Details

Autor(en) / Beteiligte

• Rodriguez, Carly A
• Lodi, Sara
• Horsburgh, C Robert
• Mitnick, Carole D
• Bastard, Mathieu
• Huerga, Helena
• Khan, Uzma
• Rich, Michael
• Seung, Kwonjune J
• Atwood, Sidney
• Manzur-Ul-Alam, Md
• Melikyan, Nara
• Mpinda, Stephanie
• Myint, Zaw
• Naidoo, Yugandran
• Petrosyan, Ofelya
• Salahuddin, Naseem
• Sarfaraz, Samreen
• Vilbrun, Stalz Charles
• Yae, Kalkidan
• Achar, Jay
• Ahmed, Saman
• Algozhina, Elena
• Beauchamp, Jude
• de Guadelupe Perea Moreno, Sara
• Gulanbaeva, Munara
• Gergedava, Marika
• Indah Sari, Cut Yulia
• Hewison, Catherine
• Khan, Palwasha
• Franke, Molly F
• Vashist, Atul

Titel

Comparative effectiveness of adding delamanid to a multidrug-resistant tuberculosis regimen comprised of three drugs likely to be effective

Ist Teil von

• PLOS global public health, 2023, Vol.3 (4), p.e0000818

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2023

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Clarity about the role of delamanid in longer regimens for multidrug-resistant TB is needed after discordant Phase IIb and Phase III randomized controlled trial results. The Phase IIb trial found that the addition of delamanid to a background regimen hastened culture conversion; the results of the Phase III trial were equivocal. We evaluated the effect of adding delamanid for 24 weeks to three-drug MDR/RR-TB regimens on two- and six-month culture conversion in the endTB observational study. We used pooled logistic regression to estimate the observational analogue of the intention-to-treat effect (aITT) adjusting for baseline confounders and to estimate the observational analogue of the per-protocol effect (aPP) using inverse probability of censoring weighting to control for time-varying confounding. At treatment initiation, 362 patients received three likely effective drugs (delamanid-free) or three likely effective drugs plus delamanid (delamanid-containing). Over 80% of patients received two to three Group A drugs (bedaquiline, linezolid, moxifloxacin/levofloxacin) in their regimen. We found no evidence the addition of delamanid to a three-drug regimen increased two-month (aITT relative risk: 0.90 (95% CI: 0.73-1.11), aPP relative risk: 0.89 (95% CI: 0.66-1.21)) or six-month culture conversion (aITT relative risk: 0.94 (95% CI: 0.84, 1.02), aPP relative risk: 0.93 (95% CI: 0.83, 1.04)). In regimens containing combinations of three likely effective, highly active anti-TB drugs the addition of delamanid had no discernible effect on culture conversion at two or six months. As the standard of care for MDR/RR-TB treatment becomes more potent, it may become increasingly difficult to detect the benefit of adding a single agent to standard of care MDR/RR-TB regimens. Novel approaches like those implemented may help account for background regimens and establish effectiveness of new chemical entities.