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.

Keywords: Extensively drug-resistant; mycobacterium; pulmonary infection; treatment outcomes.

Figure 1–

World Health Organization (WHO) recommended treatment for multidrug-resistant tuberculosis (MDR-TB) and the design of delamanid Trial 204, Trial 208 and Study 116. a) WHO optimised background treatment regimen (OBR) recommendations for the treatment of MDR-TB [19]. b) Otsuka (Otsuka, Tokyo, Japan) design for Trial 204, Trial 208 and Study 116 (delamanid trials/study). SCC: sputum culture conversion. ^#: time varied between the completion of Trial 204 and the initiation of Trial 208 based on local approval processes.

Figure 2–

Flowchart of intent-to-treat patients in delamanid (DLM) Trial 204, Trial 208 and Study 116. ^#: patients who did not participate in Trial 208 were eligible for participation in Study 116 following their completion of Trial 204; ^¶: time between the completion of Trial 204 and the initiation of Trial 208 was variable and was based on local approval processes.