks, and increased the proportion of participants with a negative culture at 6 months from 58% to 79%). Current treatments for drug-resistant tuberculosis show improved outcomes when continued for 18 to 24 months, and even then cure rates range from 11% to 79% depending on the extent of resistance. This presents a huge burden both on health care facilities and on patients to stick to a strict, toxic, and lengthy regimen, often in settings where available resources and cost make long drug treatments difficult to implement.

However, along with the potential benefits of bedaquiline, the authors point out that the drug presents several safety concerns that should be addressed before testing the drug in people with drug-sensitive TB, who already have a very effective treatment option and as such face different risk-benefit considerations than people with drug-resistant TB. In one phase 2 trial, a significantly higher number of participants receiving bedaquiline died than those receiving placebo. The majority of these deaths had no common cause and occurred months after the trial ended, but due to the long half-life of the drug, adverse effects from the drug cannot be ruled out. Close follow-up monitoring is needed due to an increased rate of liver and cardiac toxicity observed in patients receiving bedaquiline, say the authors.

The authors also call on the drug's developer, Janssen, to make information regarding the drug's safety available to public research groups, and to immediately begin trials on the effects of the drug in populations that use alcohol and drugs, and that have Hepatitis B and C. These groups could both benefit greatly from future shortened tuberculosis treatment regimens, but are also at a greater risk of some of the drug's reported side effects.

According to CRAG co-chair Dorothy Namutamba, "Although up to this point it has only been studied as an addition to existing regimens for drug-resistant tuberculosis, bedaquiline shows a lot of promise for improving treatment in the future. However, the drug also shows potentially serious adverse effects ranging from liver toxicity, disruption of the heart's electrical rhythm, and even death. As trials of this novel drug are considered in patients with drug-sensitive , researchers need to carefully balance the potential benefit of the new while making sure to always place the safety of the trial participants at the forefront of any considerations."

Explore further: J&J seeks OK for first drug against resistant TB

Related Stories

J&J seeks OK for first drug against resistant TB

July 2, 2012
(AP) — Johnson & Johnson said Monday that it is seeking U.S. approval for the first new type of medicine to fight deadly tuberculosis in more than four decades.

Scientists establish proof-of-concept for host-directed tuberculosis therapy

June 27, 2014
In a new study published in Nature, scientists describe a new type of tuberculosis (TB) treatment that involves manipulating the body's response to TB bacteria rather than targeting the bacteria themselves, a concept called ...

Drug resistance-associated genes: A cornerstone for the control and protection against tuberculosis

September 5, 2013
BGI in collaboration with Institute of Biophysics, Chinese Academy of Sciences, and other Chinese institutes, have completed the genome sequencing of 161 Mycobacterium tuberculosis that can cause an infectious disease tuberculosis ...

New consensus reached to help tackle multidrug-resistant and extensively drug-resistant TB

March 23, 2014
New consensus statements have been developed to help tackle the growing threat of multidrug-resistant tuberculosis (TB) and extensively drug-resistant tuberculosis (TB).

Potential new drug for tuberculosis

August 5, 2013
A new drug capable of inhibiting growth of Mycobacterium tuberculosis is reported this week in Nature Medicine. The findings may improve therapeutic options for the treatment of drug resistant tuberculosis (TB).

Recommended for you

New long-acting approach for malaria therapy developed

January 22, 2018
A new study, published in Nature Communications, conducted by the University of Liverpool and the Johns Hopkins University School of Medicine highlights a new 'long acting' medicine for the prevention of malaria.

Virus shown to be likely cause of mystery polio-like illness

January 22, 2018
A major review by UNSW researchers has identified strong evidence that a virus called Enterovirus D68 is the cause of a mystery polio-like illness that has paralysed children in the US, Canada and Europe.

Creation of synthetic horsepox virus could lead to more effective smallpox vaccine

January 19, 2018
UAlberta researchers created a new synthetic virus that could lead to the development of a more effective vaccine against smallpox. The discovery demonstrates how techniques based on the use of synthetic DNA can be used to ...

Study ends debate over role of steroids in treating septic shock

January 19, 2018
The results from the largest ever study of septic shock could improve treatment for critically ill patients and save health systems worldwide hundreds of millions of dollars each year.

New approach could help curtail hospitalizations due to influenza infection

January 18, 2018
More than 700,000 Americans were hospitalized due to illnesses associated with the seasonal flu during the 2014-15 flu season, according to federal estimates. A radical new approach to vaccine development at UCLA may help ...

Flu may be spread just by breathing, new study shows; coughing and sneezing not required

January 18, 2018
It is easier to spread the influenza virus (flu) than previously thought, according to a new University of Maryland-led study released today. People commonly believe that they can catch the flu by exposure to droplets from ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.