Novel Pegylated Interferon for the Treatment of Chronic Viral Hepatitis

Huang, Yi‐Wen; Qin, Albert; Tsai, Chan‐Yen; Chen, Pei‐Jer

doi:10.3390/v14061128

Cited by 14 publications

(12 citation statements)

References 88 publications

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“…It has anti-HBV and immunomodulatory effects, and plays a variety of key roles in innate and adaptive immune responses ( 52 ). Many studies have proved that the therapeutic effect of PegIFNα for its induction of the repression of specific interferon-stimulated genes (ISGs) and secretion of antiviral proteins ( 53 , 54 ).…”

Section: Anti-viral Therapy and Host Immune Responsementioning

confidence: 99%

Hepatitis B functional cure and immune response

2022

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Hepatitis B virus (HBV) is a hepatotropic virus, which damage to hepatocytes is not direct, but through the immune system. HBV specific CD4+ T cells can induce HBV specific B cells and CD8+ T cells. HBV specific B cells produce antibodies to control HBV infection, while HBV specific CD8+ T cells destroy infected hepatocytes. One of the reasons for the chronicity of HBV infection is that it cannot effectively activate adoptive immunity and the function of virus specific immune cells is exhausted. Among them, virus antigens (including HBV surface antigen, e antigen, core antigen, etc.) can inhibit the function of immune cells and induce immune tolerance. Long term nucleos(t)ide analogues (NAs) treatment and inactive HBsAg carriers with low HBsAg level may “wake up” immune cells with abnormal function due to the decrease of viral antigen level in blood and liver, and the specific immune function of HBV will recover to a certain extent, thus becoming the “dominant population” for functional cure. In turn, the functional cure will further promote the recovery of HBV specific immune function, which is also the theoretical basis for complete cure of hepatitis B. In the future, the complete cure of chronic HBV infection must be the combination of three drugs: inhibiting virus replication, reducing surface antigen levels and specific immune regulation, among which specific immunotherapy is indispensable. Here we review the relationship, mechanism and clinical significance between the cure of hepatitis B and immune system.

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Section: Anti-viral Therapy and Host Immune Responsementioning

confidence: 99%

Hepatitis B functional cure and immune response

2022

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“…In addition, side effects, including flu-like symptoms, injection site reactions and psychiatric disorders such as depression, have the ability to limit their long-term use. 21 The frequent dosing schedule could make patients less compliant with medications.…”

Section: Introductionmentioning

confidence: 99%

“…IFN‐α therapies have often been associated with a short half‐life, requiring frequent injections ranging from three times each week to once every week. In addition, side effects, including flu‐like symptoms, injection site reactions and psychiatric disorders such as depression, have the ability to limit their long‐term use 21 . The frequent dosing schedule could make patients less compliant with medications.…”

Section: Introductionmentioning

confidence: 99%

Exposure–efficacy and exposure–safety analyses of ropeginterferon alfa‐2b treatment in patients with polycythaemia vera

Qin,

Wu,

et al. 2024

Brit J Clinical Pharma

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AimsTo investigate the exposure–response (E‐R) relationship, including exposure–efficacy and exposure–safety, of ropeginterferon alfa‐2b treatment in patients with polycythaemia vera (PV).MethodsBased on the results of the phase II trial A20‐202 regarding ropeginterferon alfa‐2b in patients with PV, E‐R analyses were performed to evaluate the efficacy and safety of the given dosing regimen. The E‐R analyses were based on logistic and linear regression and the relationship between exposure to ropeginterferon alfa‐2b and key efficacy and safety variables. The key efficacy variables included complete haematologic response (CHR) and reduction of the driver mutation JAK2V617F. The safety variable was treatment‐related adverse events (TRAEs).ResultsA clear relationship between the exposure to ropeginterferon alfa‐2b and CHR was observed, with an increase in drug exposure resulting in an increased probability of achieving CHR. Similar CHR probabilities were observed in the third and fourth quantiles of the average concentration at Week 24. The results from the exposure–JAK2V617F model indicated that the JAK2V617F allele burden decreased with increasing exposure to ropeginterferon alfa‐2b and baseline body surface area. Exposure–safety analysis revealed a risk of AEs associated with transaminase abnormalities, which were not associated with clinical significance.ConclusionsOur analyses have shown that patients with PV treated with ropeginterferon alfa‐2b had an increased probability of achieving CHR and a molecular response with acceptable safety risks at the 250–350–500 μg titration dosing regimen. This study has provided the relevant data for the application of a biologics licence of ropeginterferon alfa‐2b for PV treatment in China.

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“…It can be injected less frequently, for example, once every two weeks [ 16 , 17 , 18 ]. It has been approved for the treatment of polycythemia vera (PV), a myeloproliferative neoplasm (MPN), in the United States and Europe [ 19 , 20 ] and is currently under development for more approvals [ 21 , 22 , 23 , 24 , 25 ]. In its Phase II clinical trial, the application of 450 μg of ropeginterferon alfa-2b every two weeks demonstrated good tolerability and manifested anti-hepatitis B virus (HBV) effects [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

Sequential Therapy with Ropeginterferon Alfa-2b and Anti-Programmed Cell Death 1 Antibody for Inhibiting the Recurrence of Hepatitis B-Related Hepatocellular Carcinoma: From Animal Modeling to Phase I Clinical Results

Qin,

Wu,

et al. 2023

IJMS

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Hepatocellular carcinoma (HCC) usually recurs after curative surgical resection. Currently, no approved adjuvant therapy has been shown to reduce HCC recurrence rates. In this study, the in vivo effect of sequential combination treatment with recombinant mouse interferon-alpha (rmIFN-α) and an anti-mouse-PD1 antibody on hepatitis B virus (HBV) clearance in mice was evaluated. A Phase I clinical trial was then conducted to assess the safety, tolerability, and inhibitory activity of sequential therapy with ropeginterferon alfa-2b and nivolumab in patients with HCC recurrence who underwent curative surgery for HBV-related HCC. The animal modeling study showed that HBV suppression was significantly greater with the rmIFN-α and anti-PD1 sequential combination treatment in comparison with sole treatment with rmIFN-α or anti-PD1. In the Phase I study, eleven patients completed the sequential therapy with ropeginterferon alfa-2b every two weeks for six doses at 450 µg, followed by three doses of nivolumab every two weeks up to 0.75 mg/kg. A notable decrease in or clearance of HBV surface antigen was observed in two patients. The dose-limiting toxicity of grade 3 alanine transaminase and aspartate aminotransferase increases was observed in one patient. The maximum tolerated dose was then determined. To date, no HCC recurrence has been observed. The treatment modality was well tolerated. These data support the further clinical development of sequential combination therapy as a post-surgery prophylactic measure against the recurrence of HBV-related HCC.

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Novel Pegylated Interferon for the Treatment of Chronic Viral Hepatitis

Cited by 14 publications

References 88 publications

Hepatitis B functional cure and immune response

Hepatitis B functional cure and immune response

Exposure–efficacy and exposure–safety analyses of ropeginterferon alfa‐2b treatment in patients with polycythaemia vera

Sequential Therapy with Ropeginterferon Alfa-2b and Anti-Programmed Cell Death 1 Antibody for Inhibiting the Recurrence of Hepatitis B-Related Hepatocellular Carcinoma: From Animal Modeling to Phase I Clinical Results

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