新药跟踪: 长效干扰素治疗乙肝

liver411

(请有时间的朋友帮忙翻译, 谢谢)


Treatment of Chronic Hepatitis B with Pegasys Shows Improved Response Rate Compared to Roferon

By Mack Mitchell, MD

Although much of the recent attention has been focused on nucleoside analogues for treatment of chronic hepatitis B, interferon remains an alternative therapy.

Patients and physicians have generally resisted use of interferons because of expense, side effects and the fact that it must be administered by injection. Furthermore, standard interferon dosing regimens were not very effective in producing HBeAg seroconversion in patients with low ALT and high HBV DNA levels.

The advent of the pegylated interferons has simplified treatment to a once weekly injection regimen that appears to have somewhat fewer side effects than the high dose (5 MU) daily injections of interferon alfa.

Cooksley and his colleagues reported on the use of 40 kDa pegylated a-interferon 2a (Pegasys) for treatment of HBeAg positive CHB. Patients were given weekly injections of 90, 180 or 270 µg of Pegasys or 4.5 million units three of interferon a2a, three times weekly for a total of 24 weeks.

At the end of an additional follow-up period of 24 weeks, 24% of patients treated with Pegasys had lost HBeAg, normalized ALT and suppressed HBV DNA to < 500,000 copies/ml (Roche Amplicor assay) compared with 12% of those treated with standard a-interferon 2a (p < .05).

Subset analysis indicated that patients with ALT > 5 x ULN had the highest rates of HBeAg loss, suppression of HBV DNA and normalization of ALT (29%), with similar results for both Pegasys and interferon alfa-2a. However, patients with ALT 2-5 x ULN and < 2 x ULN derived more benefit when treated with Pegasys compared with the standard interferon.

The combined response of HBeAg loss, HBV DNA suppression and normalization of ALT occurred in 27% vs 11% for ALT < 2 x ULN and 22% vs 7% for ALT 2-5 x ULN for Pegasys-treated patients. A similar observation of improved efficacy was noted in those patients with high DNA levels.

Several points are worth noting about these findings.

Although statistical significance was not achieved in the subset analyses because of relatively small numbers, the results are intriguing. There is a clear suggestion that those patients who are traditionally most resistant to treatment (high DNA levels and low ALT) are the ones who will benefit the most from pegylated interferon. This is an important observation if it holds up since there are many patients who fall into this category and were previously not believed to be good candidates for lamivudine or standard interferon dosing because of lack of efficacy.

Although seroconversion to HBeAb was not reported, the loss of HBeAg and ALT normalization was relatively high (comparable to nucleoside analogues). Presumably, as reported with other studies of interferon treatment in CHB, seroconversion to HBeAb may be delayed for up to 1 year after completion of therapy.

It was somewhat surprising that suppression of HBV DNA to < 500,000 copies was used as an endpoint, since most recent studies of adefovir and other nucleoside analogues have used detection limits of < 400 copies/ml as an endpoint.

01/08/03

Reference
WG Cooksley and others. HBeAg-POSITIVE CHRONIC HEPATITIS B (CHB) PATIENTS WITH DIFFICULT-TO-TREAT DISEASE: IMPROVED RESPONSE RATES WITH PEGINTERFERON ALFA-2a (40KD) (PEGASYS&reg;) COMPARED WITH CONVENTIONAL INTERFERON ALFA-2A. Abstract 846. 53rd AASLD. Boston, November 1-5, 2002. Hepatology Vol 36, No 4, Part 2 of 2. October 2002.


(内部交流)

liverbj

我来翻译这段吧。

liverbj

Treatment of Chronic Hepatitis B with Pegasys Shows Improved Response Rate Compared to Roferon Pegasys 相对于 Roferon对治疗慢性乙肝显示出更高的应答率 By Mack Mitchell, MD Although much of the recent attention has been focused on nucleoside analogues for treatment of chronic hepatitis B, interferon remains an alternative therapy. 虽然最近非常多的注意力被集中到核苷类似物治疗乙肝的方面来，但是干扰素仍然还是一种可供选择的治疗方法。 Patients and physicians have generally resisted use of interferons because of expense, side effects and the fact that it must be administered by injection. Furthermore, standard interferon dosing regimens were not very effective in producing HBeAg seroconversion in patients with low ALT and high HBV DNA levels. 患者和医生通常都由于价格问题、副作用以及它必须经过注射而反对使用干扰素。另外，标准计量的干扰素给药对那些低水平ALT和高HBVDNA的 患者在产生e抗原血清转换上不是很有效果。 The advent of the pegylated interferons has simplified treatment to a once weekly injection regimen that appears to have somewhat fewer side effects than the high dose (5 MU) daily injections of interferon alfa. 长效干扰素？（pegylated interferons)的出现简化了治疗，一周注射一次显示出比每天注射高剂量的阿拉法干扰素有较低的副作用。 Cooksley and his colleagues reported on the use of 40 kDa pegylated a-interferon 2a (Pegasys) for treatment of HBeAg positive CHB. Patients were given weekly injections of 90, 180 or 270 µg of Pegasys or 4.5 million units three of interferon a2a, three times weekly for a total of 24 weeks. Cooksley和他的同事报告说使用40kDA pegylated a-interferon 2a(Pegasys)来治疗e抗原阳性的慢性乙肝。患者们每周注射90，180或 270微克的Pegasys或者四百五十万单位的3个干扰素a2a， 每周三次，一共24周。 At the end of an additional follow-up period of 24 weeks, 24% of patients treated with Pegasys had lost HBeAg, normalized ALT and suppressed HBV DNA to < 500,000 copies/ml (Roche Amplicor assay) compared with 12% of those treated with standard a-interferon 2a (p < .05). 在接下来的另外一个24周的最后，24％的使用Pegasys的患者e抗原检测不到，ALT变为正常，HBV DNA降为小与500，000拷贝／毫升(Roche Amplicor检测）相对于12％的那些使用标准a-干扰素 2a的患者（P<.05） Subset analysis indicated that patients with ALT > 5 x ULN had the highest rates of HBeAg loss, suppression of HBV DNA and normalization of ALT (29%), with similar results for both Pegasys and interferon alfa-2a. However, patients with ALT 2-5 x ULN and < 2 x ULN derived more benefit when treated with Pegasys compared with the standard interferon. 对子集的分析指出那些ALT>5 x ULN的患者e抗原转化率，HBV DNA减少和ALT（29％）正常化都是最好的，不管是使用Pegasys还是阿拉法－2a 干扰素。然而那些ALT在2－5 x ULN 和 <2 x ULN的患者相对于标准干扰素，更加得益于使用Pegasys. The combined response of HBeAg loss, HBV DNA suppression and normalization of ALT occurred in 27% vs 11% for ALT < 2 x ULN and 22% vs 7% for ALT 2-5 x ULN for Pegasys-treated patients. A similar observation of improved efficacy was noted in those patients with high DNA levels. 对使用Pegasys疗法的患者，其中ALT<2 x ULN的 e抗原转化，HBV DNA减少以及ALT正常的应答是22％比7％，ALT为2－5 x ULN的为22％比7 ％（应该是相对于使用标准干扰素）。同样的观测报告在那些有着高水平DNA的患者中也可以被注意到，但是有更高的效率。 Several points are worth noting about these findings. 关于这些发现有以下几点值得关注 Although statistical significance was not achieved in the subset analyses because of relatively small numbers, the results are intriguing. There is a clear suggestion that those patients who are traditionally most resistant to treatment (high DNA levels and low ALT) are the ones who will benefit the most from pegylated interferon. This is an important observation if it holds up since there are many patients who fall into this category and were previously not believed to be good candidates for lamivudine or standard interferon dosing because of lack of efficacy. 虽然在这次子集分析中由于相对少的数量并没什么统计学的意义，但是结果却是很吸引人的。很明确的建议是对那些对传统的疗法（高DNA水平和 低ALT）没有什么效果的患者将会从长效干扰素（Pegylated interferon）中获得最大的收益。如果这个观测报告能够持续的话那么它是非常 重要的。因为那些符合这个类型的患者非常多,他们以前由于低应答对拉米夫定和标准干扰素被认为无效， Although seroconversion to HBeAb was not reported, the loss of HBeAg and ALT normalization was relatively high (comparable to nucleoside analogues). Presumably, as reported with other studies of interferon treatment in CHB, seroconversion to HBeAb may be delayed for up to 1 year after completion of therapy. 虽然e抗原的血清转换没有报道，但是e抗原的减少和ALT正常化却相对较高（对比于核苷类似物）。可以推测，相对于其他慢性乙肝干扰素治疗的 研究，e抗原的血清转换将会在疗法结束后延迟至多一年。 It was somewhat surprising that suppression of HBV DNA to < 500,000 copies was used as an endpoint, since most recent studies of adefovir and other nucleoside analogues have used detection limits of < 400 copies/ml as an endpoint. HBV DNA减至<500,000拷贝是最终值有一点让人惊讶。因为大多数最近的关于阿德福伟和其他核苷类似物的研究表明<400拷贝／毫升是最终值。 01/08/03 Reference 参考 WG Cooksley and others. HBeAg-POSITIVE CHRONIC HEPATITIS B (CHB) PATIENTS WITH DIFFICULT-TO-TREAT DISEASE: IMPROVED RESPONSE RATES WITH PEGINTERFERON ALFA-2a (40KD) (PEGASYS®) COMPARED WITH CONVENTIONAL INTERFERON ALFA-2A. Abstract 846. 53rd AASLD. Boston, November 1-5, 2002. Hepatology Vol 36, No 4, Part 2 of 2. October 2002.

hchu

辛苦了！十二分的谢谢。
这一句十分振奋人心：

　“虽然在这次子集分析中由于相对少的数量并没什么统计学的意义，但是结果却是很吸引人的。很明确的建议是对那些对传统的疗法（高DNA水平和低ALT）没有什么效果的患者将会从长效干扰素（Pegylated interferon）中获得最大的收益。如果这个观测报告能够持续的话那么它是非常重要的。因为那些符合这个类型的患者非常多,他们以前由于低应答对拉米夫定和标准干扰素被认为无效。”

是不是说，肝功正常的携带者是不是可以治疗了？请高手们分析看看。