EASL 2018 PS-161 LOWR HDV-2研究的亚组分析揭示了高反应率 Lonafarnib

StephenW

EASL 2018 PS-161
Subanalysis of the LOWR HDV-2 study reveals high response rates
to Lonafarnib in patients with low viral loads
C. Yurdaydin1,2, C. Kalkan2, F. Karakaya2, A. Caliskan2, S. Karataylı2,
O. Keskin2, R. Idilman2, M. Bozdayı2, C. Koh3, T. Heller3, J. Glenn4.
1Gastroenterology, Turkey; 2Division of Gastroenterology, University of
Ankara Medical School, Turkey; 3Liver Diseases Branch, NIDDK; 4Division
of Gastroenterology and Hepatology and Department of Microbiology
and Immunology, Stanford University School of Medicine
Email: [email protected]
Background and Aims: The LOWR HDV-2 study explored multiple
combinations of LNF and RTV, with or without PEG-IFNα, for 12 to 48
weeks, in patients chronically infected with HDV. Antiviral responses
were observed in all treatment groups. Here we sought to analyze
response rates as a function of baseline viral loads (BVL) among
patients completing 24 weeks of the various LNF-based regimens.
Method: 33 patients completed 24weeks of the following LNF-based
regimens:
Group 1 (n = 14): LNF 50 mg BID + RTV 100 mg BID. This included 2
re-treatment patients, who had previously been treated with a short
oral course of LNF based therapy (LNF 200 mg BID or LNF 300 mg BID
for 12 weeks), and achieved HDV RNA negativity for 6 months,
followed by a return of HDV RNA to low BVL < 4 log; Group 2 (n = 6):
LNF 25 mg BID + RTV 100 mg BID; Group 3 (n = 4): LNF 50 mg BID +
RTV 100 mg BID + PEG-IFNα 180 micrograms QW; Group 4 (n = 5):
LNF 25 mg BID + RTV 100 mg BID + PEG-IFNα 180 micrograms QW;
Group 5 (n = 4): LNF 50 mg BID + RTV 100 mg BID + addition of PEGIFNα
180micrograms QW for weeks 12–24. 12 of 33 (36%) patients
had low BVL, defined as <4 logIU/ml and 21 of 33 (64%) patients had
BVL > 4 logIU/ml. HDV RNA was measured by validated RoboGene®
HDV RNA Quantification (LOQ: 14IU/ml; LOD 8IU/ml). Responders
were defined as patients achieving >2 log drop in HDV RNA (or BLOQ
for patients with BVL < 2 log) at the end of 24 weeks.
Results: 21 of 33 (64%) patients across all treatment groups were
responders at 24 weeks. For patients with BVL > 4 log, response rate
was 12 of 21 (57%). Response rate at 24 weeks for patients with low
BVL < 4 log was higher, 9 of 12 (75%), described below:
7 of 7 (100%) patients treated with all oral LNF 50 mg BID + RTV
100 mg BID (Group 1) were BLOQ (n = 2) or PCR-negative (n = 5) at 24
weeks, including the 2 re-treatment patients. 1 of 1 patients from
Group 4 and 1 of 1 patients from Group 5 became BLOQ at 24 weeks.
0 of 3 (0%) patients from Group 2were BLOQ at 24weeks. Group 3 had
no patients with low BVL
Conclusion: 6-month LNF-based regimens achieved virologic
responses in a majority of patients. All oral LNF 50 mg BID + RTV
100 mg BID appears to be particularly attractive for patients with low
BVL, as 100% of patients were responders. These results also suggest
that prolonged control of HDV may be achieved in appropriate
patients by 6-month pulse therapy with all oral LNF 50 mg BID + RTV
100 mg BID, in both LNF naïve and experienced patients.

StephenW

EASL 2018 PS-161
LOWR HDV-2研究的亚组分析揭示了高反应率
Lonafarnib适用于低充满活力的患者
C. Yurdaydin1,2，C.Kalkan2，F. Karakaya2，A. Caliskan2，S.Karataylı2，
O. Keskin2，R. Idilman2，M.Bozdayı2，C. Koh3，T. Heller3，J.Glenn4。
1土耳其的胃肠病学;胃肠病学，胃肠病学二级学科
土耳其安卡拉医学院; 3肝病科，NIDDK; 4Division
胃肠病学和肝病学以及微生物学系
和斯坦福大学医学院的免疫学
电子邮件：[email protected]
背景和目标：LOWR HDV-2研究探索了多个问题
LNF和RTV的组合，有或没有PEG-IFNα，12到48
在几周内，慢性感染HDV的患者。抗病毒反应
在所有治疗组中观察到。我们在这里试图分析
响应率与基线病毒载量（BVL）之间的函数
患者完成24周的各种基于LNF的方案。
方法：33例患者完成24周以下基于LNF的治疗
养生之道：
组1（n = 14）：LNF 50mg BID + RTV 100mg BID。这包括2
重新治疗的病人，曾经接受过短暂治疗
基于LNF治疗的口服疗程（LNF 200 mg BID或LNF 300 mg BID
对于12周），并实现6个月的HDV RNA阴性，
随后HDV RNA返回至低BVL <4log;第2组（n = 6）：
LNF 25毫克BID + RTV 100毫克BID;第3组（n = 4）：LNF 50mg BID +
RTV 100mg BID + PEG-IFNα180微克QW;第4组（n = 5）：
LNF 25mg BID + RTV 100mg BID + PEG-IFNα180微克QW;
第5组（n = 4）：LNF 50mg BID + RTV 100mg BID +加入PEGIFNα
第12-24周为180微克QW。 12/33（36％）患者
BVL低，定义为<4 logIU / ml，33例（64％）患者中有21例有BVL
BVL> 4logIU / ml。通过验证的RoboGene®测量HDV RNA
HDV RNA定量（LOQ：14IU / ml; LOD 8IU / ml）。急救员
被定义为在HDV RNA（或BLOQ）中达到> 2个对数级的患者
对于BVL <2 log的患者，在24周结束时。
结果：所有治疗组中33例（64％）患者中有21例为
24周的应答者。对BVL> 4 log的患者，有效率
21岁的人中有12人（57％）。对于低危患者，24周时的反应率
BVL <4log较高，12例中有9例（75％），如下所述：
7例（100％）接受全口服LNF 50 mg BID + RTV治疗的患者
100mg BID（第1组）在24时是BLOQ（n = 2）或PCR阴性（n = 5）
包括2名重新治疗的患者。 1名患者中1人来自
第5组的1位患者中的第4组和第1位在第24周时变成BLOQ。
第2组有3名（0％）患者在24周时出现BLOQ。第3组有
没有低BVL的患者
结论：6个月的基于LNF的方案达到了病毒学
对大多数患者的反应。所有口服LNF 50mg BID + RTV
低剂量患者100mg BID似乎不常见
BVL，因为100％的患者是应答者。这些结果也表明
HDV的长时间控制可能会达到
所有口服LNF 50 mg BID + RTV的6个月脉冲治疗患者
在LNF初始和有经验的患者中均为100mg BID。