title: 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.
authors.affiliation: Riga East University Hospital, Centre of Tuberculosis and Lung Diseases, Riga, Latvia.
authors.forename: Vija
authors.initials: V
authors.lastname: Skripconoka
authors.forename: Manfred
authors.initials: M
authors.lastname: Danilovits
authors.forename: Lea
authors.initials: L
authors.lastname: Pehme
authors.forename: Tarmo
authors.initials: T
authors.lastname: Tomson
authors.forename: Girts
authors.initials: G
authors.lastname: Skenders
authors.forename: Tiina
authors.initials: T
authors.lastname: Kummik
authors.forename: Andra
authors.initials: A
authors.lastname: Cirule
authors.forename: Vaira
authors.initials: V
authors.lastname: Leimane
authors.forename: Anu
authors.initials: A
authors.lastname: Kurve
authors.forename: Klavdia
authors.initials: K
authors.lastname: Levina
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Geiter
authors.forename: Davide
authors.initials: D
authors.lastname: Manissero
authors.forename: Charles D
authors.initials: CD
authors.lastname: Wells
mesh_terms: D000293:Adolescent; D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D054908:Extensively Drug-Resistant Tuberculosis / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009593:Nitroimidazoles / Q000627:therapeutic use*; D010080:Oxazoles / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000401:mortality; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D009593:Nitroimidazoles; C516022:OPC-67683; D010080:Oxazoles