Induction dosing of peginterferon alfa-2a (40 KD) and/or high-dose ribavirin in genotype 1 CHC patients with difficult-to-treat characteristics: pharmacokinetic and viral kinetic (PK/VK) assessment from PROGRESS.
OBJECTIVE
PROGRESS randomized chronic hepatitis C genotype 1 patients with a baseline viral load ≥400,000 IU/mL weighing ≥85 kg to regimens of 180 μg/week for 48 weeks or 360 μg/week for 12 weeks followed by 180 μg/week for 36 weeks peginterferon alfa-2a plus ribavirin. This analysis explored pharmacokinetics and early viral kinetics (VK) and evaluates differences between groups.


METHODS
Blood samples for pharmacokinetic and VK analyses were collected from 51 patients enrolled in the PROGRESS study.


RESULTS
Mean peginterferon alfa-2a trough concentration at week 12 was 11.7±4.3 ng/mL for 180 μg and 23.4±11.3 ng/mL for 360 μg. Early VK profiles suggested a trend towards an enhanced viral decline in the 360 μg groups with a mean decrease in HCV RNA at 48 hours post first dose of 1.04 log10 (IU/mL) compared with 0.76 log10 (IU/mL) in the 180 μg groups. Mean beta slope increased with dose, ranging from 0.38±0.26 log10 IU/week at 180 μg to 0.52±0.32 log10 IU/week at 360 μg.


CONCLUSIONS
Early viral de clines may be enhanced with the 360 μg dose. These data may suggest the utility of high-dose peginterfer on alfa-2a plus direct-acting antivirals (DAA) in select difficult-to-treat populations.
Peter N
PN
Morcos
Ruby
R
Leong
James A
JA
Thommes
Jean
J
DePamphilis
Joseph F
JF
Grippo
Barbara J
BJ
Brennan
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D015415:Biomarkers / Q000097:blood; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D012254:Ribavirin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D016896:Treatment Outcome; D014481:United States; D019562:Viral Load
D000998:Antiviral Agents; D015415:Biomarkers; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a