- 现金
- 62111 元
- 精华
- 26
- 帖子
- 30437
- 注册时间
- 2009-10-5
- 最后登录
- 2022-12-28
|
CT-4251
Clinical Trials in Progess
A RANDOMISED PROSPECTIVE OPEN-LABEL TRIAL COMPARING PEGINTERFERON + ADEFOVIR AND
PEGINTERFERON + TENOFOVIR VERSUS NO TREATMENT IN HBEAG NEGATIVE CHRONIC HEPATITIS B
PATIENTS WITH LOW VIRAL LOAD: INTERIM ANALYSIS OF WEEK 48 RESULTS
Annikki de Niet* 1, Louis Jansen1, Femke Stelma1, Sophie B. Willemse1, Sjoerd D. Kuiken2, Sebastiaan Weijer3, Karin M.
van Nieuwkerk4, Hans L. Zaaijer5, 6, Richard Molenkamp5, Robert B. Takkenberg1, Maarten Koot7, Joanne Verheij8, Ulrich
Beuers1, Hendrik W. Reesink1
1Gastroenterology and Hepatology, Academic Medical Centre, 2Gastroenterology and Hepatology, Sint Lucas Andreas
Hospital, Amsterdam, 3Internal Medicine, Medical Centre Zuiderzee, Lelystad, 4Gastroenterology and Hepatology, VU
Medical Centre, 5Medical Microbiology, Academic Medical Centre, 6Blood-borne Infections, 7Virus Diagnostic Services,
Sanquin, 8Pathology, Academic Medical Centre, Amsterdam, Netherlands
Corresponding author’s email: [email protected]
Do you want to apply for a Young Investigator Bursary?: No
Background and Aims: Chronic hepatitis B (CHB) patients with a low viral load (LVL) are currently not eligible for antiviral
treatment. However, they comprise the largest group of hepatitis B virus-infected patients and are still at risk to develop
cirrhosis or hepatocellular carcinoma. Here we present the week 48 results of a randomized trial comparing combination
treatment of peginterferon alfa-2a (Peg-IFN) and a nucleotide analogue versus no treatment for CHB patients with LVL.
Methods: 134 CHB patients (HBeAg-negative, HBV-DNA <20,000 IU/mL) were randomized 1:1:1 to receive Peg-
IFN+adefovir (arm I; n=46), Peg-IFN+tenofovir (arm II; n=45) or no treatment (arm III; n=43) for 48 weeks (ITT
population). Randomization was stratified by HBV genotype A (22%), non-A (B 7%, C 4%, D 26%, E/F/G 20%), or
indeterminate (21%). The median age was 43 years, 57% were male. Twelve patients discontinued the study before
week 48 (5 in arm I, 6 in arm II, 1 in arm III). HBsAg loss (AxSYM <0.05 IU/mL) and quantitative HBsAg level (Architect)
was determined at regular intervals, and were compared using Fisher’s, Mann-Whitney U or Wilcoxon test.
Results: At week 48, 4 patients receiving combination therapy had achieved HBsAg loss, compared to none of the
untreated patients (ITT 4.4% vs 0.0%, p=0.31). Patients with HBsAg loss were treated in arm I (n=1) and arm II (n=3),
and had HBV genotype A (n=1), B (n=1), or indeterminate (n=2). Baseline HBsAg levels were comparable between study
arms (median 3.34 log IU/mL ). In a per-protocol analysis, HBsAg level had declined significantly in all arms at week 48; -
0.33 (p<0.001), -0.22 (p<0.001), and -0.07 (p=0.02) median log reduction for arms I, II, and III, respectively. No difference
in HBsAg decline was observed between treatment arms. However, HBsAg declined more in treatment arms I (p<0.001)
and II (p=0.002) compared to the control arm III. A strong HBsAg decline of >1.0 log IU/mL was observed in 17 treated
patients (21%), but in none of the untreated patients (p<0.001). No unexpected adverse events were observed in the
treatment arms.
Conclusions: In CHB patients with a low viral load, 48 weeks of combination treatment with Peg-IFN and adefovir or
tenofovir resulted in 4.4% HBsAg loss, compared to 0.0% in the untreated control group. The significant decline in HBsAg
at week 48 may indicate a further increase in the rate of HBsAg loss during treatment-free follow-up. Week 72 results are
expected in March 2015.
Disclosure of Interest: A. de Niet: : None Declared, L. Jansen: : None Declared, F. Stelma: : None Declared, S.
Willemse: Sponsored Lectures (National or International): Gilead, Roche, BMS en Janssen, S. Kuiken: : None Declared,
S. Weijer: : None Declared, K. van Nieuwkerk: : None Declared, H. Zaaijer: : None Declared, R. Molenkamp: : None
Declared, R. Takkenberg: Consultant: Bristol Myers Squibb and Gilead Sciences, M. Koot: : None Declared, J. Verheij: :
None Declared, U. Beuers: : None Declared, H. Reesink: Grant: Bristol Myers Squibb, Gilead Sciences, Roche, Merck,
Replicor and Alnylam, Consultant: Bristol Myers Squibb, Gilead Sciences, Roche, Merck, Korean Green Cross, Replicor
and Alnylam
|
|