Abstract
BackgroundRegimens that could treat both rifampin-resistant (RR) and rifampin-susceptible tuberculosis (TB) while shortening the treatment duration have reached late-stage clinical trials. Decisions about whether and how to implement such regimens will require an understanding of their likely clinical impact and how this impact depends on local epidemiology and implementation strategy.MethodsA Markov state-transition model of 100,000 representative South African adults with TB was used to simulate implementation of the regimen BPaMZ (bedaquiline, pretomanid, moxifloxacin, and pyrazinamide), either for RR-TB only or universally for all patients. Patient outcomes, including cure rates, time with active TB, and time on treatment, were compared to outcomes under current care. Sensitivity analyses varied the drug-resistance epidemiology, rifampin susceptibility testing practices, and regimen efficacy.ResultsUsing BPaMZ exclusively for RR-TB increased the proportion of all RR-TB that was cured by initial treatment from 60 ± 1% to 67 ± 1%. Expanding use of BPaMZ to all patients increased cure of RR-TB to 89 ± 1% and cure of all TB from 87.3 ± 0.1% to 89.5 ± 0.1%, while shortening treatment by 1.9 months/person. In sensitivity analyses, reducing the coverage of rifampin susceptibility testing resulted in lower projected proportions of patients cured under all regimen scenarios (current care, RR-only BPaMZ, and universal BPaMZ), compared to the proportions projected using South Africa’s high coverage; however, this reduced coverage resulted in greater expected incremental benefits of universal BPaMZ implementation, both when compared to RR-only BPaMZ implementation and when compared to to current care under the same low rifampin susceptibility testing coverage. In settings with higher RR-TB prevalence, the benefits of BPaMZ were magnified both for RR-specific and universal BPaMZ implementation.ConclusionsNovel regimens such as BPaMZ could improve RR-TB outcomes and shorten treatment for all patients, particularly with universal use. Decision-makers weighing early options for implementing such regimens at scale will want to consider the expected impact on patient outcomes and on the burden of treatment in their local context.
Highlights
Regimens that could treat both rifampin-resistant (RR) and rifampin-susceptible tuberculosis (TB) while shortening the treatment duration have reached late-stage clinical trials
Modeling a South African TB cohort, we have estimated that implementing the BPaMZ regimen universally could simultaneously increase the percentage of patients with RR-TB who are cured from 60% to nearly 90%, maintain nearly 90% cure among patients with RS-TB, reduce treatment duration by 2 months or more per patient, and reduce infectious person-time by 3% (RS-TB) to 50% (RR-TB)
Novel drugs are reshaping drug-resistant TB treatment and could soon transform the broader TB treatment landscape if ongoing clinical trial evaluations identify regimens that improve upon current first-line treatment
Summary
Regimens that could treat both rifampin-resistant (RR) and rifampin-susceptible tuberculosis (TB) while shortening the treatment duration have reached late-stage clinical trials. Shorter and more universally effective regimens which treat both rifampin-susceptible (RS) and RR-TB in 6 months or less could be transformative [3] One potential such regimen in late-stage clinical development is BPaMZ, which combines the novel TB drugs bedaquiline (B) and pretomanid (Pa) with the first-line TB drug pyrazinamide (Z) and the third-generation fluoroquinolone moxifloxacin (M). A phase 2c/3 trial of the BPaMZ regimen (SimpliciTB) is underway, evaluating its potential to both shorten treatment to 4 months for patients with drugsusceptible TB and effectively treat (as a 6-month regimen, because of their higher risk of associated resistance to pyrazinamide) patients with rifampin- or multidrug-resistant TB [6]
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