Positive and negative prediction of sustained virologic response at weeks 2 and 4 of treatment with albinterferon alfa-2b or peginterferon alfa-2a in treatment-naïve patients with genotype 1, chronic hepatitis C.
OBJECTIVE
Albinterferon alfa-2b is a novel, long-acting, fusion polypeptide that is dosed q2wk or q4wk. The predictive value of early virologic response during albinterferon alfa-2b or peginterferon alfa-2a treatment was investigated in interferon-naïve patients with genotype 1, chronic hepatitis C.


METHODS
Four hundred and fifty-eight patients were randomized to: albinterferon 900 or 1200 microg q2wk, or 1200 microg q4wk, or peginterferon 180 microg qwk. HCV RNA was measured by real-time PCR. A linear exhaustive search algorithm was used to determine the best SVR prediction algorithm in the per-protocol population (n=368), with inclusion of key ITT analyses to assess impact.


RESULTS
SVR rate: 54-67% (P=NS between arms). Rapid initial virologic response rate at week 2 (RIVR; viral decline >2 log(10)IU/mL) was 32-50% and gave rise to positive predictive value of 88-97% for SVR. No initial virologic response at week 4 (NIVR; viral decline <2 log(10)IU/mL; viral load >5.5 log(10)IU/mL) demonstrated a 100% negative predictive value for SVR. A sequential prediction algorithm based on viral kinetics at weeks 2 and 4 identified four prediction groups that reliably predicted SVR, positively or negatively, in 65-72% of patients.


CONCLUSIONS
Improved SVR prediction was obtained by integrating absolute levels and reduction of HCV RNA at treatment week 2 and 4. Patients with RIVR had a high likelihood of achieving SVR.
Neumann
Avidan U
AU
Bar-Ilan University, Goodman Faculty of Life Sciences, Bldg. 212, Rm. 210, 52900 Ramat-Gan, Israel. neumann@mail.biu.ac.il
Pianko
Stephen
S
Zeuzem
Stefan
S
Yoshida
Eric M
EM
Benhamou
Yves
Y
Mishan
Moshe
M
McHutchison
John G
JG
Pulkstenis
Erik
E
Mani Subramanian
G
G
D000328:Adult; D000418:Albumins / Q000627:therapeutic use*; D000465:Algorithms; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins
D000418:Albumins; D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C531108:albinterferon alfa-2b; C100416:peginterferon alfa-2a