南非耐多药结核病患者接受氯法齐明治疗的剂量相关疗效。
Dose-related treatment outcomes in South African patients prescribed clofazimine for drug-resistant tuberculosis.
机构信息
Discipline of Pharmaceutical Sciences, School of Health Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
出版信息
S Afr Med J. 2020 Dec 14;111(1):61-67. doi: 10.7196/SAMJ.2020.v111i1.14605.
BACKGROUND
Optimal drug levels and minimal toxicity are critical factors in improving treatment outcomes for patients' prescribed new and repurposed medicine for drug-resistant (DR) tuberculosis (TB). The optimal dose of clofazimine (CFZ), a repurposed medicine for DR-TB, that is safe and effective in the South African (SA) population is unknown.
OBJECTIVES
To report on dose-related final treatment outcomes in patients receiving CFZ plus a background regimen for DR-TB.
METHODS
In a retrospective review of patient folders from 2012 to 2014, treatment outcomes documented for patients receiving high- (≥200 mg) and low-dose (100 mg) CFZ in a centralised DR-TB hospital in KwaZulu-Natal Province, SA, were investigated for an association between dose-weight interactions and outcomes.
RESULTS
A total of 600 patients were included, of whom 169 (28.2%) received 100 mg. Of these, 87 (51.5%) weighed <50 kg and 82 (48.5%) ≥50 kg. Four hundred and thirty-one (71.8%) received ≥200 mg, of whom 41 (9.5%) were <50 kg and 390 (90.5%) ≥50 kg. Overall 77.2% were HIV-positive, with 93.95% on antiretroviral medicine. The majority of patients presented with extremely drug-resistant TB (55.3%). Forty-seven and a half percent of patients received a standardised background regimen, and 52.5% received an individualised regimen containing a new or repurposed medicine including CFZ. On multivariate analysis, adjusting for age, gender, HIV status and concomitant antiretrovirals, previous TB history, type of TB and background regimen, patients ≥50 kg prescribed 100 mg CFZ were 60% less likely to have a successful outcome (adjusted odds ratio (OR) 0.4; 95% confidence interval (CI) 0.2 - 0.8; p=0.009) compared with patients <50 kg receiving 100 mg CFZ. Patients <50 kg who received ≥200 mg were 40% less likely to have a successful treatment outcome (adjusted OR 0.6, p=0.3), and were found to have a higher risk of adverse events than patients <50 kg receiving 100 mg CFZ (82.9% v. 65.5%).
CONCLUSIONS
Dose-weight interaction plays a role in the odds of a successful outcome. There is an association between dose-weight interactions, outcomes and adverse events. Weight-based dosing in patients <50 kg and ≥50 kg must be considered to achieve optimal treatment outcomes and reduce adverse events. Active drug safety monitoring must be implemented as a package of care for patients receiving CFZ as part of a DR-TB treatment regimen.
背景
对于新的和重新应用的药物治疗耐药性（DR）结核病（TB）的患者，药物水平最佳和毒性最小是改善治疗结果的关键因素。在南非（SA）人群中，氯法齐明（CFZ）的最佳剂量（一种用于 DR-TB 的重新应用药物）是安全有效的，但目前尚不清楚。
目的
报告接受 CFZ 加背景方案治疗 DR-TB 的患者与剂量相关的最终治疗结果。
方法
在对 2012 年至 2014 年期间患者文件夹的回顾性研究中，调查了在南非夸祖鲁-纳塔尔省的一个中央 DR-TB 医院接受高剂量（≥200mg）和低剂量（100mg）CFZ 的患者的治疗结局与剂量-体重相互作用之间的关系。
结果
共纳入 600 例患者，其中 169 例（28.2%）接受 100mg。其中，87 例（51.5%）体重<50kg，82 例（48.5%）体重≥50kg。431 例（71.8%）接受了≥200mg，其中 41 例（9.5%）体重<50kg，390 例（90.5%）体重≥50kg。总体而言，77.2%的患者 HIV 阳性，93.95%接受抗逆转录病毒药物治疗。大多数患者患有极度耐药性结核病（55.3%）。47.5%的患者接受了标准化的背景方案，52.5%的患者接受了含有新的或重新应用药物（包括 CFZ）的个体化方案。多变量分析显示，调整年龄、性别、HIV 状态和抗逆转录病毒药物、既往结核病史、结核病类型和背景方案后，体重≥50kg 且接受 100mg CFZ 的患者与体重<50kg 且接受 100mg CFZ 的患者相比，成功治疗结局的可能性低 60%（调整后的优势比（OR）0.4；95%置信区间（CI）0.2-0.8；p=0.009）。体重<50kg 且接受≥200mg CFZ 的患者成功治疗结局的可能性低 40%（调整后的 OR 0.6，p=0.3），且与体重<50kg 且接受 100mg CFZ 的患者相比，发生不良事件的风险更高（82.9%对 65.5%）。
结论
剂量-体重相互作用在成功治疗结局的可能性中起着作用。剂量-体重相互作用、结局和不良事件之间存在关联。必须考虑体重为 50kg 以下和 50kg 以上的患者的剂量-体重关系，以实现最佳治疗结局并减少不良事件。必须实施以药物安全性监测为重点的治疗方案，以确保为接受 CFZ 治疗的患者提供最佳的护理，CFZ 是治疗耐药性结核病的方案之一。
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