Comparative effectiveness of adding delamanid to a multidrug-resistant tuberculosis regimen comprised of three drugs likely to be effective.
| Title: | Comparative effectiveness of adding delamanid to a multidrug-resistant tuberculosis regimen comprised of three drugs likely to be effective. |
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| Authors: | Rodriguez CA; Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, United States of America.; Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.; Lodi S; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America.; Horsburgh CR; Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts, United States of America.; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America.; Department of Global Health, Boston University School of Public Health, Boston, Massachusetts, United States of America.; Department of Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America.; Mitnick CD; Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.; Partners In Health, Boston, Massachusetts, United States of America.; Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.; Bastard M; Epicentre, Paris, France.; Huerga H; Epicentre, Paris, France.; Khan U; Interactive Research and Development Global, Singapore, Singapore.; Rich M; Partners In Health, Boston, Massachusetts, United States of America.; Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.; Seung KJ; Partners In Health, Boston, Massachusetts, United States of America.; Division of Global Health Equity, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.; Atwood S; Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, United States of America.; Manzur-Ul-Alam M; Interactive Research and Development, Dhaka, Bangladesh.; Melikyan N; Epicentre, Paris, France.; Mpinda S; Partners In Health, Maseru, Lesotho.; Myint Z; National Tuberculosis Program, Ministry of Health, Yangon, Myanmar.; Naidoo Y; Interactive Research and Development, Johannesburg, South Africa.; Petrosyan O; Médecins Sans Frontières, Yerevan, Armenia.; Salahuddin N; Indus Hospital & Health Network (IHHN), Karachi, Pakistan.; Sarfaraz S; Indus Hospital & Health Network (IHHN), Karachi, Pakistan.; Vilbrun SC; GHESKIO, Port-au-Prince, Haiti.; Yae K; Partners In Health, Addis Ababa, Ethiopia.; Achar J; Médecins Sans Frontières, United Kingdom.; Ahmed S; Interactive Research and Development, Karachi, Pakistan.; Algozhina E; Partners In Health, Almaty Kazakhstan.; Beauchamp J; Zanmi Lasante, Cange, Haiti.; de Guadelupe Perea Moreno S; Socios En Salud Sucursal, Lima, Peru.; Gulanbaeva M; Médecins Sans Frontières, Osh, Kyrgyzstan.; Gergedava M; Médecins Sans Frontières, Tbilisi, Georgia.; Indah Sari CY; Rumah Sakit Islam Jakarta Cempaka Putih, Jakarta, Indonesia.; Hewison C; Médecins Sans Frontières, Paris, France.; Khan P; Interactive Research and Development Global, Singapore, Singapore.; Franke MF; Department of Global Health and Social Medicine, Harvard Medical School, Boston, Massachusetts, United States of America. |
| Source: | PLOS global public health [PLOS Glob Public Health] 2023 Apr 28; Vol. 3 (4), pp. e0000818. Date of Electronic Publication: 2023 Apr 28 (Print Publication: 2023). |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Public Library of Science Country of Publication: United States NLM ID: 9918283779606676 Publication Model: eCollection Cited Medium: Internet ISSN: 2767-3375 (Electronic) Linking ISSN: 27673375 NLM ISO Abbreviation: PLOS Glob Public Health Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Original Publication: San Francisco, California : Public Library of Science, [2021]- |
| Abstract: | 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.; (Copyright: © 2023 Rodriguez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.) |
| Competing Interests: | The endTB Consortium coordinated donations of delamanid (Otsuka Pharmaceutical) and bedaquiline (Janssen) to be used for treatment by some of the patients included in the endTB Observational Study. All authors report no additional potential conflicts of interest. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials. |
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| Grant Information: | F31 AI157333 United States AI NIAID NIH HHS; R01 AI146095 United States AI NIAID NIH HHS |
| Entry Date(s): | Date Created: 20230428 Latest Revision: 20240917 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC10146539 |
| DOI: | 10.1371/journal.pgph.0000818 |
| PMID: | 37115740 |
| Database: | MEDLINE |
Journal Article