MRC Clinical Trials Unit at University College London, London, UK.
Keya Medical Research Unit, Nairobi, Kenya.
BMC Infect Dis. 2018 Jul 11;18(1):317. doi: 10.1186/s12879-018-3230-6.
The incidence and severity of tuberculosis chemotherapy toxicity is poorly characterised. We used data available from patients in the REMoxTB trial to provide an assessment of the risks associated with the standard regimen and two experimental regimens containing moxifloxacin.
All grade 3 & 4 adverse events (AEs) and their relationship to treatment for patients who had taken at least one dose of therapy in the REMoxTB clinical trial were recorded. Univariable logistic regression was used to test the relationship of baseline characteristics to the incidence of grade 3 & 4 AEs and significant characteristics (p < 0.10) were incorporated into a multivariable model. The timing of AEs during therapy was analysed in standard therapy and the experimental arms. Logistic regression was used to investigate the relationship between AEs (total and related-only) and microbiological cure on treatment.
In the standard therapy arm 57 (8.9%) of 639 patients experienced ≥1 related AEs with 80 of the total 113 related events (70.8%) occurring in the intensive phase of treatment. Both four-month experimental arms ("isoniazid arm" with moxifloxacin substituted for ethambutol & "ethambutol arm" with moxifloxacin substituted for isoniazid) had a lower total of related grade 3 & 4 AEs than standard therapy (63 & 65 vs 113 AEs). Female gender (adjOR 1.97, 95% CI 0.91-1.83) and HIV-positive status (adjOR 3.33, 95% CI 1.55-7.14) were significantly associated with experiencing ≥1 related AE (p < 0.05) on standard therapy. The most common adverse events on standard therapy related to hepatobiliary, musculoskeletal and metabolic disorders. Patients who experienced ≥1 related AE were more likely to fail treatment or relapse (adjOR 3.11, 95% CI 1.59-6.10, p < 0.001).
Most AEs considered related to standard therapy occurred in the intensive phase of treatment with female patients and HIV-positive patients demonstrating a significantly higher risk of AEs during treatment. Almost a tenth of standard therapy patients had a significant side effect, whereas both experimental arms recorded a lower incidence of toxicity. That patients with one or more AE are more likely to fail treatment suggests that treatment outcomes could be improved by identifying such patients through targeted monitoring.
结核病化学治疗毒性的发生率和严重程度描述不足。我们利用 REMoxTB 试验中患者的数据，评估了包含莫西沙星的标准方案和两种实验方案相关的风险。
记录了 REMoxTB 临床试验中至少接受一剂治疗的患者的所有 3 级和 4 级不良事件（AE）及其与治疗的关系。使用单变量逻辑回归测试基线特征与 3 级和 4 级 AE 发生率的关系，将有显著意义的特征（p<0.10）纳入多变量模型。分析标准治疗组和实验治疗组中 AE 的发生时间。使用逻辑回归分析 AE（总 AE 和仅相关 AE）与治疗期间的微生物学治愈率的关系。
在标准治疗组中，639 名患者中有 57 名（8.9%）经历了≥1 次相关 AE，113 次总相关事件中有 80 次（70.8%）发生在治疗强化期。两种 4 个月的实验治疗组（用莫西沙星替代乙胺丁醇的“异烟肼组”和用莫西沙星替代异烟肼的“乙胺丁醇组”）的总相关 3 级和 4 级 AE 数量均低于标准治疗组（63 例和 65 例比 113 例 AE）。女性（调整后的比值比 1.97，95%可信区间 0.91-1.83）和 HIV 阳性（调整后的比值比 3.33，95%可信区间 1.55-7.14）与标准治疗中经历≥1 次相关 AE 显著相关（p<0.05）。标准治疗中最常见的与肝、胆、肌肉骨骼和代谢紊乱相关的不良事件。经历≥1 次相关 AE 的患者更有可能治疗失败或复发（调整后的比值比 3.11，95%可信区间 1.59-6.10，p<0.001）。
大多数被认为与标准治疗相关的 AE 发生在治疗强化期，女性患者和 HIV 阳性患者在治疗期间发生 AE 的风险显著更高。近十分之一的标准治疗患者出现了严重的副作用，而两个实验治疗组的毒性发生率较低。有一个或多个 AE 的患者更有可能治疗失败，这表明通过有针对性的监测来识别这些患者，可以改善治疗结果。
