|
- 现金
- 62111 元
- 精华
- 26
- 帖子
- 30437
- 注册时间
- 2009-10-5
- 最后登录
- 2022-12-28
|
Oops: Data Supporting Tenofovir Over Entecavir for Hepatitis B Retracted
Still superior for preventing liver cancer, but mortality/transplant advantage disappears
by Molly Walker, Staff Writer, MedPage Today
April 25, 2019
Maybe tenofovir diproxil fumarate (TDF, Viread) isn't better than entecavir (Baraclude) for keeping hepatitis B alive and transplant-free after all.
Data from a Korean study published online last September, indicating reduced risk for mortality or transplant with TDF versus entecavir, have been retracted and replaced, according to a letter in the April 25 issue of JAMA Oncology from two of the original paper's authors.
Citing "inadvertent errors" in determining follow-up duration for participants, the researchers recalculated the hazard ratio for mortality or transplant and found that it no longer significantly favored TDF (HR 0.89, 95% CI 0.73-1.07), according to Young-Suk Lim, MD, PhD, and Min Jung Ko, PhD, both of the University of Ulsan College of Medicine in Seoul.
"We sincerely apologize for these unintentional errors, and considering the extent of the corrections, we have requested that the original article be retracted and replaced," Lim and Ko wrote.
Their study gained prominence after being cited earlier this month at the European Association for the Study of the Liver (EASL) annual meeting. A study in a cohort out of Hong Kong -- with similar large numbers of patients on entecavir therapy and smaller numbers of patients on tenofovir -- was presented as a late-breaker abstract that indicated TDF was superior for preventing development of hepatocellular carcinoma.
At an EASL press conference, moderator Francesco Negro, MD, of the University Hospital of Geneva in Switzerland, urged caution with those results, with additional researchers saying there may be other factors that were not included in the Hong Kong study's propensity score analysis.
A January editorial in JAMA Oncology accompanying the Korean study's print publication, by Jennifer A. Flemming, MD, of Queen's University in Kingston, Ontario, and Norah A. Terrault, MD, of the University of California San Francisco, also backed a wait-and-see approach.
"We would advocate for additional observational cohorts with data on liver disease severity, virologic response, and adherence to surveillance to evaluate this important question," the editorialists wrote. "This study should not lead to a widespread paradigm shift in selecting TDF over [entecavir]."
The April 25 JAMA Oncology also carried three letters of comment on the Korean study, although Lim and Ko only referred to one from Yuanyuan Kong, PhD, of Beijing Friendship Hospital in China, which cited "inconsistent data presentations."
Lim and Ko said that following this letter, they conduced an "extensive and thorough review" of the data. In addition to the corrected hazard ratio for mortality and transplant in the TDF group, they included the following corrections:
Number of reported mortality or transplant cases changed from 281 to 269 in the entecavir group, and from 228 to 190 in the tenofovir treatment group
Hazard ratios for hepatocellular carcinoma in the full TDF cohort changed from 0.61 (95% CI 0.54-0.70) to 0.68 (95% CI 0.59-0.77) relative to entecavir, which remained statistically significant
Douglas Dieterich, MD, of the Icahn School of Medicine at Mount Sinai in New York City, who was not involved in the research, said that "the data is going in both directions" when looking at TDF versus entecavir in this population.
He also noted "all sorts of confounders" in this type of analysis, including time on the drug and potential entecavir resistance.
"There's a signal, it's just not clear which way the signal is pointing. We need somebody to combine all these studies together and do a super meta-analysis looking at all the factors," Dieterich told MedPage Today.
He included the caveat that his team at Mount Sinai is also looking at a similar type of analysis of tenofovir in a multi-ethnic cohort of patients with chronic hepatitis B infection. Their early data suggests tenofovir may be better at treating HBV, he said.
"We're not saying [our study] can settle it, but there's clearly something going on. We'll need to wait until we have enough data to make a decision about how to evaluate [TDF vs entecavir] in different sample sizes," Dieterich said.
Lim disclosed support from Gilead Sciences and Bayer Healthcare.
Ko disclosed no conflicts of interest.
Primary Source
JAMA Oncology
Source Reference: Lim Y-S, Ko MJ "Notice of Retraction and Replacement. Choi et al. Risk of hepatocellular carcinoma in patients treated with entecavir vs tenofovir for chronic hepatitis B: a Korean nationwide cohort study. JAMA Oncol. 2019;5(1):30-36" JAMA Oncol 2019; DOI: 10.1001/jamaoncol.2019.0576.
|
|
发表于 2019-4-26 11:47
