Predictors of response to tenofovir disoproxil fumarate plus peginterferon alfa‐2a combination therapy for chronic hepatitis B

Marcellin, Patrick; Ahn, Sang Hoon; Chuang, Wan‐Long; Hui, Aric Josun; Tabak, Fehmı; Mehta, Rajiv; Petersen, J.; Lee, C.‐M.; Ma, Xiao; Căruntu, Florin Alexandru; Tak, Won Young; Elkhashab, Magdy; Lin, Lanjia; Wu, George Y.; Martins, Eduardo B.; Charuworn, Prista; Yee, Leland J.; Lim, Seng Gee; Foster, Graham R.; Fung, Scott; Morano, Luís; Samuel, Didier; Agarwal, Kosh; İdilman, Ramazan; Strasser, Simone I.; Buti, Marı́a; Gaeta, G. B.; Papatheodoridis, George V.; Flisiak, Robert; Chan, Henry Lik Yuen

doi:10.1111/apt.13779

Cited by 38 publications

(33 citation statements)

References 26 publications

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“…Theoretically, a combined NA and PegIFNa approach may provide advantages by combining the potent antiviral effect of NA plus the immune modulation of IFNa. 1,56,62,63 The evidence for superiority of such a combined approach, however, is lacking, and there are still many unresolved issues with respect to patient selection, timing, as well as the duration of the combination strategy, which may be addressed in future studies.…”

Section: 5657mentioning

confidence: 99%

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

Lampertico¹,

Agarwal²,

Berg³

et al. 2017

Journal of Hepatology

4,198

3,081

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Section: 5657mentioning

confidence: 99%

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

Lampertico¹,

Agarwal²,

Berg³

et al. 2017

Journal of Hepatology

4,198

3,081

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“…Similar trends have been described for individual studies in the literature. For example, a similar genotype effect (larger decline in HBsAg levels for genotype B vs C) has been observed, albeit for HBsAg declines at week 48, in HBeAg‐negative and ‐positive patients 31,32 . In addition, baseline HBsAg levels have been described as predictors for HBsAg loss in HBeAg‐negative patients 33 .…”

Section: Discussionmentioning

confidence: 68%

Systematic review with meta‐analysis: hepatitis B surface antigen decline and seroclearance in chronic hepatitis B patients on nucleos(t)ide analogues or pegylated interferon therapy

et al. 2020

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Background: Surface antigen (HBsAg) seroclearance in chronic hepatitis B (CHB)is associated with improved outcomes and permits safe treatment discontinuation. Current treatments (nucleos(t)ide analogues [NA], pegylated interferon [pegIFN])have low HBsAg seroclearance rates. New therapies aim to improve these rates.Aim: To use historical data to quantify the mean change from baseline in HBsAg at week 24 and the seroclearance rate at week 48 under standard-of-care treatment. Methods:We searched PubMed, ClinicalTrials.gov, and conference presentations for CHB studies with NAs (tenofovir, entecavir) or pegIFN. HBsAg decline and seroclearance were evaluated by a random effects meta-analysis. Treatment type, HBsAg baseline values, and hepatitis B virus (HBV) genotype, recruitment region were explored as heterogeneity sources. Results:One hundred and fifty-eight cohorts (over 10 000 patients; 71 studies [randomised controlled; prospective cohorts; retrospective cohorts]) were analysed. With NAs, 24-week HBsAg decline was minimal for treatment-naïve HBeAgnegative, and virologically suppressed patients. Considerable heterogeneity was observed in NA-treated HBeAg-positive patients, impacted by HBV genotype, NA type and HBsAg baseline levels. 48-week HBsAg seroclearance rates were low in all NA-treated groups (<1%/group). HBsAg declines and seroclearance rates were greater with pegIFN (also greater intra-subject variation within studies) vs NAs. Conclusions:This meta-analysis demonstrates good consistency between studies and limited within-study variation for the endpoint of HBsAg seroclearance at week 48 on NA treatment. For novel agents, these results can be applied to quantify control arm performance in study designs with historical borrowing. | 107 SLAETS ET AL.

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“…Regarding the efficacy of adding PEG-IFN to NA therapy, Ouzan et al reported that the addition of 180 μ g of PEG-IFN- α -2a for a maximum of 96 weeks based on HBsAg-titer monitoring led to a loss of HBsAg and cessation of NA therapy in six out of ten patients (60%), with no relapse [17]. Marcellin et al reported that the rates of HBs Ag loss were significantly higher in the group treated with tenofovir plus PEG-IFN for 48 weeks than in the group (6.5%) treated with tenofovir plus PEG-IFN for 16 weeks and tenofovir for 32 weeks (0.5%) [18]. Therefore, longer-term add-on PEG-IFN- α -2a therapy would be needed for the cessation of NA.…”

Section: Discussionmentioning

confidence: 99%

Add-on Pegylated Interferon Alpha-2a Therapy in Chronic Hepatitis B Japanese Patients Treated with Entecavir

Tamai

Ida

Shingaki

et al. 2017

Hepatitis Research and Treatment

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Entecavir requires long-term administration. Pegylated interferon (PEG-IFN) therapy leads to significant reduction of hepatitis B surface antigen (HBs Ag) levels. This study aimed to assess the safety and efficacy of adding PEG-IFN-α-2a to entecavir toward cessation of entecavir. A total of 23 patients treated with entecavir underwent add-on PEG-IFN-α-2a therapy (90 μg per week) for 48 weeks. Viral response (VR) was defined as more than 50% reduction of baseline hepatitis B surface antigen (HBs Ag) level at 72 weeks from the start of therapy. Complete response (CR) was defined as the decline of HBs Ag levels <100 IU/mL. Hepatitis B e antigen (HBe Ag) seroconversion rate was 25% (2/8), and VR rate was 52% (12/23). CR was observed in four patients (17%). However, CR rate in baseline HBs Ag level <2000 IU/mL and HBe Ag negative patients was 50% (4/8). Univariate analysis showed that the percentage of HBs Ag level reduction at week 12 was significantly associated with VR. The area under the curve value was 0.848. Adding PEG-IFN-α-2a to entecavir has limited efficacy. The percentage reduction of HBs Ag level at week 12 may be a useful predictor for VR.

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Predictors of response to tenofovir disoproxil fumarate plus peginterferon alfa‐2a combination therapy for chronic hepatitis B

Abstract: SUMMARY BackgroundIn patients with chronic hepatitis B, tenofovir disoproxil fumarate (TDF) plus pegylated interferon (PEG-IFN) for 48-weeks results in higher rates of hepatitis B surface antigen (HBsAg) loss than either monotherapy.

Cited by 38 publications

References 26 publications

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

Systematic review with meta‐analysis: hepatitis B surface antigen decline and seroclearance in chronic hepatitis B patients on nucleos(t)ide analogues or pegylated interferon therapy

Add-on Pegylated Interferon Alpha-2a Therapy in Chronic Hepatitis B Japanese Patients Treated with Entecavir

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