AASLD 2013: PegInterferon Lambda 聚乙二醇干扰素拉姆达

StephenW

TITLE: Safety Profile of Peginterferon Lambda for Treatment of Chronic Hepatitis B (CHB) or Chronic
Hepatitis C (CHC): Cross-Study Analysis of Patients Treated in Three Phase 2 Studies
AUTHORS (FIRST NAME, LAST NAME): Andrew J. Muir1, Claire Jurkowski2, Elizabeth L. Cooney2, Jan L. Hillson3, Max Lataillade2, Veronica Mas Casullo2, Todd Gray3, Dong Xu2, Logesvaran Yogendran2, Subasree Srinivasan2
Institutional Author(s):
INSTITUTIONS (ALL): 1. Duke Clinical Research Institute, Duke University, Durham, NC, United States.
2. Research and Development, Bristol-Myers Squibb, Wallingford, CT, United States.
3. Bristol-Myers Squibb/ Zymogenetics, Seattle, WA, United States.
ABSTRACT BODY: Background
Peginterferon lambda-1a (Lambda) is a Type III interferon with limited extra-hepatic receptor distribution, which may result in fewer adverse events (AEs) than peginterferon alfa (Alfa). Lambda 180 µg weekly demonstrated more rapid early viral suppression than Alfa in patients with CHB and CHC. We present an integrated analysis of safety data for Lambda 180 µg weekly for 24-48 weeks in non-cirrhotics from all 3 Lambda phase 2 studies.

Methods
Available on-treatment safety data from non-cirrhotic patients who received Lambda monotherapy; Lambda plus ribavirin (RBV); or Lambda, RBV and a direct-acting antiviral (asunaprevir [ASV] or daclatasvir [DCV]) were grouped by regimen and compared with Alfa/RBV. Patients received Lambda monotherapy for CHB; all others were treated for CHC. Differences > 2-fold between groups are considered clinically significant.

Results
Analyses included 511 patients in 5 groups (table). Overall, 60% were male. Among CHB patients, mean age was 36 years, 89% were Asian, and mean baseline alanine aminotransferase (ALT) was 154 U/L. Among CHC patients, mean age across the 4 groups ranged from 46-48 years; 83% were white, 7% black/African American; and mean baseline ALT across the 4 groups ranged from 67-90 U/L. Fatigue was comparable across all groups (24%-46%); insomnia, asthenia, myalgia, arthralgia, rash, irritability, and decreased appetite were less frequent (<2-fold) with Lambda monotherapy (for CHB) compared to Lambda/RBV or Alfa/RBV (for CHC). Myalgia, arthralgia, chills, and pyrexia were less frequent with Lambda/RBV than with Alfa/RBV. Incidence of elevated ALT and elevated AST were more frequent with Lambda monotherapy and Lambda/RBV/ASV than with Alfa/RBV. Grade 3-4 laboratory abnormalities in hemoglobin, leukocytes, lymphocytes, platelets, and neutrophils were less frequent with Lambda-containing regimens than with Alfa/RBV. In Lambda-containing regimens, grade 3-4 ALT elevations were more frequent with CHB than CHC; grade 3-4 total bilirubin elevations were more frequent with CHC than CHB. Details of hepatic safety will be presented.

Conclusions
Lambda 180 µg once weekly/RBV for CHC is associated with significantly fewer hematologic abnormalities but higher rates of hepatic abnormalities than Alfa/RBV. Lambda monotherapy for CHB is associated with lower rates of systemic AEs than Lambda/RBV for CHC. Lambda is a better tolerated interferon than Alfa with a differentiated safety profile.

StephenW

StephenW

背景
聚乙二醇干扰素λ- 1A （拉姆达），是有限的肝外受体分布III型干扰素，这可能会导致更少的不良事件（AE ）比聚乙二醇干扰素α （阿尔法） 。拉姆达180微克每周展现更快速的早期病毒抑制CHB和CHC患者比阿尔法。我们提出的Lambda 180微克每周24-48周非肝硬化3拉姆达第2阶段研究的安全性数据的综合分析。

方法
可在治疗的安全性数据从非肝硬化患者谁收到拉姆达单药治疗; LAMBDA加利巴韦林（ RBV ）或Lambda ，利巴韦林和直接作用的抗病毒药物（ asunaprevir [ ASV ]或daclatasvir的DCV ）进行分组方案和比较阿尔法/ RBV 。患者接受单药治疗慢性乙型肝炎的Lambda CHC对待所有的人。 > 2倍组之间的差异被认为是临床意义。

结果
分析包括5组511例（表） 。总体而言，60％为男性。在慢性乙肝患者中，平均年龄为36岁， 89％是亚洲人，平均基线丙氨酸转氨酶（ALT）为154 U / L。在丙肝患者中，平均年龄从46-48岁不等跨4组， 83 ％是白人， 7 ％的黑人/非裔美国人和跨4组介乎67-90 U / L ，平均基线ALT疲劳与跨组（ 24 ％-46 ％ ） ，失眠，乏力，肌痛，关节痛，皮疹，烦躁，食欲下降那么频繁（ <2倍），与拉姆达单药治疗（ CHB ）相比， λ/ RBV阿尔法/ RBV （ CHC ） 。肌痛，关节痛，畏寒，发热拉姆达/ RBV比阿尔法/ RBV那么频繁。拉姆达单药治疗和Lambda / RBV / ASV比阿尔法/ RBV更频繁的发病率升高的ALT和AST升高。 3-4级实验室异常血红蛋白，白细胞，淋巴细胞，血小板和中性粒细胞减少频繁的Lambda含方案比阿尔法/ RBV 。 3-4级ALT升高的Lambda含方案，更频繁与CHB比CHC 3-4级总胆红素升高的慢性丙肝比CHB更频繁。肝脏安全的详细信息将提交。

结论
每周一次的Lambda 180微克/ RBV CHC伴有显着更少的血液异常，但较高的肝功能异常率比阿尔法/ RBV 。拉姆达单药治疗慢性乙型肝炎伴有全身不良率较低，比λ/ RBV为CHC 。 Lambda是一个更好的耐受性比阿尔法干扰素与差异化的安全性。

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