Cost-Effectiveness of Treating Multidrug-Resistant Tuberculosis

Background: Despite the existence of effective drug treatments, tuberculosis (TB) causes 2 million deaths annually worldwide. Effective treatment is complicated by multidrug-resistant TB (MDR TB) strains that respond only to second-line drugs. We projected the health benefits and cost-effectiveness of using drug susceptibility testing and second-line drugs in a lower-middle-income setting with high levels of MDR TB. Methods and Findings: We developed a dynamic state-transition model of TB. In a base case analysis, the model was calibrated to approximate the TB epidemic in Peru, a setting with a smear-positive TB incidence of 120 per 100,000 and 4.5% MDR TB among prevalent cases. Secondary analyses considered other settings. The following strategies were evaluated: first-line drugs administered under directly observed therapy (DOTS), locally standardized second-line drugs for previously treated cases (STR1), locally standardized second-line drugs for previously treated cases with test-confirmed MDR TB (STR2), comprehensive drug susceptibility testing and individualized treatment for previously treated cases (ITR1), and comprehensive drug susceptibility testing and individualized treatment for all cases (ITR2). Outcomes were costs per TB death averted and costs per quality-adjusted life year (QALY) gained. We found that strategies incorporating the use of second-line drug regimens following first-line treatment failure were highly cost-effective compared to strategies using first-line drugs only. In our base case, standardized second-line treatment for confirmed MDR TB cases (STR2) had an incremental cost-effectiveness ratio of $720 per QALY ($8,700 per averted death) compared to DOTS. Individualized second-line drug treatment for MDR TB following first-line failure (ITR1) provided more benefit at an incremental cost of $990 per QALY ($12,000 per averted death) compared to STR2. A more aggressive version of the individualized treatment strategy (ITR2), in which both new and previously treated cases are tested for MDR TB, had an incremental cost-effectiveness ratio of $11,000 per QALY ($160,000 per averted death) compared to ITR1. The STR2 and ITR1 strategies remained cost-effective under a wide range of alternative assumptions about treatment costs, effectiveness, MDR TB prevalence, and transmission. Conclusions: Treatment of MDR TB using second-line drugs is highly cost-effective in Peru. In other settings, the attractiveness of strategies using second-line drugs will depend on TB incidence, MDR burden, and the available budget, but simulation results suggest that individualized regimens would be cost-effective in a wide range of situations. Background.: Tuberculosis (TB) remains one of the most entrenched diseases on the planet—an estimated one in three people worldwide are infected with Mycobacterium tuberculosis, which causes the disease. Although effective drugs exist, a major reason for the failure to stem the spread of TB lies in the rise of drug-resistant strains of the bacterium. Some strains are resistant to several drugs; patients with this sort of infection are said to have multidrug-resistant (MDR) TB. The development of drug-resistant strains is fostered when health-care workers do not follow treatment guidelines or fail to ensure that patients take the whole treatment course. The World Health Organization recommends an approach to TB control called “DOTS,” which has been adopted by many countries. (See the link below for an explanation of what DOTS involves.) The antibiotics that are used in DOTS are described as “first-line” treatment drugs. They are highly effective against non-resistant TB but much less so against MDR TB. There are other, more expensive, “second-line” antibiotics that perform better against MDR TB. Why Was This Study Done?: Despite the worrying rise in MDR TB cases, the much higher cost of using second-line drugs is prompting some policy-makers to question the merits of introducing them in poor countries with limited resources. However, with MDR TB accounting for nearly a third of TB cases in some countries, first-line therapies seem unlikely to be sufficient in the long term. Second-line strategies, or “DOTS-Plus” strategies, are either standardized for a particular region or are chosen for individual patients on the basis of drug susceptibility tests. The researchers wanted to investigate whether standardized or individualized second-line regimens could save lives and be cost-effective in poor countries. What Did the Researchers Do and Find?: The researchers used a method called modeling. They took information already available about TB in Peru, where for every 100,000 people there are 120 new TB infections every year, and 4.5% of existing cases are MDR TB. The researchers then calculated what might happen over the next 30 years, comparing the likely effects of five alternative strategies. In four, new cases were given first-line drugs for 6 months. Those who were not cured were then treated in different ways. In DOTS, they were retreated with a second course of the same drugs; in STR1 they were given an 18-month standardized course of second-line and first-line drugs; in STR2, only confirmed MDR TB patients were given an 18-month standardized course of second-line and first-line drugs; and in ITR1, confirmed MDR TB patients were given a personalized regimen of second-line drugs. The fifth strategy, ITR2, tested all patients for drug susceptibility at the outset of treatment, and those with MDR TB were given an individualized course; those not cured were tested again and given another individualized course. What Do These Findings Mean?: Despite the slightly higher cost of ITR1, the extra number of lives it would save compared with STR2 makes it a good approach for treatment in Peru. However, cost-effectiveness varies with other factors. If the difference in cost between the two strategies became higher than $9,500 per patient, STR would be preferable. And, if MDR TB were present in 10% of all TB cases, ITR2—with comprehensive drug susceptibility testing for all TB patients—would be best. Additional Information.: Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030241. Resch and colleagues found that treatment of MDR TB using second-line drugs is highly cost-effective in Peru.