Castro Maria Del Mar, Cossio Alexandra, Navas Adriana, Fernandez Olga, Valderrama Liliana, Cuervo-Pardo Lyda, Marquez-Oñate Ricardo, Gómez María Adelaida, Saravia Nancy Gore
Centro Internacional de Entrenamiento e Investigaciones Médicas (CIDEIM), Cali 760031, Colombia.
Universidad Icesi, Cali 760031, Colombia.
Pathogens. 2022 Mar 21;11(3):378. doi: 10.3390/pathogens11030378.
Addition of the immunomodulator pentoxifylline (PTX) to antimonial treatment of mucosal leishmaniasis has shown increased efficacy. This randomized, double-blind, placebo-controlled trial evaluated whether addition of pentoxifylline to meglumine antimoniate (MA) treatment improves therapeutic response in cutaneous leishmaniasis (CL) patients. Seventy-three patients aged 18−65 years, having multiple lesions or a single lesion ≥ 3 cm were randomized to receive: intramuscular MA (20 mg/kg/day × 20 days) plus oral PTX 400 mg thrice daily (intervention arm, n = 36) or MA plus placebo (control arm, n = 37), between 2012 and 2015. Inflammatory gene expression was evaluated by RT-qPCR in peripheral blood mononuclear cells from trial patients, before and after treatment. Intention-to-treat failure rate was 35% for intervention vs. 25% for control (OR: 0.61, 95% CI: 0.21−1.71). Per-protocol failure rate was 32% for PTX, and 24% for placebo (OR: 0.50, 95% CI: 0.13−1.97). No differences in frequency or severity of adverse events were found (PTX = 142 vs. placebo = 140). Expression of inflammatory mediators was unaltered by addition of PTX to MA. However, therapeutic failure was associated with significant overexpression of il1β and ptgs2 (p < 0.05), irrespective of study group. No clinical benefit of addition of PTX to standard treatment was detected in early mild to moderate CL caused by Leishmania (V.) panamensis.
在黏膜利什曼病的锑剂治疗中添加免疫调节剂己酮可可碱（PTX）已显示出疗效提高。这项随机、双盲、安慰剂对照试验评估了在葡甲胺锑（MA）治疗中添加己酮可可碱是否能改善皮肤利什曼病（CL）患者的治疗反应。2012年至2015年期间，73名年龄在18 - 65岁、有多个病灶或单个病灶≥3 cm的患者被随机分为：肌肉注射MA（20 mg/kg/天×20天）加口服PTX 400 mg，每日三次（干预组，n = 36）或MA加安慰剂（对照组，n = 37）。在治疗前后，通过RT-qPCR评估试验患者外周血单核细胞中的炎症基因表达。意向性分析的失败率，干预组为35%，对照组为25%（比值比：0.61，95%置信区间：0.21 - 1.71）。符合方案分析的失败率，PTX组为32%，安慰剂组为24%（比值比：0.50，95%置信区间：0.13 - 1.97）。未发现不良事件的频率或严重程度有差异（PTX组 = 142例，安慰剂组 = 140例）。在MA中添加PTX并未改变炎症介质的表达。然而，无论研究组如何，治疗失败都与il1β和ptgs2的显著过表达相关（p < 0.05）。在由巴拿马利什曼原虫（V.）引起的早期轻度至中度CL中，未检测到在标准治疗中添加PTX有临床益处。
