Delamanid, an investigational drug to combat tuberculosis, improves outcomes and reduces mortality among patients with the multidrug resistant form of the disease.
Delamanid, an investigational drug to combat tuberculosis, improved outcomes and reduced mortality among patients with the multidrug resistant form of the disease (MDR-TB), researchers reported.
In an observational study, nearly three-quarters of patients who got at least 6 months of treatment with delamanid, combined with an optimized background regimen, had favorable outcomes 2 years later, according to Charles Wells, MD, of Otsuka Pharmaceutical Development and Commercialization in Rockville, Md., and colleagues. The company is developing the agent.
On the other hand, only about half of those who were treated for 2 months or less had a favorable outcome, the researchers reported in the European Respiratory Journal.
Mortality in the long-term treatment group was 1%, compared with 8.3% among those who either got a short course of the drug or placebo.
The analysis is based on two trials of the drug – a randomized blinded trial in 481 patients testing two doses of the drug for 2 months and a 6-month extension of delamanid treatment that involved 213 of the original patients.
In both trials and throughout the observational study period, patients were also on a World Health Organization optimized background regimen.
Over a total of 24 months, the observational study followed the 421 patients from the first trial who agreed to take part with the intention of capturing treatment outcomes, the researchers reported.
For this analysis, treatment outcomes were defined as favorable (cured or completed treatment) or unfavorable (failed, died, or had treatment interrupted for 2 or more months for nonmedical reasons).
Because of the design of the two studies, some patients had between 6 and 8 months of the drug and were defined as the long-term treatment group; those who had 2 months or less of treatment or were on placebo were called the short-term group.
Among the patients in the observational study, 56 had extensively drug resistant TB (XDR-TB).
In the long-term group, Wells and colleagues found little difference between those who had 8 months of treatment and those who had 6; the combined rate of favorable outcomes was 74.5%, including 57.3% who were cured.
On the other hand, the comparable rates in the short-term group were 55% and 48.5%, the researchers found.
The difference in favorable outcomes was significant at P<0.001 and yielded a relative risk of 1.35 (95% CI 1.17 to 1.56).
Among the 56 XDR-TB patients, 44 were in the long-term group, where the rate of favorable outcomes was 61.4%, including a 25% cure rate. Among the 12 in the short-term group, half had a favorable outcome, including 5 cures, or 41.7%.
Overall, two patients died in the long-term group and 19 died in the short-term group – 1% versus 8.3%. The difference led to a relative risk of 0.13 (95% CI 0.03 to 0.53, P<0.001).
Mortality was also lower among those with XDR-TB – there were no deaths in the long-term group and 3 in the short-term group. The difference was also significant at P<0.001.
While the results for XDR-TB patients are "encouraging," the researchers cautioned the sample size was small.
They also noted that there was in some cases up to 4 months delay between ending treatment in the first trial and resuming it in the extension.
The study was sponsored by Otsuka Pharmaceutical Development and Commercialization.
Wells is an employee of the company.
Primary source: European Respiratory Journal
Source reference:
Skripconoka V, et al "Delamanid improves outcomes and reduces mortality for multidrug-resistant tuberculosis" Eur Respir J 2012.
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