聚乙二醇化重组集成干扰素在丙型肝炎受试者中耐受性和早期疗效分析

发布时间：2018-11-18 20:04

【摘要】：研究背景：丙型肝炎是全球范围面临的难题，已经被批准上市的抗丙型肝炎病毒的药物并不是对所有患者都是有效的。一些难治型患者可能会获益于重组集成干扰素(CIFN)，聚乙二醇化重组集成干扰素(PEG-CIFN)可能更有效和更安全。目的：以慢性丙型肝炎患者为受试者，探索和评价聚乙二醇化重组集成干扰素（PEG-CIFN)）的耐受性和早期疗效，为开发一种更安全和更有效的干扰素奠定基础。方法：48名慢性丙型肝炎患者参加此次PEG-CIFNⅠ期临床试验。随机分为5组，分别为PEG-CIFN1.0μg/kg(10人)、PEG-CIFN1.5μg/kg(10人)、PEG-CIFN2.0μg/kg(9人)、PEG-CIFN3.0μg/kg(10人)，四个剂量组进行爬坡试验。PEG-IFNα-2a (派罗欣180μg/次)(9人)为阳性对照组。PEG-CIFN3.0μg/kg组受试者共给药4周，仅进行多次给药耐受性观察。其余4组受试者共需进行14周试验，每周皮下给药1次，第2周和第14周不给药用于采集药代动力学血标本。每周进行症状观察和实验室检查，用于监测不良反应及调整给药剂量。0周、4周、8周、14周进行HCV RNA定量及相关的安全性检测指标测定。结果：所有受试者没有出现中止研究的情况，对药物的耐受性较好。PEG-CIFN各剂量组(PEG-CIFN1.0、1.5、2.0μg/kg)降低血小板的作用比PEG-IFNα-2a (派罗欣)组缓和。PEG-CIFN1.5μg/kg组、PEG-CIFN2.0μg/kg组、PEG-CIFN3.0μg/kg组和PEG-IFNα-2a (派罗欣)180μg组的“快速应答率”(“RVR”）分别为70%(7/10)、77.8%(7/9)、60%(6/10)、77.8%(7/9)。而PEG-CIFN1.0μg/kg组的RVR仅为10%(1/10)。PEG-CIFN1.0μg/kg组、PEG-CIFN1.5μg/kg组、PEG-CIFN2.0μg/kg组和PEG-IFNα-2a180μg组的“延伸快速应答率”(“eRVR”）分别为10%(1/10)、70%(7/10)、77.8%(7/9)、66.7%(6/9)。PEG-CIFN1.0μg/kg组、PEG-CIFN1.5μg/kg组、PEG-CIFN2.0μg/kg组和PEG-IFNα-2a180μg组的“早期应答率”(“EVR”）分别为30%(3/10)、90%(9/10)、88.8%(8/9)、88.8%(8/9)。结论：丙型肝炎患者对PEG-CIFN各剂量组(1.0、1.5、2.0、3.0μg/kg)是可以耐受的。PEG-CIFN1.5、2.0μg/kg组的病毒学应答率与PEG-IFNα-2a组相近，无统计学差异。综合考虑，PEG-CIFN1.5μg/kg可以作为临床推荐剂量。PEG-CIFN的疗效是剂量依赖的。PEG-CIFN可能对1b型HCV感染有较好疗效。在治疗第4周、8周、14周,PEG-CIFN比PEG-IFNα-2a能更好地维持血小板水平。
[Abstract]:Background: hepatitis C is a worldwide challenge, and approved anti-HCV drugs are not effective for all patients. Some refractory patients may benefit from recombinant integrated interferon (CIFN), polyethylene glycol recombinant interferon (PEG-CIFN) which may be more effective and safer. Objective: to explore and evaluate the tolerance and early efficacy of polyethylene glycol recombinant integrated interferon (PEG-CIFN) in patients with chronic hepatitis C (CHC), so as to lay a foundation for the development of a safer and more effective interferon. Methods: 48 patients with chronic hepatitis C took part in the phase I clinical trial of PEG-CIFN. They were randomly divided into five groups: PEG-CIFN1.0 渭 g/kg (10 cases), PEG-CIFN1.5 渭 g/kg (10 cases), PEG-CIFN2.0 渭 g/kg (9 cases) and PEG-CIFN3.0 渭 g/kg (10 cases). PEG-IFN 伪 -2a (Pyloxin 180 渭 g / time) was used as the positive control group. The PEG-CIFN3.0 渭 g/kg group was administered for 4 weeks, and the drug tolerance was observed only several times. The other four groups were given subcutaneously once a week for a total of 14 weeks, and were not used to collect pharmacokinetic blood samples at week 2 and week 14. Symptom observation and laboratory examination were performed once a week to monitor adverse reactions and adjust dosage. HCV RNA quantitative and related safety indexes were measured at 0 weeks, 4 weeks, 8 weeks and 14 weeks. Results: none of the subjects had suspended the study. The drug tolerance was better in PEG-CIFN group (PEG-CIFN1.0,1.5,2.0 渭 g/kg) than in PEG-IFN 伪 -2a group (Piroxin group). PEG-CIFN1.5 渭 g/kg group, PEG-CIFN2.0 渭 g/kg group, and PEG-IFN 渭 g/kg group, the effect of platelet reduction was more moderate than that of PEG-IFN 伪 -2a group, PEG-CIFN2.0 渭 g/kg group, PEG-CIFN1.5 渭 g/kg group, PEG-CIFN2.0 渭 g/kg group, and PEG-CIFN1.5 渭 g/kg group. The "RVR" of PEG-CIFN3.0 渭 g/kg group and PEG-IFN 伪 -2a 180 渭 g group were 70% (7 / 10), 77.8% (7 / 9), 60% (6 / 10) and 77.8% (77.8%), respectively. The RVR of PEG-CIFN1.0 渭 g/kg group was only 10% (1 / 10). PEG-CIFN1.0 渭 g/kg group, PEG-CIFN1.5 渭 g/kg group, PEG-CIFN1.0 渭 g/kg group, PEG-CIFN1.5 渭 g/kg group, PEG-CIFN1.0 渭 g/kg group, PEG-CIFN1.5 渭 g/kg group. The "eRVR" of PEG-CIFN2.0 渭 g/kg group and PEG-IFN 伪 -2a180 渭 g group were 10% (1 / 10), 70% (7 / 10), 77.8% (7 / 9), respectively. The "early response rate" ("EVR") of PEG-CIFN1.0 渭 g/kg group, PEG-CIFN1.5 渭 g/kg group, PEG-CIFN2.0 渭 g/kg group and PEG-IFN 伪 -2a180 渭 g group was 30% (3 / 10), 90% (9 / 10), respectively. 88. 8% (8 / 9), 88. 8% (8 / 9). Conclusion: the patients with hepatitis C can tolerate PEG-CIFN in each dose group (1.0 ~ 1.5 渭 g/kg, 2.0 渭 g/kg). The virological response rate of PEG-CIFN1.5,2.0 渭 g/kg group is similar to that of PEG-IFN 伪 -2a group, and there is no significant difference between PEG-CIFN1.5,2.0 渭 g/kg group and PEG-IFN 伪 -2a group. In general, PEG-CIFN1.5 渭 g/kg can be used as clinical recommended dose. The efficacy of PEG-CIFN is dose-dependent. PEG-CIFN may have a better effect on type 1b HCV infection. At week 4, week 8, week 14, PEG-CIFN could maintain platelet level better than PEG-IFN 伪-2a.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R512.63

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