Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.
Br J Clin Pharmacol. 2023 Jul;89(7):1965-1977. doi: 10.1111/bcp.15515. Epub 2022 Sep 29.
Adherence has been shown to be a major predictor of tuberculosis treatment failure and relapse. The current adherence metrics can be improved to provide higher resolution of adherence patterns and identify patients in need of alternative treatment interventions. We investigated how adherence patterns affect treatment outcomes, when adherence is likely to decrease during treatment and which patients are at risk of being nonadherent.
Individual-level data were pooled from 3 clinical trials (n = 3724) for treatment of drug susceptible tuberculosis where monthly or weekly adherence patterns were collected and adherence patterns were quantified to assess the impact of clustered missed doses vs. randomly missed doses on tuberculosis treatment outcomes. Significance was determined through univariate and multivariate cox regression models.
Patients who miss doses in clusters have an increased hazard risk for unfavourable outcomes and missing as little as 4 treatment days in 1 month resulted in 61% higher risk of unfavourable outcomes compared to patients who missed no treatment days (P < .01). Patients older than 50 years, and patients who experienced an adverse event were associated with lower adherence.
Our results show that the pattern in which patients miss their drugs is important to their overall outcomes and missing treatment days in clusters rather than randomly increases the risk of poor outcomes. In the future more intensive and longitudinal adherence measurements will be valuable for clinical trials and regimen design and interpretation.
已有研究表明，治疗依从性是结核病治疗失败和复发的主要预测因素。目前的依从性衡量标准可以进一步改进，以提供更高分辨率的依从性模式，并识别需要替代治疗干预的患者。我们研究了依从性模式如何影响治疗结果，治疗期间依从性可能降低的原因，以及哪些患者有不依从的风险。
我们汇集了 3 项临床试验（n=3724）的个体水平数据，这些试验用于治疗对药物敏感的结核病，其中每月或每周收集一次依从性模式，并对其进行量化，以评估聚集性漏服与随机漏服对结核病治疗结果的影响。通过单变量和多变量 Cox 回归模型确定了统计学意义。
经常漏服药物的患者出现不良结局的风险更高，与未漏服任何治疗日的患者相比，1 个月内漏服 4 天及以上治疗日的患者发生不良结局的风险增加 61%（P<.01）。年龄大于 50 岁的患者和发生不良事件的患者依从性较低。
我们的研究结果表明，患者漏服药物的模式对其整体结局很重要，与随机漏服相比，药物漏服的聚集性增加了不良结局的风险。未来，更密集和纵向的依从性测量将对临床试验和方案设计与解读具有重要价值。
