Delamanid improves outcomes and reduces mortality in multidrug-resistant tuberculosis

Abstract

Multidrug-resistant and extensively drug-resistant tuberculosis (TB) are associated with worse treatment outcomes for patients, including higher mortality, than for drug-sensitive tuberculosis. Delamanid (OPC-67683) is a novel anti-TB medication with demonstrated activity against multidrug-resistant disease.Patients who participated in the previously reported randomised, placebo-controlled trial of delamanid and the subsequent open-label extension trial were eligible to participate in a 24-month observational study designed to capture treatment outcomes. Treatment outcomes, as assessed by clinicians and defined by the World Health Organization, were categorised as favourable and unfavourable. Delamanid treatment groups were combined for analysis, based on their duration of treatment. In total, for 421 (87.5%) out of 481 patients from the original randomised controlled trial, consent was granted for follow-up assessments.Favourable outcomes were observed in 143 (74.5%) out of 192 patients who received delamanid for ≥6 months, compared to 126 (55%) out of 229 patients who received delamanid for ≤2 months. Mortality was reduced to 1.0% among those receiving long-term delamanid versus short-term/no delamanid (8.3%; p<0.001). Treatment benefit was also seen among patients with extensively drug-resistant TB.This analysis suggests that treatment with delamanid for 6 months in combination with an optimised background regimen can improve outcomes and reduce mortality among patients with both multidrug-resistant and extensively drug-resistant TB.

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

“…In a phase 2 randomised controlled trial in patients with MDR tuberculosis, 376 treatment with delamanid resulted in higher rates of culture conversion at 2 months compared with placebo (45·4% vs 29·6%, p=0·008) after 8 weeks of treatment compared with placebo; the The Lancet Respiratory Medicine Commission carry-over observational study 377 showed higher rates of favourable treatment outcome in participants who received 6 months or more versus 2 months or less of delamanid treatment (74·5% vs 55%; p<0·001). 377 Delamanid causes moderate QT prolongation (10-15 ms) but is otherwise well tolerated.…”

“…377 Delamanid causes moderate QT prolongation (10-15 ms) but is otherwise well tolerated. QT prolongation appears to be associated with concentrations of the DM-6705 metabolite.…”

Costs of tuberculosis disease in the European Union: a systematic analysis and cost calculation

“…As it must be recognised, following current trends, Europe is unlikely to achieve elimination of the disease by the target date of 2050 [23,24], we urgently need new vaccines, as well as improved diagnostics [25,26] and new drugs [27][28][29]. With respect to economic considerations, the aim of the present study was to evaluate the costs associated with TB disease in order to determine whether they outweigh the investment needed to generate a new vaccine.…”

Delamanid Does Not Inhibit or Induce Cytochrome P450 Enzymes <i>in Vitro</i>

“…12) Further, delamanid has shown anti-TB activity in patients with drug-sensitive TB 13) and in patients with MDR-TB, and is being specifically developed to treat MDR infections. 14,15) Delamanid has been approved as a new drug for the treatment of MDR-TB and has been launched onto the market in Europe and Japan.…”