Abstract
SummaryBackgroundIn May, 2016, WHO endorsed a 9 month regimen for multidrug-resistant tuberculosis that is cheaper and potentially more effective than the conventional, longer (20–24 month) therapy. We aimed to investigate the population-level implications of scaling up this new regimen.MethodsIn this population modelling analysis, we developed a dynamic transmission model to simulate the introduction of this short-course regimen as an instantaneous switch in 2016. We projected the corresponding percentage reduction in the incidence of multidrug-resistant tuberculosis by 2024 compared with continued use of longer therapy. In the primary analysis in a representative southeast Asian setting, we assumed that the short-course regimen would double treatment access (through savings in resources or capacity) and achieve long-term efficacy at levels seen in preliminary cohort studies. We then did extensive sensitivity analyses to explore a range of alternative scenarios.FindingsUnder the optimistic assumptions in the primary analysis, the incidence of multidrug-resistant tuberculosis in 2024 would be 3·3 (95% uncertainty range 2·2–5·6) per 100 000 population with the short-course regimen and 4·3 (2·9–7·6) per 100 000 population with continued use of longer therapy—ie, the short-course regimen could reduce incidence by 23% (10–38). Incidence would be reduced by 14% (4–28) if the new regimen affected only treatment effectiveness and by 11% (3–24) if it affected only treatment availability. Under more pessimistic assumptions, the short-course regimen would have minimal effect and even potential for harm—eg, when 30% of patients are ineligible for the new regimen because of second-line drug resistance, we projected a change in incidence of −2% (−20 to +28). The new regimen's effect was greater in settings with more ongoing transmission of multidrug-resistant tuberculosis, but results were otherwise similar across settings with different levels of tuberculosis incidence and prevalence of multidrug resistance.InterpretationThe short-course regimen has potential to substantially lessen the multidrug-resistant tuberculosis epidemic, but this effect depends on its long-term efficacy, its ability to expand treatment access, and the role of second-line drug resistance.FundingUS National Institutes of Health and Bill & Melinda Gates Foundation.
Highlights
Multidrug-resistant tuberculosis—present in 3–4% of new tuberculosis cases and 20% of previously treated cases worldwide—causes 190 000 deaths each year and is a major challenge to clinicians and policy makers.[1]
We explored the extent to which the anticipated effect depends on characteristics of the regimen that remain to be determined, such as treatment success under programmatic conditions, durability of effectiveness, exclusions on the basis of additional drug resistance, treatment outcomes after such exclusions, and the extent to which cost savings from the new regimen can be used to expand treatment access
Modelling of short-course regimen We modelled the introduction of a short-course regimen as an instantaneous switch from the conventional, longer therapy in 2016 for patients who are diagnosed with multidrug-resistant tuberculosis and not found to have additional drug resistance that makes them ineligible
Summary
Multidrug-resistant tuberculosis—present in 3–4% of new tuberculosis cases and 20% of previously treated cases worldwide (with much higher prevalence in some countries)—causes 190 000 deaths each year and is a major challenge to clinicians and policy makers.[1]. In May, 2016, WHO made a conditional recommendation for a new short-course regimen that can treat most patients with multidrugresistant tuberculosis in 9–12 months.[8] This regimen consists of an initial 4–6 month phase of seven drugs including a second-line injectable, followed by a 5 month continuation of four of the oral drugs including pyrazinamide and a fluoroquinolone. It costs less than US$1000 per patient and has shown promising effectiveness, with more than 80% of patients cured in www.thelancet.com/respiratory Vol 5 March 2017
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