A clinical prediction model for unsuccessful pulmonary tuberculosis treatment outcomes.

BACKGROUND Despite widespread availability of curative therapy, tuberculosis treatment outcomes remain suboptimal. Clinical prediction models can inform treatment strategies to improve outcomes. Using baseline clinical data, we developed a prediction model for unsuccessful TB treatment outcome and evaluated the incremental value of HIV-related severity and isoniazid acetylator status. METHODS Data originated from the Regional Prospective Observational Research for Tuberculosis Brazil cohort, which enrolled newly-diagnosed tuberculosis patients in Brazil from 2015-2019. This analysis included participants with culture-confirmed, drug-susceptible pulmonary tuberculosis who started first-line anti-tuberculosis therapy and had ≥12 months of follow-up. The endpoint was unsuccessful tuberculosis treatment: composite of death, treatment failure, regimen switch, incomplete treatment, or not evaluated. Missing predictors were imputed. Predictors were chosen via bootstrapped backward selection. Discrimination and calibration were evaluated with c-statistics and calibration plots, respectively. Bootstrap internal validation estimated overfitting, and a shrinkage factor was applied to improve out-of-sample prediction. Incremental value was evaluated with likelihood ratio-based measures. RESULTS Of 944 participants, 191 (20%) had unsuccessful treatment outcomes. The final model included seven baseline predictors: hemoglobin, HIV-infection, drug use, diabetes, age, education, and tobacco use. The model demonstrated good discrimination (c-statistic=0.77; 95% confidence interval: 0.73-0.80) and was well-calibrated (optimism-corrected intercept and slope: -0.12 and 0.89, respectively). HIV-related factors and isoniazid acetylation status did not improve prediction of the final model. CONCLUSIONS The prediction model, using information readily available at treatment initiation, performed well in this population. The findings may guide future work to allocate resources or inform targeted interventions for high-risk patients.