}

Peginterferon Alfa-2b

Antivirals

Drug Overview

Peginterferon alfa-2b (brand name PegIntron) is a pegylated form of interferon used to boost the body’s natural antiviral defenses. By attaching a polyethylene glycol (PEG) molecule, the drug remains in circulation longer, allowing for once-weekly dosing.

This medication is primarily indicated, in combination with ribavirin, for the treatment of chronic hepatitis C infection. It may also be used off-label for other viral illnesses under specialist supervision.

Peginterferon alfa-2b binds to interferon receptors on host cells, activating the JAK-STAT signaling pathway and upregulating dozens of antiviral genes. The net result is reduced viral replication and improved immune-mediated clearance of infected cells.

Relevant Genes and Their Roles

The primary gene influencing response to peginterferon alfa-2b is IFNL3 (formerly IL28B). IFNL3 encodes interleukin-28B, a cytokine that modulates the antiviral immune response by enhancing natural killer cell activity and promoting the expression of interferon-stimulated genes.

Variants in the promoter region of IFNL3 affect how strongly these antiviral pathways are activated when interferon therapy is given. Simply put, some genotypes lead to a more robust immune response, while others result in weaker interferon signaling and lower treatment success rates.

Impact of Genetics on Drug Response

Individuals with a favorable IFNL3 genotype experience stronger interferon-driven antiviral activity, higher rates of sustained virologic response (SVR), and may be eligible for shorter treatment courses. Those with an unfavorable genotype exhibit reduced viral clearance, lower SVR rates, and may require alternative therapies or full-length treatment courses.

Expected Clinical Effects of Genetic Variation

Favorable response genotype

  • Effect: Enhanced interferon signaling leading to improved viral clearance
  • Clinical consequence: Approximately 70% chance of sustained virologic response after 48 weeks of treatment
  • Side effects: Flu-like symptoms (fever, fatigue, muscle aches); moderate severity; common

Unfavorable response genotype

  • Effect: Reduced interferon activity and slower viral clearance
  • Clinical consequence: Approximately 30% chance of sustained virologic response after 48 weeks
  • Side effects: Flu-like symptoms (fever, fatigue); moderate severity; common

Indeterminate/Not Available

  • Effect: Unknown
  • Clinical consequence: No specific guidance; follow standard dosing with clinical monitoring

Dosing Guidelines

The following dosing guidelines are based on the available guidelines for peginterferon alfa-2b and IFNL3 genotype.

IFNL3 Dosing Guideline

Phenotype Clinical Consequence Guideline Recommendation
Favorable response genotype Approximately 70% chance for sustained virologic response after 48 weeks of treatment. Consider implications before initiating PEG-IFN alpha and RBV regimens. Approximately 90% chance for SVR after 24–48 weeks of treatment. 80–90% eligible for shortened therapy (24–28 weeks vs. 48 weeks). Consider interferon-based regimen.
Unfavorable response genotype Approximately 30% chance for sustained virologic response after 48 weeks of treatment. Consider implications before initiating PEG-IFN alpha and RBV regimens. Approximately 60% chance for SVR after 24–48 weeks of treatment. 50% eligible for shortened therapy (24–28 weeks). Consider alternative regimens.
Indeterminate / Not available Unknown impact Initiate standard starting dose

Alternative Treatment Options

Examples of alternative approaches from guidelines include interferon-free, direct-acting antiviral regimens such as sofosbuvir-ledipasvir or other NS5B/NS5A inhibitors. These options may be preferred for patients with unfavorable IFNL3 genotypes, under physician guidance.

Sources and References

Disclaimer: This document is for informational purposes only and is not a substitute for medical advice. Clinical decisions should be made by a qualified healthcare professional.

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