Tuberculosis

Adding Delamanid to Combination Regimen Reduces Risk of Death for People with Resistant TB

The novel investigational tuberculosis (TB) drug delamanid, when added to an optimized combination regimen, significantly reduced mortality among patients with multidrug-resistant TB, according to a study published in the September 27, 2012, advance edition of the European Respiratory Journal.

Tuberculosis remains a leading cause of illness and death worldwide. Recent years have seen increased reports of multidrug-resistant Mycobacterium tuberculosis (MDR-TB), which does not respond to standard first-line medications, and extensively drug-resistant TB (XDR-TB), which is resistant to most or all available therapies.

Delamanid (OPC-67683), under development by Japan's Otsuka Pharmaceutical Co., is a nitro-dihydro-imidazooxazole derivative that inhibits synthesis of mycolic acid, an important component of TB bacteria cell walls.

As previously reported, a Phase 2b trial compared delamanid (100 mg or 200 mg twice-daily) vs placebo, both in combination with a World Health Organization-recommended background regimen, which typically consists of 4-5 other drugs. The study demonstrated that delamanid was active against highly-resistant TB, clearing infection in more than 40% of patients.

Vija Skripconoka from Riga East University Hospital in Latvia and colleagues looked at longer-term outcomes among patients who participated in the randomized trial and a subsequent open-label extension study. The delamanid dose arms were combined for analysis according to duration of treatment. This observational study continued for 24 months, with outcomes categorized as "favorable" or "unfavorable."

Results

• 421 of the 481 patients (87.5%) in the original randomized controlled trial were followed and assessed in the observational study.
• 143 patients (74.5%) who received delamanid for at least 6 months achieved favorable outcomes, compared with 126 patients (55.0%) who received delamanid for less than 2 months.
• Mortalitywas reduced to 1.0% among participants who received long-term delamanid, compared with 8.3% among those who received short-term or no delamanid.
• A treatment benefit was also seen among patients with XDR-TB.

This analysis, the researchers concluded, "suggests that treatment with delamanid for 6 months in combination with an optimized background regimen can improve outcomes and reduce mortality among patients with both multidrug-resistant and extensively drug-resistant tuberculosis."

10/10/12

Reference

V Skripconoka, M Danilovits, L Pehme, et al. Delamanid Improves Outcomes and Reduces Mortality for Multidrug-Resistant Tuberculosis. European Respiratory Journal. September 27, 2012 (Epub ahead of print).