Cost-effectiveness of Testing and Treatment for Latent Tuberculosis Infection in Residents Born Outside the United States With and Without Medical Comorbidities in a Simulation Model

Abstract

Importance: Testing for and treating latent tuberculosis infection (LTBI) is among the main strategies to achieve TB elimination in the United States. The best approach to testing among non-US born residents, particularly those with comorbid conditions, is uncertain.

Objective: To estimate health outcomes, costs, and cost-effectiveness of LTBI testing and treatment among non-US born residents with and without medical comorbidities.

Design, setting, and participants: Decision analytic tree and Markov cohort simulation model among non-US born residents with no comorbidities, with diabetes, with HIV infection, or with end-stage renal disease (ESRD) using a health care sector perspective with 3% annual discounting. Strategies compared included no testing, tuberculin skin test (TST), interferon gamma release assay (IGRA), confirm positive (initial TST, IGRA only for TST-positive results; both tests positive indicates LTBI), and confirm negative (initial IGRA, then TST for IGRA-negative; any test positive indicates LTBI). All strategies were coupled to treatment with 3 months of self-administered rifapentine and isoniazid.

Main outcomes and measures: Number needed to test and treat to prevent 1 case of TB reactivation, discounted quality-adjusted life-years (QALYs), discounted lifetime medical costs, and incremental cost-effectiveness ratios (ICERs).

Results: Improving health outcomes increased costs, with choice of test dependent on willingness to pay. Strategies ranked by ascending costs and benefits: no testing, confirm positive, TST, IGRA, and confirm negative. The ICERs varied by non-US born patient risk group: patients with no comorbidities, IGRA was likely cost-effective at $83 000/QALY; patients with diabetes, both confirm positive ($53 000/QALY) and IGRA ($120 000/QALY) were likely cost-effective; patients with HIV, confirm negative was clearly preferred ($63 000/QALY); and patients with ESRD, no testing was cost-effective. Increased LTBI prevalence and reduced return for TST reading improved IGRA's relative performance. In 10 000 probabilistic simulations among non-US born patients with no comorbidities, with diabetes, and with HIV, some form of testing was virtually always cost-effective. These simulations highlight the uncertainty of test choice for non-US born patients with no comorbidities and non-US born patients with diabetes, but strategies including IGRA were preferred in over 60% of simulations for all non-US born populations except those with ESRD.

Conclusions and relevance: Testing for and treating LTBI among non-US born residents with and without selected comorbidities is likely cost-effective except among those with ESRD in whom competing risks of death limit benefits. Strategies including IGRA fell below a $100 000/QALY willingness-to-pay threshold for non-US born patients with no comorbidities, patients with diabetes, and patients with HIV.

Figure 1.. Primary Cost-effectiveness Results in Non–US Born Patients

A, The best-performing strategy with an incremental cost-effectiveness ratio (ICER) below $100 000/quality-adjusted life-year (QALY). B, Strategies that are likely to improve health outcomes compared with the strategy indicated in panel A but are associated with ICERs above $100 000/QALY. ICERs are calculated against the next-best alternative strategy and are shown in 2015 US dollars per QALY gained. IGRA indicates interferon gamma release assay.

Figure 2.. Effect of Tuberculin Skin Test (TST) Return and Latent Tuberculosis Infection (LTBI) Prevalence on Cost-effectiveness Conclusions in Non–US Born Patients

A, A 1-way sensitivity analysis demonstrating the effect of TST return on the cost-effectiveness conclusions for interferon gamma release assay (IGRA) testing and IGRA plus TST for sensitivity testing. B, An illustration of the effect of LTBI prevalence on cost-effectiveness conclusions for IGRA testing and confirm negative testing. In the confirm negative strategy, patients first underwent IGRA. If that test was positive, LTBI was diagnosed. If that test was negative, then the patient underwent TST. LTBI was ruled out only if both tests were negative. For each risk population, there is a unique LTBI prevalence above which IGRA requires more investment to gain the same amount of quality-adjusted life-years (QALYs) than confirm negative. Above this point, IGRA is excluded from consideration as a viable strategy and thus is not represented in the figure. The apparent discontinuity at high prevalence (>90% non–US born patients with diabetes, >80% non–US born individuals with no comorbidities) emerges when confirm negative is not only a cost-effective strategy but becomes more favorable than other, less costly strategies. Incremental cost-effectiveness ratios (ICERs) are calculated against the next-best alternative strategy and are shown in 2015 US dollars per QALY gained. End-stage renal disease was excluded from this figure because it is cost-ineffective.

Figure 3.. Cost-effectiveness Acceptability Curves Representing the Proportion of Simulations for Which Each Strategy Was Preferred at a Given Willingness-to-Pay Threshold

Probabilistic sensitivity analysis was performed on reactivation rate, LTBI prevalence, and test characteristics in non–US born persons with no comorbidities (A), those with HIV (B), individuals with diabetes (C), and those with end-stage renal disease (D). IGRA indicates interferon gamma release assay; TST, tuberculin skin test.