Combining the investigational drug delamanid with standard tuberculosis treatment significantly increased sputum-culture conversion rates in MDR tuberculosis, an international study demonstrated.
The results could be particularly good news for China, which now has one-quarter of the world’s cases of MDR TB, according to a second study.
In the delamanid study, the conversion proportion was 45% after 2 months of treatment among those who received the new drug plus standard therapy, compared with a 30% rate for standard therapy alone, Dr. Maria T. Gler and her coauthors reported in the June 7 issue of the New England Journal of Medicine.
"It is important to learn more about the use of delamanid in combination with other new and existing antimycobacterial agents to develop better regimens for multidrug-resistant tuberculosis," wrote Dr. Gler, of Makati Medical Center and the Tropical Disease Foundation, Makati City, Philippines, and her colleagues (N. Engl. J. Med. 2012;366:2151-60).
Delamanid, which inhibits mycolic acid synthesis, has shown effectiveness against drug-susceptible and drug-resistant strains of Mycobacterium tuberculosis in preclinical tests.
The team investigated the drug’s effect at 200 mg/day and 400 mg/day, plus a background treatment regimen approved by the World Health Organization for multidrug-resistant (MDR) tuberculosis. A placebo group received only the background treatment – the current standard of care. The 2-month study was carried out in nine countries: China, Egypt, Estonia, Japan, Korea, Latvia, Peru, the Philippines, and the United States.
The study group included 481 patients with sputum culture–proven MDR tuberculosis infections. The patients’ mean age was 35 years. More than 90% of the group had received prior treatment for tuberculosis, including 50% who had already taken only first-line antitubercular agents and 40% who had received a second- or third-line agent. Only four of the patients were coinfected with HIV.
By the end of 2 months, both groups receiving delamanid had significantly higher proportions of sputum-culture conversion than the placebo groups. Similar conversion proportions occurred in both active groups: 45% of the 200-mg/day delamanid group, and 42% of the 400-mg/day group. Conversion in the placebo group (30%) was significantly less than in both of the active groups.
Time to conversion also differed significantly between the active and placebo groups, with conversion proportions beginning to separate by 30 days of treatment.
There were more adverse events in the delamanid groups, although the investigators found that only the incidence of QT prolongation was significantly less in the placebo group (4%) than in the 200- and 400-mg/day delamanid groups (10% and 13%, respectively). None of the arrhythmias were clinically significant, they noted.
There were no between-group differences in the rate of hepatotoxicity. One patient died from tuberculosis during the trial.
A longer trial is underway to more closely examine delamanid’s effect on the hard-to-treat disease in patients taking antiretroviral drugs for HIV infections.