丙型肝炎患者可能能够延迟使用三联疗法
2012-05-28 12:02:42   来源： 丁香园   作者：  评论：0 点击：

Hepatitis C patients without significant fibrosis may be able to delay triple therapy and wait for simpler, shorter, and potentially all-oral regimens that are currently under investigation, researchers said here.
研究人员说：没有出现明显纤维化的丙型肝炎患者可能能够延迟使用三联疗法，而等待使用目前处于研究状态的更加简单、疗程更短、有望全部口服的疗法。

The addition of new protease inhibitors telaprevir (Incivek) and boceprevir (Victrelis) to previous standard therapy of interferon and ribavirin have significantly boosted sustained viral response for many patients, especially for blacks and Latinos, according to Maribel Rodriguez-Torres, MD, of the Fundacion de Investigation in Rio Piedras, Puerto Rico.
Maribel Rodriguez-Torres说：在之前的干扰素和病毒唑标准疗法基础上增加新的蛋白酶抑制剂特拉匹韦（telaprevir，即Incivek）和 博赛泼维（boceprevir ，即Victrelis）显著地增加了大多数患者的病毒反应时间，尤其对黑人和拉丁裔患者效果更好。Maribel Rodriguez-Torres是波多黎各里奥彼德拉斯市Fundacion de Investigation的医学博士。

But patients with less severe disease may be able to hold off until a handful of newer agents -- offering less complex regimens that potentially cut the symptomatic interferon from the mix -- come to market, possibly within the next two years, Rodriguez-Torres said during a symposium at Digestive Disease Week (DDW) here.
在消化系统疾病周（Digestive Disease Week，缩写为DDW）的论坛上，Rodriguez-Torres说：病情不严重的患者可能能够拖延到一些更新的药物上市（上市时间可能在2年内）。这些药物参与组成的新疗法可以去除干扰素。

"This is a slowly progressing disease and most of the time we have the time and opportunity to determine what's the best [treatment strategy] for our patients," she said. "Patients without significant fibrosis should wait. Those with more advanced disease should consider therapy today."
她说：“这是一种进展缓慢的疾病，大多数情况下，我们有时间、也有机会分辨出哪种治疗策略是最好的。没有出现严重纤维化的肝炎病人应当等待，而症状比较严重的病人现在就应当考虑进行治疗。”

Triple Therapy Presents Challenges
三联疗法有挑战性

Clinicians have cited a number of challenges with triple therapy. Both new agents are only indicated for patients with genotype 1 disease -- though this comprises the majority of patients -- and they add a significant cost to treatment, Rodriguez-Torres said.
Rodriguez-Torres说：临床医师提出了三联疗法的很多问题。这两种成分（指蛋白酶抑制剂）的适应症都是基因型为1型的疾病——虽然这占了患者的绝大多数——并且使治疗成本显著增加。

The regimen is also complex and long-lasting, with both new agents adding multiple daily pills to ribavirin's four to six pills per day and weekly interferon injections, extending for 24 to 48 weeks.
这种疗法既复杂又耗时。使用这种疗法，需要日服病毒唑4到6片，每周注射一次干扰素，每天还要服用几片蛋白质抑制剂。这种疗法要持续进行24到48周。

There's also an increased risk of drug-drug interactions, as both new agents inhibit the common CYP34A metabolic pathway, potentially increasing levels of other drugs metabolized that way. That list includes some statins and ACE inhibitors, which "aren't unusual drugs," Rodriguez-Torres said.
药物相互作用的风险也会提高，因为两种药物都会抑制CYP34A代谢途径，可能增加了依赖该代谢途径降解的药物的水平。这些药物包括他汀类和血管紧张素酶抑制剂，这些药物“都是很常见的药物，” Rodriguez-Torres如是说。

Side effects include anemia, a concern because ribavirin already lowers blood hemoglobin levels, she said. Also, telaprevir appears to cause rash in more than 50% of patients.
她说：副作用有贫血症，这是值得关注的。因为病毒唑已经降低了血液中的血红蛋白浓度。另外，病毒唑好像能够在超过50%的患者中引起皮疹。

Instead, a "dream regimen" is a simple one with fewer pills, contains only oral agents, spans all genotypes, and is highly effective with an excellent safety and tolerability profile -- though that possibility is not that far from reality, Rodriguez-Torres said.
Rodriguez-Torres说：“梦想的疗法”是一种 简单的只需要服用很少药物的治疗方法。这种疗法包含的药物都是口服药，适用于各种基因型的病人，非常有效，安全性很好，耐受性良好。虽然这种可能性离现实 不是太远，但是“梦想的疗法”现在还是只存在于我们的想象中。

Improvements Are on the Horizon
改进正在慢慢进行

"We've never had such an explosion of drug development in the last 75 years compared to what we see now in chronic hepatitis C," she said. That robust pipeline includes not only a number of protease inhibitors and NS5A inhibitors -- which are typically genotype-specific -- but also nucleoside and cyclophilin inhibitors that are pan-genotypic.
我们现在慢性丙型肝炎的药物开发上的发展速度之快是过去75年中远远不及的。这些新药不仅包括大量的蛋白酶抑制剂和非结构蛋白5A(NS5A)抑制剂,这些药物是典型的基因型特异性药物，而且包括对各种基因型的患者都有效的核苷和亲环蛋白抑制剂。

Such robustness may help keep prices down as a result of increased competition, Rodriguez-Torres said. Also, the majority of drugs in development are dosed once or twice daily and some have a much shorter duration of therapy than the current standard of 24 to 48 weeks.
Rodriguez-Torres说：因为竞争的加剧，这么多药物的价格会出现下降。另外，大部分在研药物都是每日一次或者每日两次，有些药物的疗程比现在的典型疗程24到48周要短。

Early data also have shown that it's possible to drop interferon from the regimen. Last month at the European Association for the Study of the Liver meeting Barcelona, researchers reported that high proportions of patients has sustained virologic response rates with an all-oral regimen of ribavirin plus two investigational agents, ABT-450/r, a protease inhibitor, and ABT-072, a non-nucleoside NS5B polymerase inhibitor.
早 期数据显示：有可能将干扰素从治疗方法中去除。研究人员于上个月在巴塞罗那举办的欧洲协会的肝病研究会议上报告说：在对患者进行病毒唑和2种观察研究药物 的口服治疗后，大部分患者具有持久的病毒反应率。这两种观察药物是蛋白酶抑制剂 ABT-450/r和非核苷类NS5B聚合酶抑制剂ABT-072。

Also at that meeting, an early trial showed that a combination of daclatasvir, an NS5B inhibitor, plus GS-7977, a nucleotide NS5B inhibitor, led to rapid and sustained viral response in patients with genotypes 1-3, with or without ribavirin.
在那次会议上，早期研究显示：在服用或者不服用病毒唑的情况下，daclatasvir（NS5B抑制剂）和GS-7977(核苷酸类NS5B抑制剂)联合用药都能使基因型为1-3型的患者出现快速而持久的病毒反应。

Treatment Issues Remain Complex
治疗问题还是那么复杂

The pressing question facing clinicians, then, has been determining who to treat and when. Rodriguez-Torres said the simple answer is to treat those with severe fibrosis now, but hold off on treating those without significant fibrosis.
此外，临床医生面临的紧迫问题是治疗哪些患者，什么时候治疗。Rodriguez-Torres说：这个问题的简单回答是：现在就治疗出现严重纤维化的病人，以后治疗没有明显纤维化的病人。

But Andrew Muir, MD, clinical director of hepatology at Duke University, told MedPage Today the decision should rest largely with the patient.
不过，杜克大学肝病专科医疗主任、医学博士Andrew Muir告诉MedPage Today记者：采取什么样的治疗措施主要依赖于患者。

"I get concerned about us being too heavy handed deciding which patients should or should not get hepatitis C treatment," he said. "Our role should be to guide patients about potential options, and those discussions can take quite a bit of time."
他说：“我担心我们在决定哪些病人应该进行丙型肝炎病毒治疗时，过于**。我们的责任应该是指导患者进行各种选择，这些讨论会持续一段时间。”

He noted, however, that the side effects "will be much better for these patients with future therapies. But I have had patients elect to proceed with treatment even with early-stage disease. Some have felt it was the right time for them to proceed with treatment for a number of personal reasons. Some worried if they would have stable health insurance in the future."
不过，他提示说：“选择以后进行治疗的病人的”副作用“会更小。不过，我的一些病人即使处在疾病的早期阶段，还是选择马上进行治疗。有些人认为有很多理由支持他们马上进行治疗。有些人担心以后会不会有稳定的医疗保险（保证完成治疗）”。

On the other hand, Zobair Younossi, MD, of Inova Health System in Great Falls, Va., said some of his patients actually "warehouse themselves for regimens that do not include interferon."
另一方面，大瀑布城的爱诺华医疗系统的的医学博士Zobair Younossi说：事实上，有些病人“坚持等待接受不含干扰素的疗法”。

Muir also noted that even some advanced fibrosis patients may be eligible for watchful waiting, since not all of them will progress quickly.
Muir也提示说：即使一些严重纤维化病人也可能有足够的理由选择以后的疗法，因为不是每个严重纤维化病人的病程进展都很快。

"If the patient has great risks to treatment, or if the patient does not think the chance of response is good enough to take on the side effects, then delaying therapy is the right thing for that individual [advanced fibrosis] patient as well," he told MedPage Today. "If they do not take treatment, they must get aggressive about liver wellness. That means no alcohol, get in shape and lose weight if needed, and get tight control of your blood sugars if you have diabetes."
他告诉MedPage Today记者：“如果病人认为进行治疗具有很大风险，或者病人认为与必须承受的治疗风险相比，治疗效果还不够好，那么，对那些具有严重纤维化的病人来 说，推迟治疗也是非常合适的。如果这些病人不进行治疗，那么，他们必须充分保证肝脏健康。这意味着：不能饮酒，保持身体健康，根据需要进行减肥，如果有糖 尿病，还要严格控制血糖水平。”