Johnson & Johnson Services, Inc., New Brunswick, NJ, USA.
Xian Janssen Pharmaceutical Ltd., Beijing, China.
BMC Infect Dis. 2020 Feb 10;20(1):113. doi: 10.1186/s12879-020-4795-4.
Currently available injectable agents are inadequate to address the high drug-resistant tuberculosis (DR-TB) burden in China. Regimens including the oral agent bedaquiline have been shown to be efficacious and safe, leading to its incorporation into multiple national TB treatment programs. This analysis evaluated the impact of increased adoption of bedaquiline-containing regimens on the DR-TB burden in China.
A state-transition model was developed that permits movement and interaction between susceptible, latent, and active TB disease states, while distinguishing between drug-sensitive (DS) and DR-TB. Model inputs were obtained from the published literature or derived such that model metrics approximated those published by the WHO. Expected improvements in infrastructure were built into the model to forecast the epidemiology of DR-TB in China through 2040 in the absence of bedaquiline (baseline forecast). The impact of higher utilization of bedaquiline-containing regimens (85% peak share) was then assessed in two scenarios that differed with regard to treatment success rates of the regimens: 61% (reflecting findings of clinical trials) and 80% (reflecting data from observational studies), versus the 44% success rate associated with standard-of-care treatment.
In the baseline scenario, the model predicted increases in annual incidence of DR-TB by 6-8% during each five-year period between 2020 and 2040, with an increase of 30% over the entire study duration. Adoption of bedaquiline-based regimens limits the incidence increases to only 1-3% in each five-year period and to 8% over the study duration in the 61% success rate scenario. Incidence declines by 1-6% during each five-year period and by 12% over the study duration in the 80% success rate scenario. Similar effects on DR-TB prevalence (4-5% increase in baseline, 0-7% decline in scenario 1, and 4-19% decline in scenario 2) and mortality (5-7% increase in baseline, 0-16% decline in scenario 1, and 6-40% decline in scenario 2) were seen following bedaquiline adoption.
Incorporation of bedaquiline into DR-TB treatment regimens will significantly reduce the DR-TB burden in China, helping to counter the expected increase in burden in the absence of bedaquiline. The study will provide valuable information to public health policy planners.
目前可用的注射剂不足以解决中国高耐药结核病(DR-TB)的负担。包含口服药物贝达喹啉的方案已被证明是有效和安全的,因此已被纳入多个国家结核病治疗方案。本分析评估了增加使用包含贝达喹啉的方案对中国 DR-TB 负担的影响。
开发了一个状态转移模型,该模型允许在易感、潜伏和活动性结核病疾病状态之间移动和相互作用,同时区分药物敏感(DS)和 DR-TB。模型输入来自已发表的文献或推导得出,以使模型指标近似于世界卫生组织(WHO)公布的指标。将预期的基础设施改善纳入模型中,以预测 2040 年前中国 DR-TB 的流行病学情况(基线预测)。然后,在两种方案中评估了更高比例使用包含贝达喹啉的方案的影响:方案的治疗成功率分别为 61%(反映临床试验结果)和 80%(反映观察性研究数据),而标准护理治疗的成功率为 44%。
在基线方案中,模型预测 2020 年至 2040 年期间,每年 DR-TB 的发病率将增加 6-8%,整个研究期间增加 30%。采用贝达喹啉为基础的方案将发病率增加限制在每个五年期间的 1-3%,在治疗成功率为 61%的方案中,在整个研究期间增加 8%。在治疗成功率为 80%的方案中,每个五年期间发病率下降 1-6%,整个研究期间下降 12%。在基线方案中,DR-TB 患病率(增加 4-5%)和死亡率(增加 5-7%)也有类似的变化。在贝达喹啉采用后,在方案 1 中分别下降 0-16%,在方案 2 中分别下降 6-40%。
将贝达喹啉纳入 DR-TB 治疗方案将显著降低中国 DR-TB 的负担,有助于应对在没有贝达喹啉的情况下预期的负担增加。该研究将为公共卫生政策规划者提供有价值的信息。