Month 2 Culture Status and Treatment Duration as Predictors of Tuberculosis Relapse Risk in a Meta-Regression Model

Background: New drugs and regimens with the potential to transform tuberculosis treatment are presently in early stage clinical trials. Objective: The goal of the present study was to infer the required duration of these treatments. Method: A meta-regression model was developed to predict relapse risk using treatment duration and month 2 sputum culture positive rate as predictors, based on published historical data from 24 studies describing 58 regimens in 7793 patients. Regimens in which rifampin was administered for the first 2 months but not subsequently were excluded. The model treated study as a random effect. Results: The model predicted that new regimens of 4 or 5 months duration with rates of culture positivity after 2 months of 1% or 3%, would yield relapse rates of 4.0% or 4.1%, respectively. In both cases, the upper limit of the 2-sided 80% prediction interval for relapse for a hypothetical trial with 680 subjects per arm was <10%. Analysis using this model of published month 2 data for moxifloxacin-containing regimens indicated they would result in relapse rates similar to standard therapy only if administered for >= 5 months. Conclusions: This model is proposed to inform the required duration of treatment of new TB regimens, potentially hastening their accelerated approval by several years.