A 24-Week, All-Oral Regimen for Rifampin-Resistant Tuberculosis

Nyang’wa, Bern-Thomas; Berry, Catherine; Kazounis, Emil; Motta, Ilaria; Parpieva, Nargiza; Tigay, Zinaida; Solodovnikova, Varvara; Liverko, Irina; Moodliar, Ronelle; Dodd, Matthew; Ngubane, Nosipho; Rassool, Mohammed; McHugh, Timothy D.; Spigelman, Melvin; Moore, David; Ritmeijer, Koert; Cros, Philipp du; Fielding, Katherine

doi:10.1056/nejmoa2117166

Cited by 182 publications

(158 citation statements)

References 16 publications

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“…Discontinuation of treatment, mainly due to adverse events or adherence issues, was higher in the control group (36.4%) versus any of the 6-month regimens (8–9.9%) and largely explained the superiority of the latter. Though no baseline resistance to any of the regimen components was detected, two participants failed with acquired resistance to at least one drug in the BDQ-PTM-LZD arm [25 ▪▪ ].…”

Section: Ultra-short Multidrug Resistant Tuberculosis Treatment Regim...mentioning

confidence: 91%

Update on drug treatments for multidrug resistant tuberculosis

Davies

Aston

2023

Current Opinion in Infectious Diseases

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Purpose of reviewTo describe important recent developments in the treatment of multidrug resistant tuberculosis (MDR-TB) Recent findingsIn the last decade, novel and repurposed antituberculosis drugs have transformed MDR-TB treatment with improved rates of treatment success, better tolerability and safety and reduced duration. As recently as 2016, standard care relied on up to seven drugs for 24 months with treatment success no better than 70%. Seven drug shorter so-called ''Bangladesh'' style regimens subsequently achieved similar or better results at a duration of 9--12 months but concerns about first-line resistance additional to rifampicin hampered global uptake. After conditional approval in 2012, the novel agent bedaquiline was demonstrated to improve outcomes and reduce mortality when used in longer and shorter regimens, resulting in the replacement of injectable agents. In the last 2 years, clinical trials of all-oral 6-month three or four drug regimens containing bedaquiline, pretomanid and linezolid have shown superior efficacy against both longer and shorter traditional regimens, resulting in major changes in WHO guidance.

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Section: Ultra-short Multidrug Resistant Tuberculosis Treatment Regim...mentioning

confidence: 91%

Update on drug treatments for multidrug resistant tuberculosis

Davies

Aston

2023

Current Opinion in Infectious Diseases

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“…More importantly, rates of adverse effects were high, with 48% of participants experiencing myelosuppression and 81% experiencing peripheral neuropathy, which was largely driven by the use of 1200 mg of linezolid daily [ 4 ]. The ZeNiX and TB-PRACTECAL trials evaluated different dosages of linezolid in MDR-TB patients treated with shorter 3- to 4-drug regimens [ 3 , 6 ].…”

Section: Emergence Of Drug-resistant Tuberculosis and The Evolution O...mentioning

confidence: 99%

“…As expected, shorter linezolid durations and lower doses resulted in less toxicity. In TB-PRACTECAL, participants receiving standard, locally accepted treatment regimens aligned with the WHO guidelines were compared with participants who received bedaquiline, pretomanid, and moxifloxacin in addition to linezolid 600 mg daily for the first 4 months and 300 mg daily for the last 2 months (BPaLM) [ 6 ]. Unfavorable outcomes (composite of failure, death, recurrence, or loss of follow up) were less likely in the BPaLM (11.3%) than in BPaL ([bedaquiline, pretomanid, and linezolid] 23%) or control groups (48.5%).…”

Section: Emergence Of Drug-resistant Tuberculosis and The Evolution O...mentioning

confidence: 99%

At Long Last: Short, All-Oral Regimens for Multidrug-Resistant Tuberculosis in the United States

Sinha

Jacobson

Horsburgh

et al. 2023

Open Forum Infectious Diseases

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Multidrug resistant tuberculosis (MDR-TB) has historically required longer treatment regimens that were associated with higher unfavorable outcomes and side effects rates compared to drug susceptible tuberculosis (DS-TB). During the last decade, several studies conducted mostly in high incidence settings, have shown that MDR-TB can be successfully treated using all-oral shorter regimens of 6-9 months duration. In this paper, we review the evolution of MDR-TB treatment from the early long regimens with injectables agents (IA), followed by the shorter regimens with IA to the groundbreaking all-oral 6-9 months regimens. Finally, we propose a framework for implementation of the shorter all-oral regimens in the United States.

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“…Presented results, which are not published yet, showed that the lower doses and/or shorter duration treatment arms of linezolid had similar success rates and less toxicity in comparison with the treatment arm including 1,200 mg of linezolid for 6 months [ 87 ]. As described in the PA section, the BPaLM regimen was found to be efficacious in the TB-PRACTECAL trial [ 62 , 88 ] and is included in the newest WHO rapid communication [ 19 ]. Another study including linezolid is the MDR-END study, which compares the effectiveness and safety of oral linezolid, delamanid, levofloxacin, and pyrazinamide for 9–12 months with the WHO 2016 MDR-TB regimen for 20–24 months [ 89 ].…”

Section: Repurposed Drugsmentioning

confidence: 99%

“…However, a follow-up meta-analysis in 2018 reported greater treatment success with the use of clofazimine than without it, with an adjusted risk difference of 0.06 (95% CI: 0.01–0.10) [ 117 ]. Very recent results from the TB-PRACTECAL study showed that the bedaquiline, pretomanid, linezolid, and clofazimine regimen was effective and safe, but it was not the most effective and safe regimen within the trial, but this has not been published yet [ 88 , 118 ]. Based on its performance in clinical trials and meta-analyses, clofazimine was categorized as a group B drug in the 2019 WHO consolidated guidelines on MDR-TB treatment [ 20 ].…”

Section: Revived Drugsmentioning

confidence: 99%

New and Repurposed Drugs for the Treatment of Active Tuberculosis: An Update for Clinicians

et al. 2022

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Although tuberculosis (TB) is preventable and curable, the lengthy treatment (generally 6 months), poor patient adherence, high inter-individual variability in pharmacokinetics (PK), emergence of drug resistance, presence of comorbidities, and adverse drug reactions complicate TB therapy and drive the need for new drugs and/or regimens. Hence, new compounds are being developed, available drugs are repurposed, and the dosing of existing drugs is optimized, resulting in the largest drug development portfolio in TB history. This review highlights a selection of clinically available drug candidates that could be part of future TB regimens, including bedaquiline, delamanid, pretomanid, linezolid, clofazimine, optimized (high dose) rifampicin, rifapentine, and para-aminosalicylic acid. The review covers drug development history, preclinical data, PK, and current clinical development.

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A 24-Week, All-Oral Regimen for Rifampin-Resistant Tuberculosis

Cited by 182 publications

References 16 publications

Update on drug treatments for multidrug resistant tuberculosis

Update on drug treatments for multidrug resistant tuberculosis

At Long Last: Short, All-Oral Regimens for Multidrug-Resistant Tuberculosis in the United States

New and Repurposed Drugs for the Treatment of Active Tuberculosis: An Update for Clinicians

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