Figure 5.

Pyrazinamide steady-state area under the concentration–time curve (AUC_ss) associated with primary efficacy and safety outcomes. (A) In the 6-month standard regimen, the therapeutic window of pyrazinamide AUC_ss between 231 and 355 mg·h/L was associated with ≤18% observed grade 3 or higher adverse event while maintaining 95% durable cure at 12 months after treatment initiation. (B) In the 4-month rifapentine–moxifloxacin regimen, therapeutic window of pyrazinamide AUC_ss between 226 and 349 was associated with ≤18% observed grade 3 or higher adverse event. The solid teal line indicates the median probability without tuberculosis (TB)–related unfavorable outcomes at given pyrazinamide AUC_ss, and teal-shaded areas indicate the 95% CI. The solid red lines indicate the median probability of grade 3 or higher adverse event at given pyrazinamide AUC_ss, and red-shaded areas indicate the 95% CI. A solid teal line with shaded areas is not pictured in B, because pyrazinamide AUC_ss was not associated with TB-related unfavorable outcomes for the 4-month rifapentine–moxifloxacin regimen. The teal dotted line shows the pyrazinamide AUC_ss predicted to achieve the targeted primary efficacy outcome threshold. The red dotted line at the upper boundary of the therapeutic window shows the pyrazinamide AUC_ss predicted to achieve the observed primary safety outcome. The red dotted line at the lower boundary of the therapeutic window in B shows the fifth percentile of the pyrazinamide AUC_ss used to predict the primary safety outcome. The purple shade shows the therapeutic window constructed on the basis of the exposure and response relationship described above.