Telaprevir Not Cost Effective in All Patients With HCV Neil Canavan

StephenW

• The Liver Meeting 2011: American Association for the Study of Liver Diseases (AASLD) 62nd Annual Meeting
  

This coverage is not sanctioned by, nor a part of, the American Association for the Study of Liver Diseases.

From Medscape Medical NewsTelaprevir Not Cost Effective in All Patients With HCV

Neil Canavan

December 6, 2011 (San Francisco, California) — The recently approved and highly effective hepatitis C virus (HCV) protease inhibitor  telaprevir was shown not to be cost effective for the treatment of patients with HCV genotype 1 and the (CC) interleukin (IL)-28B  polymorphism, a genetic variant that predicts a favorable response to treatment with the standard dual regimen of pegylated interferon (peginterferon) and ribavirin.
This cost analysis was reported here at The Liver Meeting 2011: American Association for the Study of Liver Diseases (AASLD) 62nd Annual Meeting.
"IL-28B is the strongest pretreatment predictor of sustained virologic response in genotype 1 patients," said study presenter Ziad Gellad, MD, MPH, from the Department of Medicine–Gastroenterology, Duke University Medical Center, Durham, North Carolina. "In genotype 1 patients with the favorable (CC) IL-28B polymorphism, dual therapy with peginterferon and ribavirin is effective in the majority of patients."
That said, telaprevir in combination with peginterferon plus ribavirin has demonstrated significantly increased sustained viral response rates, compared with peginterferon plus ribavirin alone in phase 3 studies of treatment-naive and treatment-experienced genotype 1 patients with HCV.
Dr. Gellad asked: Is the addition of telaprevir cost effective in the subpopulation of patients with IL-28B (CC)? The answer, he said, is no.
"One of the potential benefits of tailoring therapy is decreasing cost," Dr. Gellad said. The current wholesale cost of the 2-drug regimen is $18,336 at 24 weeks and $36,672 at 48 weeks; for the 3-drug regimen, the cost is $67,536 at 12 weeks and $85,872 at 36 weeks.
Because the addition of telaprevir more than doubles the cost of treatment, Dr. Gellad designed a cost-effectiveness model to determine whether the added expense is really worth it for a patient with the favorable genotype 1 (CC) IL-28B profile.
The model is based on a number of assumptions: that societal perspective is limited, that no patients would have a coinfection with other viruses that accelerate liver-related death or prevent treatment, "and importantly,  that nonresponders or relapsers after dual therapy are retreated with a 48-week course of telaprevir."
The researchers developed a decision model that evaluated 3 treatment strategies:

• peginterferon plus ribavirin for 48 weeks, with a 12-week stopping rule for nonresponse; patients who did not respond or who relapsed would be treated with telaprevir
• a response-guided treatment approach with peginterferon plus ribavirin, in which those who achieved a rapid viral response (undetectable at week 4) would receive 24 weeks of dual therapy alone, and those with still-detectable viral loads at week 4 were treated for 48 weeks; nonresponsive or relapsed patients received telaprevir.
• 12 weeks of telaprevir in combination with 24 or 48 weeks of peginterferon plus ribavirin based on the extended rapid virologic response.
  

Treatment outcomes generated by the model were based on outcomes data derived from the IDEAL, REALIZE, and ADVANCE clinical trials.
A theoretical cohort of patients with 10,000 iterations was performed. The end point assumed 1 of 2 health states: sustained virologic response (cure) or fibrosis progression. Dr. Gellad's team assessed the cost of each. "As patients progressed through the model, they accumulated costs, which were expressed in [quality-adjusted life-years]," Dr. Gellad explained.
"The key point is that the efficacy of all 3 strategies is similar, but when you consider point estimates, telaprevir is dominated by the interferon/ribavirin strategies, and this preference is driven by the cost of therapy," Dr. Gellad told Medscape Medical News.
Costs generated by the model were $46,785 for peginterferon plus ribavirin given as response-guided therapy, $54,931 for peginterferon plus ribavirin (not response-guided), and $68,788 for telaprevir plus  peginterferon plus ribavirin.
"We then investigated the impact of the cost of telaprevir on the probability of cost effectiveness, and assumed a weekly cost of $3321 [the current cost of the drug].... If the cost dropped below $1433, a triplet with telaprevir became the preferred strategy," he reported.
Dr. Gellad concluded that in treatment-naïve patients with HCV genotype 1 and the (CC) IL-28B  polymorphism, initial therapy with a telaprevir-based regimen is unlikely to be cost effective under current cost and efficacy conditions.
                        Comparison Shopping                    
"What this group from Duke did is very important because, with resources dwindling, we need to figure out whether a particular treatment is more cost effective than another," said AASLD president T. Jake Liang, MD, tenured senior investigator and chief of the Liver Diseases Branch at the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland. "This is somewhat related to so-called personalized medicine because it uses a genetic marker to identify patients who will respond well to a certain treatment."
Major genetic studies conducted over the past several years have indicated that (CC) IL-28B  is a genetic marker highly associated with treatment response to interferon-based therapy. "This is a great marker — probably the best genetic marker we have so far — to gauge how a person will respond to treatment," Dr. Liang said.
The analysis by Dr. Gellad's team "suggests that this could be a way to save some money for patients with the favorable IL-28B genotype," he noted. Certainly, there is excitement about the recent availability of direct-acting antivirals, such as telaprevir, which greatly enhance treatment response, "but then again, maybe not one size fits all. In the spirit of personalized medicine, this may be one way we can reduce costs and, at the same time, retain the same success rate treating patients with HCV."
                        Dr. Gellad reports consulting for Merck & Co and receiving grants or research support from Merck & Co and PENTAX Medical. Dr. Liang has disclosed no relevant financial relationships.                    
The Liver Meeting 2011: American Association for the Study of Liver Diseases (AASLD) 62nd Annual Meeting. Abstract 118. Presented November 7, 2011.

StephenW

Telaprevir不符合成本与丙型肝炎患者有效

尼尔Canavan


2011年12月6日（加利福尼亚州旧金山市） - 最近批准的成本和高效的C型肝炎病毒（HCV）蛋白酶抑制剂telaprevir是不被有效地为患者治疗丙型肝炎病毒基因型1和白细胞介素（CC）（白细胞介素）- 28B的多态性，遗传变异，预测与聚乙二醇干扰素（聚乙二醇）和利巴韦林的双重标准方案治疗的反应良好。

这个成本分析报告肝会议2011年美国肝病研究协会（AASLD）第62届年会在这里。

“IL - 28B基因1型患者的持续病毒学应答最强的预处理预测说，”研究主持人齐亚德Gellad，医学博士，公共卫生硕士，消化内科医学部，北卡罗莱纳州杜克大学医学中心，达勒姆。 “有利（CC）的IL - 28B基因多态性，与聚乙二醇干扰素和利巴韦林双治疗基因1型患者在多数患者有效。”

这就是说，在telaprevir与聚乙二醇干扰素联合利巴韦林的组合已经证明明显增加持续病毒应答率相比，聚乙二醇干扰素联合利巴韦林仅在第一阶段3天真的治疗和治疗经验丰富的基因1型丙型肝炎患者研究。

Gellad博士问：是telaprevir成本除了有效地与IL - 28B（CC）的患者亚群？答案，他说，没有。

“剪裁治疗的潜在好处之一是降低成本，Gellad博士说。” 2药物治疗目前批发价格是$一万八千三百三十六在24周和48周36672元; 3，药物治疗，费用为67536在12周和36周85872元。

因为telaprevir除了增加了一倍以上的治疗费用，博士Gellad设计了一个符合成本效益模型，以确定增加的费用是否真的值得病人的有利基因型（CC）的IL - 28B剖面。

该模型是基于多项假设：是有限的，社会的角度来看，没有病人将有一个与其他病毒混合感染，加速肝脏有关的死亡或预防治疗“和重要的是，双治疗后无反应或relapsers撤退一个telaprevir 48周的课程。“

研究人员开发的决策模型评估3治疗策略：

    聚乙二醇干扰素联合利巴韦林48周，每周12停止对无应答的规则，谁没有回应或复发的患者，将被视为与telaprevir
    响应制导与聚乙二醇干扰素加病毒唑，治疗的方法，其中那些实现了快速的病毒反应（4周时检测不到）将单独收到的双重治疗24周，4周时仍检测的病毒载量的处理48周;无响应或复发的患者接受telaprevir。
    telaprevir 12周，在24或48周的聚乙二醇干扰素加利巴韦林的组合的基础上扩展快速病毒学应答。

模型所产生的治疗结果的基础上从理想的成果数据，实现，并推动临床试验。

万迭代理论的患者队列。终点假设1：2健康状态的持续病毒学应答（治愈）或纤维化的进展。 Gellad博士的研究小组评估每项成本。 “由于病人通过模型的进展，他们积累了成本，这是在[质量调整生命年表示，”Gellad博士解释说。

“关键的一点是，所有3个战略的疗效相似，但是当你考虑的点估计，telaprevir干扰素/利巴韦林战略为主，而这种偏好是治疗成本的驱动，”Gellad博士向Medscape医学新闻。

模型所产生的费用四六七八五聚乙二醇干扰素加利巴韦林作为响应，指导治疗，聚乙二醇干扰素加利巴韦林54931美元（不响应制导），和telaprevir加聚乙二醇干扰素联合利巴韦林68788美元。

“然后，我们调查的telaprevir对成本效益的概率成本的影响，并承担了每周3321美元的成本，目前的药物成本]....如果成本下降1433元以下的，三重与telaprevir成为首选的策略，他报告。“

Gellad博士的结论是，在治疗过的患者HCV基因型1和IL - 28B的多态性（CC），与telaprevir为基础的方案的初步治疗是不太可能的成本目前的成本和有效性条件下的有效。

比较购物

这一群来自杜克大学是非常重要的，因为随着资源日益减少，我们需要找出一个特定的治疗是否是更多的成本比另一个有效，肝病学会主席T.杰克梁医师说：“终身高级研究员和行政肝病科在国立糖尿病，消化道和肾脏疾病，马里兰州贝塞斯达国家卫生研究院。 “这是有点关系，以所谓的个性化的医药，因为它使用了一个遗传标记，以确定谁将一定的治疗反应良好的病人。”

在过去几年中进行的主要遗传研究表明，（CC）的IL - 28B是一种高度与治疗反应干扰素治疗相关的遗传标记。 “这是一个伟大的的标记 - 可能是最好的遗传标记到目前为止，我们已 - 来衡量一个人将如何响应处理，梁医生说。”

Gellad博士的研究小组分析“表明，这可能是有利的IL - 28B基因型患​​者的方式来保存一些钱，”他说。当然，也有直接作用的抗病毒药物，如telaprevir，从而大大提高治疗的反应，最近推出的兴奋，“不过话又说回来，也许没有一个放之四海而皆准的个性化医疗的精神，这可能是单程我们可以降低成本，同时，保留了同样的成功率，治疗丙型肝炎患者。“

Gellad博士报告咨询默克公司和默克公司和宾得医疗接收赠款或研究的支持。梁医生已宣告没有相关财务关系。

肝会议2011年美国肝病研究协会（AASLD）第62届年会。摘要118。发表，2011年11月7日。