INTERFERON ALFACON-1 INDUCTION THERAPY: A MULTICENTER TRIAL IN SUBJECTS WITH CHRONIC HEPATITIS C VIRUS INFECTION
     Rajender K Reddy, Univ of Miami, Miami, FL; Thomas Layden, Univ of Illinois at Chicago, Chicago, IL; F Blaine Hollinger, Baylor Coll of Medicine, Houston, TX; William Lee, The Univ of Texas, Dallas, TX; Robert W Reindollar, Carolina Ctr for Liver Diseases, Charlotte, NC; Myron Tong, Huntington Memorial Hosp, Pasadena, CA; Robert L Carithers, Univ of Washington, Seattle, WA; Teresa Wright, Acad Admin Medical Ctr, San Francisco, CA; Bernard Willems, St Luc Hosp, Montreal Canada; Paul J Pockros, Scripps Clin, La Jolla, CA

Sustained viral response following interferon monotherapy has ranged from 10 - 20%.

In an effort to improve response rates, we conducted a multicenter, randomized, controlled trial in 178 interferon-nave subjects with chronic HCV infection to examine the efficacy of 5 Interferon alfacon-1 induction regimens.

Subjects were stratified by baseline serum HCV RNA levels (2 strata: <106 copies/mL and > 106 copies/mL) and randomized in equal allocation to one of five 4-week induction regimens:

(1) 15 mg QD;
(2) 7.5 mg BID;
(3) 15 mg TIW;
(4) 9 mg QD; and
(5) 9 mg TIW.

The 4-week induction period was followed by 44 weeks of 9 mg TIW Interferon alfacon-1 therapy and up to 24 weeks of observation. Serum HCV RNA was quantified by RT-PCR (lower sensitivity, 100 copies/mL). There were no significant differences in baseline characteristics among the groups at baseline.

The table below reports the viral response rates by treatment group as well as baseline viral titer at the end of the induction period, end of treatment and end of observation (sustained response rates). Daily induction treatment followed by 9 mg Interferon alfacon-1 thrice weekly resulted in sustained HCV RNA response rates of 5.4 - 28.1%. Subjects with low baseline titers had a greater sustained HCV RNA response rate (10 - 55.6%) compared to subjects with high baseline titers (3.7 - 21.4%).

Although at the end of induction there were significant differences among the treatment groups in the reduction of serum HCV RNA, there were no differences in the sustained viral response rate. Viral rebound after induction was observed in the daily induction groups. Dose reductions and discontinuations were more frequent in the 7.5 mg BID group. The most common reason for dose reduction and the discontinuation of therapy was depression.

Conclusions:

1) Four weeks of daily Interferon alfacon-1 induction therapy followed by 44 weeks of 9 mg TIW did not result in a greater sustained HCV RNA response rate in comparison to 9 mg TIW alone.

(2) However, sustained viral response following 48 weeks of therapy was associated with a higher sustained viral response than what was previously observed with 24 weeks of therapy.

(3) Viral rebound after four weeks of daily induction therapy suggests that an extended daily regimen coupled with higher maintenance regimen needs to be evaluated for even better sustained viral response rates.

Viral Response Rates by Induction Regimen and Baseline Viral Titer:

Treatment Group End of Induction
(week 4)
End of Treatment
(week 48)
End of Observation
(week 72)
15g QD (n=37) 15 (40.5%) 8 (21.6%)  2 (5.4%)
Low (n=10)         8 (80.0%) 2 (20.0%) 1 (10.0%)
High (n=27)        7 (25.9%) 6 (22.2%) 1   (3.7%)
7.5g BID (n=36) 14 (38.9%) 7 (19.4%) 6 (16.7%)
Low (n=10)         7 (70.0%) 3 (30.0%) 3 (30.0%)
High (n=26)        7 (26.9%) 4 (15.4%) 3 (11.5%)
15g TIW (n=34) 12 (53.3%)  13 (38.2%)    9 (26.5%)
Low  (n=9)          5 (55.6%) 5 (55.6%) 5 (55.6%)
High (n=25)        7 (28.0%) 8 (32.0%) 4 (16.0%)
9g QD (n=32) 12 (37.5%)  14 (43.8%)    9 (28.1%)
Low (n=12)         7 (58.3%) 7 (58.3%) 5 (41.7%)
High (n=20)        5 (25.0%) 7 (35.0%) 4 (20.0%)
9g TIW (n=39)  6 (15.4%)  14 (35.9%)    10 (25.6%)   
Low (n=11)         4 (36.4%) 5 (45.5%) 4 (36.4%)
High (n=28)        2  (7.1%)   9 (32.1%) 6 (21.4%)