背景:新的证据表明,缩短,利福平耐药结核病(RR-TB)的简化治疗方案可实现与更长治疗方案相当的治疗结束(EOT)结局.我们比较了含有bedaquiline的6个月方案,Pretomanid,利奈唑胺,根据药物敏感性试验(DST)是否检测到氟喹诺酮耐药(FQ-R),使用9个月或18个月的治疗方案和莫西沙星(BPaLM)作为标准治疗策略.
结果:主要目标是确定6个月的BPaLM是否是RR-TB的具有成本效益的治疗策略。我们使用基因组和人口统计学数据对数学模型进行参数化,以质量调整生命年(QALYs)和2022年美元($)衡量的长期健康结果为每个治疗策略的15岁及以上的患者诊断患有肺部RR-TB在摩尔多瓦,一个结核病耐药负担很高的国家。对于每个人来说,我们模拟了结核病的自然史和相关的治疗结果,以及获得12种抗结核药物耐药性的过程。与护理标准相比,6个月的BPaLM具有成本效益。据估计,这一策略可将每个人的终身成本降低3,366美元(95%UI:[1,465,5,742]p<0.001),QALYs无显著变化(-0.06;95%UI:[-0.49,0.032]p=0.790)。对于那些在BPaLM方案下停止莫西沙星的人,与继续单独使用BPaL相比,继续使用BPaL加氯法齐明(BPaLC)以更低的成本提供了更多的QALY。基于6个月BPaLM的策略至少有93%的机会具有成本效益,只要在停用莫西沙星的情况下继续使用BPaLC。6个月的BPaLM也减少了对阿米卡星耐药的结核病的平均时间,bedaquiline,氯法齐明,环丝氨酸,莫西沙星,还有吡嗪酰胺,同时增加了对delamanid和pretomanid耐药的结核病的平均时间。敏感性分析显示,6个月的BPaLM在BPaLM的相对有效性方面具有成本效益,以及具有FQ-R的队列的比例与护理标准相比,预计6个月的BPaLM将为摩尔多瓦的国家结核病计划节省710万美元(95%UI:[130万,1,540万]p=0.002)在实施后的5年内。我们的分析没有考虑到特定药物之间关于治疗结果的所有可能的相互作用。阻力获取,或特定类型的严重不良事件的后果,我们也没有对干预可能如何影响TB传播动力学进行建模.
结论:与标准护理相比,更长的方案,6个月BPaLM方案的实施可以提高诊断为RR-TB的患者的护理成本效益,特别是在耐药结核病负担较高的环境中。可能需要进一步的研究来探索在不同的耐药结核病负担和国民收入水平的环境中,较短的RR-TB方案的影响和成本效益。
BACKGROUND: Emerging evidence suggests that shortened, simplified treatment regimens for rifampicin-resistant tuberculosis (RR-TB) can achieve comparable end-of-treatment (EOT) outcomes to longer regimens. We compared a 6-month regimen containing bedaquiline, pretomanid, linezolid, and
moxifloxacin (BPaLM) to a standard of care strategy using a 9- or 18-month regimen depending on whether fluoroquinolone resistance (FQ-R) was detected on drug susceptibility testing (DST).
RESULTS: The primary objective was to determine whether 6 months of BPaLM is a cost-effective treatment strategy for RR-TB. We used genomic and demographic data to parameterize a mathematical model estimating long-term health outcomes measured in quality-adjusted life years (QALYs) and lifetime costs in 2022 USD ($) for each treatment strategy for patients 15 years and older diagnosed with pulmonary RR-TB in Moldova, a country with a high burden of TB drug resistance. For each individual, we simulated the natural history of TB and associated treatment outcomes, as well as the process of acquiring resistance to each of 12 anti-TB drugs. Compared to the standard of care, 6 months of BPaLM was cost-effective. This strategy was estimated to reduce lifetime costs by $3,366 (95% UI: [1,465, 5,742] p < 0.001) per individual, with a nonsignificant change in QALYs (-0.06; 95% UI: [-0.49, 0.03] p = 0.790). For those stopping
moxifloxacin under the BPaLM regimen, continuing with BPaL plus clofazimine (BPaLC) provided more QALYs at lower cost than continuing with BPaL alone. Strategies based on 6 months of BPaLM had at least a 93% chance of being cost-effective, so long as BPaLC was continued in the event of stopping
moxifloxacin. BPaLM for 6 months also reduced the average time spent with TB resistant to amikacin, bedaquiline, clofazimine, cycloserine,
moxifloxacin, and pyrazinamide, while it increased the average time spent with TB resistant to delamanid and pretomanid. Sensitivity analyses showed 6 months of BPaLM to be cost-effective across a broad range of values for the relative effectiveness of BPaLM, and the proportion of the cohort with FQ-R. Compared to the standard of care, 6 months of BPaLM would be expected to save Moldova\'s national TB program budget $7.1 million (95% UI: [1.3 million, 15.4 million] p = 0.002) over the 5-year period from implementation. Our analysis did not account for all possible interactions between specific drugs with regard to treatment outcomes, resistance acquisition, or the consequences of specific types of severe adverse events, nor did we model how the intervention may affect TB transmission dynamics.
CONCLUSIONS: Compared to standard of care, longer regimens, the implementation of the 6-month BPaLM regimen could improve the cost-effectiveness of care for individuals diagnosed with RR-TB, particularly in settings with a high burden of drug-resistant TB. Further research may be warranted to explore the impact and cost-effectiveness of shorter RR-TB regimens across settings with varied drug-resistant TB burdens and national income levels.