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October 1, 2007 — 根据登载于10月1日内科医学档案期刊(Annals of Internal Medicine)的一项开放标签随机试验，Telbivudine看似比adefovir dipivoxil对慢性B型肝炎病毒(HBV)感染更有效。
香港中文大学的Henry L.Y. Chan医师和018研究小组的同事指出，核苷和核苷酸衍生物对B型肝炎的效果，与对HBV抑制的强度和持久性有关；Telbivudine和adefovir并未被直接比较，但在第3期试验中，使用telbivudine 1年后的HBV DNA降低效果看似大于同族群的adefovir报告结果。
本研究的目标是比较 telbivudine和adefovir dipivoxil对B型肝炎e抗原(HBeAg)阳性之慢性HBV感染病患的抗病毒效果，以及评估从adefovir转为telbivudine治疗的效果。
在16个门诊处的135位未治疗过之HbeAg阳性慢性HBV感染成人，以1:1:1 的比率随机指派接受 telbivudine (A组)、adefovir (B组)，或者使用24 周的adefovir，之后在最后的28周改用 telbivudine (C组)；主要终点是24周时的血清HBV DNA减少程度，次级终点是在第52周时再次进行比较；第52周时比较的病患数为131人。
24周的HBV DNA平均减少程度，A组大于B和C两组混合 (-6.30 vs -4.97 log10 copies/mL；差异，-1.33 log10 copies/mL; 95% 信心区间 [CI], -1.99 到 -0.66 log10 copies/mL; P < .001)；此外，A组中有较多病患在24周时的聚合酶链反应为阴性(39% vs 12%；风险比，4.46[95% CI, 1.86 – 10.72]; P = .001)。
第52周时，相较于持续使用adefovir者(B组)，持续治疗组(A组)、转换组(C组)之平均残余HBV DNA较低(3.01 log10 copies/mL [A组] ， 3.02 log10 copies/mL [C组] ， 4.00 log10 copies/mL [B组]；差异，-0.99 log10 copies/mL [95% CI, -1.67 到 -0.32 log10 copies/mL]， -0.98 log10 copies/mL [95% CI, -1.64 到 -0.32 log10 copies/mL]; P = .004)。
这3组的副作用相似；最常报告的是上呼吸道症状、头痛、背痛和腹泻。
作者指出，24周治疗后，Telbivudine比adefovir对HBV DNA抑制更强、更持续；第52 周之后，持续使用telbivudine者或者使用24周的adefovir 后改用telbivudine者的 HBV DNA抑制效果较大。
研究限制包括，这是开放标签设计；对比较临床结果和长期效果而言，样本和研究期间太短；一般性有限，因为所有病患都是 HbeAg阳性，且未用过核苷和核苷酸，以及几乎都是亚洲人。
作者结论表示，本研究的资料支持治疗初期病毒抑制效果越大，效果越有改善且阻抗性越低的观念，越可以在初期治疗提供更大的病毒抑制效果的制剂越好；本研究和之前的研究所提供的资料指出，telbivudine可以比adefovir和lamivudine提供更大的病毒抑制效果，随着常规监测以确认维持治疗反应，telbivudine在慢性B型肝型治疗处方将扮演重要角色。
有些作者报告有潜在的利益冲突，情况主要是受雇于一些药厂，例如诺华、Idenix Pharmaceuticals、Bristol-Myers Squibb、Canadian Health Protection Board、罗氏、Vertex、Schering-Plough、格兰素史克、Bristol-Myers Squibb、Gilead Sciences、惠氏、Human Genome Sciences和/或 Celera。
Ann Intern Med. Published online October 1, 2007.
Telbivudine May Be More Efficient for Chronic Hepatitis B Than Adefovir Dipivoxil
By Laurie Barclay, MD
Medscape Medical News
October 1, 2007 — Telbivudine appears to be a more efficient drug to treat chronic hepatitis B virus (HBV) infection than adefovir dipivoxil, according to the results of an open-label, randomized controlled trial published online October 1 in the Annals of Internal Medicine.
"The efficacy of nucleoside and nucleotide analogues for hepatitis B has been linked to the magnitude and durability of suppression," write Henry L.Y. Chan, MD, from the Chinese University of Hong Kong, and colleagues from the 018 Study Group. "Telbivudine and adefovir have not been compared directly, although HBV DNA reductions after 1 year of telbivudine in phase III trials seemed greater than those reported with adefovir in similar patient populations."
The goal of this study was to compare the antiviral efficacy of telbivudine and adefovir dipivoxil in hepatitis B e antigen (HBeAg)–positive patients with chronic HBV infection and to evaluate the effects of switching from adefovir to telbivudine therapy,
At 16 outpatient clinics, 135 treatment-naive, HBeAg-positive adults with chronic HBV infection were randomly assigned in a 1:1:1 ratio to telbivudine (group A), adefovir (group B), or 24 weeks of adefovir and then telbivudine for the remaining 28 weeks (group C). The main endpoint was serum HBV DNA reduction at week 24, and the secondary endpoint was the same comparison at week 52. The 52-week study was completed by 131 patients.
The mean decrease in HBV DNA at week 24 was greater in group A than in pooled groups B and C (−6.30 vs −4.97 log10 copies/mL; difference, −1.33 log10 copies/mL; 95% confidence interval [CI], −1.99 to −0.66 log10 copies/mL; P < .001). In addition, more patients in group A were polymerase chain reaction–negative at week 24 (39% vs 12%; odds ratio, 4.46 [95% CI, 1.86 – 10.72]; P = .001).
Compared with patients who received continuous adefovir (group B), mean residual HBV DNA at week 52 was lower in patients treated continuously with (group A) or who switched to (group C) telbivudine (3.01 log10 copies/mL [group A] and 3.02 log10 copies/mL [group C] vs 4.00 log10 copies/mL [group B]; difference, −0.99 log10 copies/mL [95% CI, −1.67 to −0.32 log10 copies/mL], and −0.98 log10 copies/mL [95% CI, −1.64 to −0.32 log10 copies/mL]; P = .004).
All 3 groups had similar adverse events; the most frequently reported were upper respiratory symptoms, headache, back pain, and diarrhea.
"Telbivudine demonstrated greater and more consistent HBV DNA suppression than adefovir after 24 weeks of treatment," the authors write. "After 52 weeks, HBV DNA suppression was greater in patients who had received continuous telbivudine or were switched to telbivudine after 24 weeks than in those who received continuous adefovir."
Study limitations included open-label design, insufficient size or duration to compare clinical outcomes and long-term efficacy, and limited generalizability because the patients were all HBeAg-positive and nucleoside- and nucleotide-naive and were primarily Asian.
"Data from this study support the concept that maximizing viral suppression early in the course of therapy is linked to improved efficacy responses and less resistance, suggesting that agents providing the greatest viral suppression may be preferable as initial therapy," the authors conclude. "Data from this and previous studies indicate that telbivudine may provide greater viral suppression than adefovir and lamivudine. With regular monitoring to ensure that responses are maintained, telbivudine may have an important role in treatment regimens for patients with chronic hepatitis B."
Some of the authors report potential financial conflicts of interest, including employment in some cases, with Novartis, Idenix Pharmaceuticals, Bristol-Myers Squibb, Canadian Health Protection Board, Roche, Vertex, Schering-Plough, GlaxoSmithKline, Bristol-Myers Squibb, Gilead Sciences, Wyeth, Human Genome Sciences, and/or Celera.
Ann Intern Med. Published online October 1, 2007.