Cost-effectiveness of latent tuberculosis screening before steroid therapy for idiopathic nephrotic syndrome in children

Abstract

Background: Guidelines differ on screening recommendations for latent tuberculosis infection (LTBI) prior to immunosuppressive therapy. We aimed to determine the most cost-effective LTBI screening strategy before long-term steroid therapy in a child with new-onset idiopathic nephrotic syndrome.

Study design: Markov state-transition model.

Setting & population: 5-year-old boy with new-onset idiopathic nephrotic syndrome.

Model, perspective, & timeframe: The Markov model took a societal perspective over a lifetime horizon.

Intervention: 3 strategies were compared: universal tuberculin skin testing (TST), targeted screening using a risk-factor questionnaire, and no screening. A secondary model included the newer interferon γ release assays (IGRAs), requiring only one visit and having greater specificity than TST.

Outcomes: Marginal cost-effectiveness ratios (2010 US dollars) with effectiveness measured as quality-adjusted life-years (QALYs).

Results: At an LTBI prevalence of 1.1% (the average US childhood prevalence in our base case), a no-screening strategy dominated ($2,201; 29.3356 QALYs) targeted screening ($2,218; 29.3356 QALYs) and universal TST ($2,481; 29.3347 QALYs). At a prevalence >10.3%, targeted screening with a risk-factor questionnaire was the most cost-effective option. Higher than a prevalence of 58.5%, universal TST was preferred. In the secondary model, targeted screening with a questionnaire followed by IGRA testing was cost-effective compared with no screening in the base case when the LTBI prevalence was >4.9%.

Limitations: There is no established gold standard for the diagnosis of LTBI. Results of any modeling task are limited by the accuracy of available data.

Conclusions: Prior to starting steroid therapy, only patients in areas with a high prevalence of LTBI will benefit from universal TST. As more evidence becomes available about the use of IGRA testing in children, the assay may become a component of cost-effective screening protocols in populations with a higher burden of LTBI.

Figure 1. Model structure

Patients enter the first six months of the model with idiopathic nephrotic syndrome. Those surviving the first six months of the model enter the four-state Markov state-transition model either well or with LTBI and remain in it until death. TST, tuberculin skin test; IGRA, interferon-γ release-assay; +, positive; TB, tuberculosis; LTBI, latent tuberculosis infection; INH, isoniazid; −, negative.

Figure 2. Two-way sensitivity analysis examining the risk of LTBI reactivation from immunosuppression and the LTBI prevalence in the primary model

Solid lines represent the willingness to pay thresholds of $100,000/QALY demarcating the tested strategies. As the LTBI prevalence and relative risk of reactivation from immunosuppression increase from the base-case (relative hazard of 7.7 with a LTBI prevalence of 1.1%), targeted screening becomes preferred over no-screen. At a higher LTBI prevalence and relative risk of LTBI reactivation from immunosuppression, universal TST is preferred over targeted screening. TST, tuberculin skin test; LTBI, latent tuberculosis infection; QALY, quality-adjusted life years.

Figure 3. Tornado plot (one-way sensitivity analyses, secondary model) examining targeted IGRA versus no-screen

Parameters are varied across 95% confidence intervals or range of plausible inputs (i.e. the cost of IGRA testing was varied by ±50% of the base-case value of $84.56) with the model most sensitive to inputs (upper and lower values; base-case in italics) at the top of the figure with the widest bars. Arrows show mCERs >$1,000,000/QALY or where the no-screen strategy dominates.