Bayer Pharmaceuticals, Sant Joan Despi, Spain.
Bayer AG, Berlin, Germany.
PLoS Negl Trop Dis. 2021 Oct 4;15(10):e0009801. doi: 10.1371/journal.pntd.0009801. eCollection 2021 Oct.
Nifurtimox is indicated in Chagas disease but determining its effectiveness in chronic disease is hindered by the length of time needed to demonstrate negative serological conversion. We manually reviewed long-term follow-up data from hospital records of patients with chronic Chagas disease (N = 1,497) in Argentina diagnosed during 1967-1980. All patients were aged ≥18 years at diagnosis and were either treated with nifurtimox (n = 968) or received no antitrypanosomal treatment (n = 529). The primary endpoint was negative seroconversion (the "event"), defined as a change from positive to negative in the serological or parasitological laboratory test used at diagnosis. Time to event was from baseline visit to date of endpoint event or censoring. The effectiveness of nifurtimox versus no treatment was estimated with Cox proportional hazard regression using propensity scores with overlap weights to calculate the hazard ratio and 95% confidence interval. The nifurtimox group was younger than the untreated group (mean, 32.4 vs. 40.3 years), with proportionally fewer females (47.9% vs. 60.1%), and proportionally more of the nifurtimox group than the untreated group had clinical signs and symptoms of Chagas disease at diagnosis (28.9% vs. 14.0%). Median maximum daily dose of nifurtimox was 8.0 mg/kg/day (interquartile range [IQR]: 8.0-9.0) and median treatment duration was 44 days (IQR: 1-90). Median time to event was 2.1 years (IQR: 1.0-4.5) for nifurtimox-treated and 2.4 years (IQR: 1.0-4.2) for untreated patients. Accounting for potential confounders, the estimated hazard ratio (95% confidence interval) for negative seroconversion was 2.22 (1.61-3.07) favoring nifurtimox. Variable treatment regimens and follow-up duration, and an uncommonly high rate of spontaneous negative seroconversion, complicate interpretation of this epidemiological study, but with the longest follow-up and largest cohort analyzed to date it lends weight to the benefit of nifurtimox in adults with chronic Chagas disease. Trial registration: The study protocol was registered at ClinicalTrials.gov: NCT03784391.
硝呋替莫适用于恰加斯病，但由于需要很长时间才能证明血清学转换呈阴性，因此确定其在慢性疾病中的疗效存在阻碍。我们手动查阅了阿根廷一家医院记录的慢性恰加斯病（1967 年至 1980 年间确诊）患者的长期随访数据（N=1497）。所有患者在确诊时均≥18 岁，要么接受了硝呋替莫治疗（n=968），要么未接受抗锥虫治疗（n=529）。主要终点是血清学阴性转换（“事件”），定义为诊断时使用的血清学或寄生虫学实验室检测结果由阳性转为阴性。从基线访视到终点事件或删失时间为事件时间。使用倾向评分重叠权重计算 Cox 比例风险回归来估计硝呋替莫与未治疗组的疗效，计算风险比和 95%置信区间。硝呋替莫组比未治疗组年轻（平均年龄 32.4 岁 vs. 40.3 岁），女性比例较低（47.9% vs. 60.1%），且诊断时，硝呋替莫组比未治疗组更有更多的临床体征和症状（28.9% vs. 14.0%）。硝呋替莫的最大日剂量中位数为 8.0mg/kg/天（四分位距[IQR]：8.0-9.0），治疗持续时间中位数为 44 天（IQR：1-90）。硝呋替莫治疗组的中位事件时间为 2.1 年（IQR：1.0-4.5），未治疗组为 2.4 年（IQR：1.0-4.2）。考虑到潜在混杂因素，阴性血清学转换的估计风险比（95%置信区间）为 2.22（1.61-3.07），有利于硝呋替莫。治疗方案和随访时间存在差异，且自发阴性血清学转换率异常高，这使得这项流行病学研究的解释变得复杂，但考虑到随访时间最长且分析的队列最大，这使得硝呋替莫对慢性恰加斯病成人的益处更具分量。试验注册：该研究方案在 ClinicalTrials.gov 注册：NCT03784391。
