比較elbasvir/grazoprevir和ombitasvir/paritaprevir/ritonavir於慢性HCV genotype 1感染病人的有效性與安全性

Comparison of effectiveness and safety for the treatment elbasvir/grazoprevir and ombitasvir/paritaprevir/ritonavir in patients with chronic hepatitis C genotype 1 infection

洪瑄佑(Hsuan-Yu Hung)

指導教授 ： 陳崇鈺

高雄醫學大學/藥學院/藥學系碩士在職專班/碩士(2019年)

摘要

研究背景：
C型肝炎(Hepatitis C virus, HCV)基因型第1型是目前最為盛行的，自 2011年起，美國食品及藥物管理局(Food and drug administration, FDA)陸續核准新治療藥物機轉-直接抗病毒(direct-acting antiviral, DAA)，為口服劑型增加病患服藥順從性，其治癒率可達9成以上，本研究介入藥物Ombitasvir（OBV）為NS5A抑製劑，與paritaprevir（PTV）和ritonavir（r）-HCV NS3 / 4A蛋白酶抑製劑，合併使用dasabuvir（DSV）- NS5B聚合酶抑製劑； Elbasvir（EBR）為HCV NS5A抑製劑，與grazoprevir（GZR）-HCV NS3 / 4A蛋白酶抑製劑，根據疾病考量選擇是否合併ribavirin（RBV）治療。
目的
比較EBR / GZR和OBV / PTV / r + DSV於慢性HCV genotype 1感染病人的有效性與安全性, 有效性主評估治療後第12週持續病毒學反應(sustained virological response,SVR12)和復發比率，安全性主評估治療期間藥物引起肝損傷(drug-induced liver injury , DILI)不良事件。
研究方法
於戴德森醫療財團法人嘉義基督教醫院，以病歷回溯法 (A retrospective case-control study) 觀察院內就醫記錄，確診為HCV genotype 1感染病人，投予藥物OBV/PTV/r + DSV± RBV和EBR/GZR± RBV治療12或24週，估比較二組治療藥物的有效性和安全性。
結果
自2016年4月1日起至2018年8月31日止，共納入254名病人OBV/PTV/r + DSV± RBV (N=149) and EBR/GZR ± RBV (N=105) OBV/PTV/r + DSV ± RBV組中有8 (5.37%)名HCV genotype 1a，其他246 (96.85%)名皆為HCV genotype 1b， OBV/PTV/r + DSV 和EBR/GZR 治療慢性C型肝炎，整體有98.82% 達到SVR12，OBV/PTV/r + DSV ± RBV 99.33% (103/105)，EBR/GZR ± RBV組98.1% (148/149) 達到SVR12，OBV/PTV/r + DSV ± RBV組149人中有1 (0.67%) 人復發，EBR/GZR ± RBV組中105人中有2 (1.9%) 人復發；經回診檢驗值觀察到，共9 (3.54%)人發生DILI不良事件，OBV/PTV/r + DSV ± RBV組3 (2.01%) 人，EBR/GZR ± RBV組6 (5.71%) 人。
討論
使用EBR/GZR造成DILI不良事件的發生率比值(IRR)是OBV/PTV/r + DSV的2.84倍 (0.71-11.35) , P值=0.14，二者無顯著性差異。在次分組分析中，OBV/PTV/r + DSV ±RBV組女性有效好的治癒率，EBR/GZR ± RBV組則相反；曾經使用過IFN和RBV治療HCV病人，服用GZR / EBR治愈率較低。
結論
全民健康保險藥品支付價格相同，有效性和安全性二者皆無顯著性差異，治療過程中發生DILI不良事件，不影響藥物對疾病的治癒率；當醫病共決時，本研究真實世界數據可以提供作為藥物選擇之參考。

關鍵字

C型肝炎 ； HCV ； viekirax ； zepatier ； DILI

並列摘要

Background
Hepatitis C virus (HCV) genotype 1 is the most prevalent individuals worldwide. Since 2011, Food and Drug Administration (FDA) approved the new therapeutic drug: direct-acting antiviral (DAA). Ombitasvir (OBV)－an NS5A inhibitor, coformulated with paritaprevir (PTV) and ritonavir (r), an HCV NS3/4A protease inhibitor, and dasabuvir (DSV)－an NS5B polymerase inhibitor. Elbasvir(EBR)－an HCV NS5A inhibitor, coformulated with grazoprevir(GZR), an HCV NS3/4A protease inhibitor. It’s combination with or without ribavirin (RBV) to improve treatment.
Objective
To compare the effectiveness and safety of EBR/GZR and OBV/PTV/r +DSV in patients with HCV genotype 1 infection. The evaluation effectiveness were the proportion of patients with post-treatment virological relapse and sustained virological response at post-treatment week 12 (SVR12), the event of safety was associated with drug-induced liver injury (DILI).
Methods
The study was a retrospective case-control study at Ditmanson Medical Foundation Chia - Yi Christian Hospital in Taiwan. In this observational study of effectiveness and safety, patients with HCV genotype1 infection were received EBR/GZR ± RBV and OBV/PTV/r +DSV± RBV for 12 or 24 weeks. The primary effectiveness outcome were SVR12 (HCV RNA<15 IU/mL) and relapse .The primary safety outcome was the events occurred during treatment.
Results
Between April 01, 2015 and August 31, 2016, the study enrolled 254 patients of OBV/PTV/r + DSV± RBV (N=149) and EBR/GZR ± RBV (N=105), that 8 (3.15%) had genotype 1a HCV infection and 246 (96.85%) had genotype 1b infection. The Patients received treatment GZR/EBR± RBV and OBV/PTV/r + DSV± RBV for 12 or 24weeks, 98.10% (103/105) and 99.3% (148/149) achieved SVR12, with 2 (1.90%) and 1 (0.67%) relapse at post-treatment, respectively. We recorded 9 (3.54%) adverse events, of whom 6(5.71%) for GZR/EBR and 3 (2.01%) for OBV/PTV/r + DSV.
Discussion
Incidence rate ratio of GZR/EBR compare to OBV/PTV/r +DSV was 2.84, there were no significant difference. In Subgroup analysis, the female of OBV/PTV/r achieved SVR12 up to100%, GZR/EBR was the opposite. The treatment-experienced patients of IFN and RBV, had weak cure rate with GZR/EBR.
Conclusions
There were no significant difference in payment price, effectiveness and safety. In treatment period, even DILI adverse events incidenced but it not affect the cure rate for HCV infections. Real world data can provide as a reference, when the doctor and patient to decide on medication together.

並列關鍵字

Hepatitis C ； HCV ； viekirax ； zepatier ； DILI

參考文獻

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