Biological and clinical significance of neutralizing and binding antibodies to interferon-alpha (IFN–α) during therapy for chronic hepatitis C

Giannelli, Gianluigi; Antonelli, Guido; Fera, G; Vecchio, S. Del; Riva, Elisabetta; Broccia, C.; Schiraldi, O; Dianzani, F.

doi:10.1111/j.1365-2249.1994.tb06571.x

Cited by 53 publications

(16 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…demonstrated that Ab production is low and not hampering treatment responses to PEG‐IFN. Furthermore, these results are also supported by earlier studies showing no significant differences in overall percentage of sero‐conversion between responders and non‐responders. The differences in AST but not ALT levels found here are also in agreement with a recent report showing that rapid normalization of ALT by 4 weeks after treatment might be an independent significant predictive factor for SVR.…”

Section: Discussionsupporting

confidence: 87%

A comparative study of variants of pegylated interferon alpha in treatment of chronic HCV patients

Sabaawy

El-Haggar

El-Bahrawy

et al. 2015

APMIS

View full text Add to dashboard Cite

HCV infection presents a vast burden in the regions of high prevalence such as Egypt, where most HCV isolates are genotype 4b. Combined treatment of three variants of pegylated interferon and ribavirin is still the standard of care in Egypt. However, no conclusive data confirming their efficacy are available. Here, 60 chronic HCV patients were randomized for ribavirin plus Peg Intron (PEG-IFNα-2b), Pegasys (PEG-IFNα-2a) or Reiveron Retard (PEG-IFNα-2a). Serum interferon and antibody (Ab) levels were measured, and responses and costs were compared. Serum interferon levels were higher in Pegasys group (1625.1 ng/mL) followed by Reiveron Retard (1076.5 ng/mL), and Peg Intron group (857.72 ng/mL). Moreover, Ab levels were the lowest in Reiveron Retard group (318.4 ng/mL), followed by Peg Intron (439.93 ng/mL), and Pegasys cases (610.83 ng/mL). The best 24-week response rates were detected in the Pegasys group (73.3%), followed by Peg Intron (66.67%), and Reiveron Retard (40%). Treatment with both Pegasys and Peg Intron were most cost-effective. Furthermore, Pegasys was superior in both 6-month response and serum interferon, despite having higher Ab levels (more antigenicity). Our data have notable clinical implications and suggest that Pegasys may be a superior choice of interferon therapy for chronic HCV under low socioeconomic conditions.

show abstract

Section: Discussionsupporting

confidence: 87%

A comparative study of variants of pegylated interferon alpha in treatment of chronic HCV patients

Sabaawy

El-Haggar

El-Bahrawy

et al. 2015

APMIS

View full text Add to dashboard Cite

show abstract

“…Anti-IFN NAbs were reported to be associated with a poor response of CH-C treated with IFN, particularly in patients treated with non-natural recombinant IFNs [29][30][31][32] . With regard to HCV-infected patients receiving rIFN-α, several previous studies have suggested that anti-IFN-α NAb were more frequently detected in the sera of non-responders than in that of responders [29][30][31][32] . Because of the difficulty in obtaining a SVR, Japanese HCV-infected patients with "1b/high" sometimes received multiple kinds of IFN therapy, and frequently develop anti-IFN-α NAbs.…”

Section: The Role Of Anti-ifn-α Neutralizing Antibodies In Ifn-α Treamentioning

confidence: 99%

Factors associated with the response to interferon-based antiviral therapies for chronic hepatitis C

Enomoto

Nishiguchi

2015

WJH

View full text Add to dashboard Cite

Hepatitis C virus (HCV) infection is a major health concern worldwide. Interferon-α (IFN-α) therapy has been the main antiviral treatment for more than 20 years. Because of its established antitumor effects, IFNbased treatments for chronic HCV infection still have a clinical impact, particularly for patients with high risk conditions of developing hepatocellular carcinoma, such as older age and advanced liver fibrosis. As a result of exhaustive research, several viral factors, including NS5A amino acid mutations such as the IFN sensitivitydetermining region and the IFN/ribavirin resistancedetermining region, and mutations of amino acids in the core protein region (core 70 and 91) were shown to be associated with the response to IFN-α treatment. In addition, among the host factors related to the response to IFN-α treatment, polymorphisms of the interleukin-28B gene were identified to be the most important factor. In this article, we review the factors associated with the efficacy of IFN-α treatment for chronic HCV infection. In addition, our recent findings regarding the possible involvement of anti-IFN-α neutralizing antibodies in a non-response to pegylated-IFN-α treatment are also described. Core tip: Interferon-α (IFN-α) therapy has been playing a central role in anti-hepatitis C virus (HCV) strategies, and several viral and host factors related to the treatment efficacy have been identified. After the development of pegylated-IFN-α (Peg-IFN-α), the clinical impact of anti-IFN-α neutralizing antibodies in the treatment for HCV infection has not been sufficiently addressed. We recently found that anti-IFN-α neutralizing antibodies were associated with a non-response to Peg-IFN-α treatment. Our findings provide important information for the treatment of chronic hepatitis C in the clinical setting. MINIREVIEWSSubmit a

show abstract

“…Antibody formation due to the immunogenicity of recombinant human proteins in animal studies (Toon 1996) and against human recombinant IFNs used for a variety of indications (Antonelli & Dianzani 1999; Bertolotto et al 2004), including the use of recombinant human IFN‐α during the treatment of hepatitis C virus infection (Milella et al 1993 & 1995; Giannelli et al 1994; Antonelli 1995 & 1996; Haria & Benfield 1995; Bonino et al 1997; Hoffman et al . 1999) is well known, so our observations were not unexpected.…”

Section: Discussionmentioning

confidence: 99%

Safety Pharmacology, Toxicology and Pharmacokinetic Assessment of Recombinant Human ω‐Interferon Produced from CHO‐SS Cells

Buckwold¹,

Lang

Scribner

et al. 2006

Basic Clin Pharma Tox

View full text Add to dashboard Cite

Human w-interferon (IFN-w) has been shown to be well-tolerated in man and to induce reductions of hepatitis C virus RNA levels in a series of human clinical trials. Here we provide an overview of our preclinical safety evaluation of the fully-glycosylated human IFN-w produced from CHO-SS cells that is currently being evaluated clinically. IFN-w was not associated with any biologically-relevant adverse effects in a series of 10 safety pharmacology experiments, in the Ames mutagenicity test, in the micronucleus test, or in intraarterial, intravenous, paravenous or subcutaneous local tolerance studies. Acute, subacute, subchronic and reproductive toxicity studies performed in cynomolgus monkeys and rats showed a toxicity profile similar to that of human a interferon (IFN-a). Except for the acute (single-dose) toxicology study, all of the other toxicity studies showed evidence for the formation of anti-IFN-w antibodies over time in the animals. These antibodies were found to neutralize IFN-w antiviral activity in vitro in a dose-dependent manner. The average pharmacokinetic parameters following a single subcutaneous dose of IFN-w in rabbits, rats and monkeys were determined and found to be similar to that of human IFN-a. These findings demonstrate that IFN-w has a safety profile consistent with that required for its use in man. IFN-w might be beneficial for the treatment of patients infected with hepatitis C virus who fail to respond to IFN-a or as a first-line treatment option.

show abstract

Biological and clinical significance of neutralizing and binding antibodies to interferon-alpha (IFN–α) during therapy for chronic hepatitis C

Cited by 53 publications

References 21 publications

A comparative study of variants of pegylated interferon alpha in treatment of chronic HCV patients

A comparative study of variants of pegylated interferon alpha in treatment of chronic HCV patients

Factors associated with the response to interferon-based antiviral therapies for chronic hepatitis C

Safety Pharmacology, Toxicology and Pharmacokinetic Assessment of Recombinant Human ω‐Interferon Produced from CHO‐SS Cells

Contact Info

Product

Resources

About