Specialty Care, Pfizer, Groton, Connecticut, United States of America.
PLoS One. 2013 Aug 5;8(8):e71116. doi: 10.1371/journal.pone.0071116. Print 2013.
New drugs and regimens with the potential to transform tuberculosis treatment are presently in early stage clinical trials.
The goal of the present study was to infer the required duration of these treatments.
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.
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.
This model is proposed to inform the required duration of treatment of new TB regimens, potentially hastening their accelerated approval by several years.
目前，具有改变结核病治疗潜力的新药和新方案正在早期临床试验阶段。
本研究旨在推断这些治疗方法所需的持续时间。
根据 24 项研究中描述的 7793 名患者的 58 种方案的历史数据，开发了一个元回归模型，使用治疗持续时间和第 2 个月痰培养阳性率作为预测因子来预测复发风险。排除了在前 2 个月使用利福平治疗但随后未使用的方案。该模型将研究视为随机效应。
该模型预测，持续时间为 4 或 5 个月，第 2 个月培养阳性率为 1%或 3%的新方案，其复发率分别为 4.0%或 4.1%。在这两种情况下，双侧 80%预测区间上限的假设试验中，每臂 680 例患者的复发率均<10%。使用该模型对含莫西沙星方案的发表的第 2 个月数据进行分析表明，只有在持续治疗 5 个月或更长时间，它们的复发率才与标准治疗相似。
该模型旨在为新的结核病治疗方案的治疗持续时间提供信息，可能会使它们的加速批准提前几年。
