Effectiveness of a bedaquiline, linezolid, clofazimine "core" for multidrug-resistant tuberculosis
Rationale: Treatment outcomes may be compromised among patients with multidrug- or rifampicin-resistant tuberculosis with additional fluoroquinolone resistance. Evidence is needed to inform optimal treatment for these patients.
Objectives: We compared the effectiveness of longer individualized regimens comprised of bedaquiline for 5 to 8 months, linezolid, and clofazimine to those reinforced with at least 1 third-tier drug and/or longer duration of bedaquiline.
Methods: We emulated a target trial to compare the effectiveness of initiating and remaining on the core regimen to one of five regimens reinforced with (1) bedaquiline for ≥9 months, (2) bedaquiline for ≥9 months and delamanid, (3) imipenem, (4) a second-line injectable, or (5) delamanid and imipenem. We included patients in whom a fluoroquinolone was unlikely to be effective based on drug susceptibility testing and/or prior exposure. Our analysis consisted of cloning, censoring, and inverse-probability weighting to estimate the probability of successful treatment.
Measurements and Main Results: Adjusted probabilities of successful treatment were high across regimens, ranging from 0.75 (95%CI:0.61, 0.89) to 0.84 (95%CI:0.76, 0.91). We found no substantial evidence that any of the reinforced regimens improved effectiveness of the core regimen, with ratios of treatment success ranging from 1.01 for regimens reinforced with bedaquiline ≥9 months (95%CI:0.79, 1.28) and bedaquiline ≥9 months plus delamanid (95%CI:0.81, 1.31) to 1.11 for regimens reinforced by a second-line injectable (95%CI:0.92, 1.39) and delamanid and imipenem (95%CI:0.90, 1.41).
Conclusions: High treatment success underscores the effectiveness of regimens comprised of bedaquiline, linezolid, and clofazimine, highlighting the need for expanded access to these drugs.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
medRxiv : the preprint server for health sciences - (2024) vom: 19. Jan. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zeng, Chengbo [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Revised 02.02.2024 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1101/2024.01.18.24301453 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM367834170 |
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| 100 | 1 | |a Zeng, Chengbo |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Effectiveness of a bedaquiline, linezolid, clofazimine "core" for multidrug-resistant tuberculosis |
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| 500 | |a Date Revised 02.02.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Rationale: Treatment outcomes may be compromised among patients with multidrug- or rifampicin-resistant tuberculosis with additional fluoroquinolone resistance. Evidence is needed to inform optimal treatment for these patients | ||
| 520 | |a Objectives: We compared the effectiveness of longer individualized regimens comprised of bedaquiline for 5 to 8 months, linezolid, and clofazimine to those reinforced with at least 1 third-tier drug and/or longer duration of bedaquiline | ||
| 520 | |a Methods: We emulated a target trial to compare the effectiveness of initiating and remaining on the core regimen to one of five regimens reinforced with (1) bedaquiline for ≥9 months, (2) bedaquiline for ≥9 months and delamanid, (3) imipenem, (4) a second-line injectable, or (5) delamanid and imipenem. We included patients in whom a fluoroquinolone was unlikely to be effective based on drug susceptibility testing and/or prior exposure. Our analysis consisted of cloning, censoring, and inverse-probability weighting to estimate the probability of successful treatment | ||
| 520 | |a Measurements and Main Results: Adjusted probabilities of successful treatment were high across regimens, ranging from 0.75 (95%CI:0.61, 0.89) to 0.84 (95%CI:0.76, 0.91). We found no substantial evidence that any of the reinforced regimens improved effectiveness of the core regimen, with ratios of treatment success ranging from 1.01 for regimens reinforced with bedaquiline ≥9 months (95%CI:0.79, 1.28) and bedaquiline ≥9 months plus delamanid (95%CI:0.81, 1.31) to 1.11 for regimens reinforced by a second-line injectable (95%CI:0.92, 1.39) and delamanid and imipenem (95%CI:0.90, 1.41) | ||
| 520 | |a Conclusions: High treatment success underscores the effectiveness of regimens comprised of bedaquiline, linezolid, and clofazimine, highlighting the need for expanded access to these drugs | ||
| 650 | 4 | |a Preprint | |
| 700 | 1 | |a Hernán, Miguel A |e verfasserin |4 aut | |
| 700 | 1 | |a Trevisi, Letizia |e verfasserin |4 aut | |
| 700 | 1 | |a Sauer, Sara |e verfasserin |4 aut | |
| 700 | 1 | |a Mitnick, Carole D |e verfasserin |4 aut | |
| 700 | 1 | |a Hewison, Catherine |e verfasserin |4 aut | |
| 700 | 1 | |a Bastard, Mathieu |e verfasserin |4 aut | |
| 700 | 1 | |a Khan, Palwasha |e verfasserin |4 aut | |
| 700 | 1 | |a Seung, Kwonjune J |e verfasserin |4 aut | |
| 700 | 1 | |a Rich, Michael L |e verfasserin |4 aut | |
| 700 | 1 | |a Law, Stephanie |e verfasserin |4 aut | |
| 700 | 1 | |a Kikvidze, Marina |e verfasserin |4 aut | |
| 700 | 1 | |a Kirakosyan, Ohanna |e verfasserin |4 aut | |
| 700 | 1 | |a Miankou, Alexey |e verfasserin |4 aut | |
| 700 | 1 | |a Thit, Phone |e verfasserin |4 aut | |
| 700 | 1 | |a Mamsa, Shahid |e verfasserin |4 aut | |
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| 700 | 1 | |a Binegdie, Amsalu Bekele |e verfasserin |4 aut | |
| 700 | 1 | |a Temirova, Kulbaram |e verfasserin |4 aut | |
| 700 | 1 | |a Oyewusi, Lawrence |e verfasserin |4 aut | |
| 700 | 1 | |a Philippe, Kerline |e verfasserin |4 aut | |
| 700 | 1 | |a Vilbrun, Stalz C |e verfasserin |4 aut | |
| 700 | 1 | |a Khan, Uzma |e verfasserin |4 aut | |
| 700 | 1 | |a Huerga, Helena |e verfasserin |4 aut | |
| 700 | 1 | |a Franke, Molly F |e verfasserin |4 aut | |
| 700 | 0 | |a endTB Observational Study Team |e verfasserin |4 aut | |
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