Effect of introducing ethambutol and integrating drugs into fixed-dose tablets on mortality in tuberculosis patients

Background In response to increasing primary resistance to isoniazid, the Brazilian Ministry of Health modified the tuberculosis (TB) treatment regimen at the end of 2009. The changes included adding ethambutol to the intensive phase, using fixed-dose combination tablets and adjusting isoniazid and pyrazinamide dosages. This study aimed to estimate the effect of the regimen change on all-cause mortality and, secondarily, on TB-specific mortality, treatment success and loss to follow-up. Methods We analysed cohorts of individuals ≥10 y of age who initiated TB treatment before (n = 145 528) and after (n = 161 264) the regimen change. Data were obtained from the national notifiable disease and mortality information systems. Missing data were imputed and effects were estimated using multilevel logistic regression models with states as the clustering level. Covariates were selected using a directed acyclic graph. Results The regimen change was not associated with all-cause mortality (relative risk [RR] 1.01 [95% confidence interval {CI} 0.98 to 1.04]) or TB-specific mortality (RR 0.98 [95% CI 0.95 to 1.02]). The treatment success rate was lower, and loss to follow-up was higher during the modified regimen period compared with the previous one. However, sensitivity analyses suggest that changes in the handling of transfers and missing outcome data may partly explain these findings. Conclusion We concluded that the modified regimen did not adversely affect survival among TB patients.