Low‐ and standard‐dose peginterferon alfa‐2a for chronic hepatitis C, genotype 2 or 3: efficacy, tolerability, viral kinetics and cytokine response

• Published in: Alimentary pharmacology & therapeutics 2010-05, Vol.31 (9), p.1018-1027
• Main Authors: ROTMAN, Y., BORG, B. B., SOZA, A., FELD, J. J., MODI, A. A., LOOMBA, R., LUTCHMAN, G., RIVERA, E., DOO, E., GHANY, M. G., HELLER, T., NEUMANN, A. U., LIANG, T. J., HOOFNAGLE, J. H.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antiviral Agents - therapeutic use; Biological and medical sciences; Chronic infection; Cytokines; Cytokines - metabolism; Digestive system; Dose-Response Relationship, Drug; Drug Therapy, Combination; Fatigue; Female; Gastroenterology. Liver. Pancreas. Abdomen; Genotype; Genotypes; Hepatitis C; Hepatitis C, Chronic - drug therapy; Human viral diseases; Humans; Infectious diseases; Interferon-alpha - administration & dosage; IP-10 protein; Kinetics; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Polyethylene Glycols - administration & dosage; Recombinant Proteins; Ribavirin; Ribavirin - administration & dosage; RNA, Messenger - metabolism; Toxicity; Treatment Outcome; Viral diseases; Viral hepatitis
• ISSN: 0269-2813; 1365-2036
• DOI: 10.1111/j.1365-2036.2010.04263.x

Aliment Pharmacol Ther 31, 1018–1027 Summary Background  Chronic infection with hepatitis C, genotype 2/3, responds better than other genotypes to peginterferon and ribavirin treatment. We hypothesized that a lower dose of peginterferon would be as effective, but less toxic than standard doses. Aim  To test the hypothesis that a lower dose of peginterferon would be as effective as, but less toxic than, standard doses. Methods  A total of 30 patients were treated with low‐dose peginterferon alfa‐2a (90 μg/week) and 27 patients with standard doses (180 μg/week) for 24 weeks in combination with 800 mg/day of ribavirin. Patients who failed treatment were offered 48 weeks of standard‐dose treatment. Viral and serum inducible protein 10 (IP‐10) levels were measured and early viral kinetic parameters were calculated. Results  Sustained virological response was achieved in 68% of the low‐dose and 87% of the standard‐dose patients (per protocol, P = 0.79 for non‐inferiority). Re‐treatment was successful in all patients who tolerated full dose and duration. The standard‐dose group had greater first‐phase declines of viral levels and faster time to negativity. The second‐phase slope was not dose‐dependent. IP‐10 induction was significantly greater with the standard dose. Although fatigue and general feeling during treatment were worse for standard dose, haematological toxicity and depression did not differ between groups. Conclusion  A lower dose of peginterferon is associated with some symptomatic benefit, but the response is not equivalent to standard dosing.