A prospective, randomized trial comparing lymphoblastoid to recombinant interferon alfa 2a as therapy for chronic hepatitis C

Abstract

the development of IFN-neutralizing antibodies. [12][13][14] TheoretTo compare the long-term effectiveness and tolerabilically, these risks might be enhanced by long-term adminity of lymphoblastoid interferon (IFN-aN1) and recombiistration of a single type of IFN and mitigated by the adminnant interferon alfa 2a (IFN-a2a) in patients with istration of different types of IFN. Lymphoblastoid IFN chronic hepatitis caused by hepatitis C virus (HCV), 234 (IFN-aN1), a mixture of 22 interferons, 15 was shown to induce consecutive patients with HCV-related chronic hepatitis a response in 40% of nonresponders to recombinant IFN 16,17 were randomized prospectively to receive titrated doses and resulted in a complete response in all patients with hepa-(starting dose Å 6 million units [MU]) of IFN-a2a (n Å titis C who relapsed during treatment with recombinant 118) or IFN-aN1 (n Å 116) for 12 months. HCV RNA was IFN. 14 To assess whether treatment of hepatitis C can be detected by reverse-transcription polymerase chain reimproved by using lymphoblastoid IFN, we have conducted action (RT-PCR), quantified by branched-DNA (bDNA) a prospective randomized comparative trial in which patients assay, and genotyped by reverse hybridization assay.with chronic hepatitis caused by HCV were randomized to Thirty-one patients in the IFN-a2a group and 28 in the either recombinant IFN-a2a or lymphoblastoid IFN-aN1. IFN-aN1 group (total, 59 [25%] had normal transami-To avoid potential bias caused by insufficient dose or duranases and undetectable HCV RNA by RT-PCR after 12 tion of therapy, we elected to treat patients for 12 months months of therapy, but only 19 in the first group and 20and modify the dose according to the alanine transaminase in the second group (total, 39 [17%]) had biochemical (ALT) response. The initial dose was 6 MU. To gain insight and virological responses 12 months after treatment was on the cost-effectiveness of treatment regimens, we analyzed discontinued. The two treatment groups differed in the tolerability and cost of the two treatments, as well as terms of prevalence of major drug-related adverse reacclinical and virological predictors of treatment outcome that tions (23% vs. 37%, P Å .025). The mean total dose per could be used for refining therapy duration or dosage. size made it possible to perform an interim analysis when 50% of the patients had been enrolled. It was planned that the trial would Less than 25% of the patients with chronic hepatitis C be discontinued at that time if the difference in response rates beachieve sustained biochemical responses with undetectable se-tween the two treatments was outside the confidence interval (CI) related to a type I error equal to 0.025 (3.8%-36.2%). and longer duration of therapy have been attempted to in-ies, and abnormal serum transaminase levels. Enrollment was crease the response rates, but the data are inconclusive. [4][5][6][7][8][9] stopped in November 1992 when 258 patients had been recruited, Nonresponse or loss of response during IFN therapy could and...

Hepatitis C reactivation in patients with chronic infection with genotypes 1b and 2c: a retrospective cohort study of 206 untreated patients

“…Genotypes 1a, 3a, and 4 together accounted for less than 20% of patients attending our centre in the 1990s. 19 Patients were also excluded if they had serum hepatitis B surface antigens (HBsAg), daily alcohol intake .60 g for men and .40 g for women, serum antibodies to human immunodeficiency virus, or autoimmune liver disease. Definition of ALT flare An ALT flare was arbitrarily defined as an ALT value >400 IU/l or a maximum/minimum ALT ratio value of >8.…”

Hepatitis C, interferon alfa, and depression

“…The rate of depression has varied substantially across different studies possibly reflecting variation in dosing schedules or in the composition of study cohorts. [27][28][29][30][31][32][33][34][35][36][37] Also, the duration of therapy may play a role. 23,27,32,33,35 Study groups may vary in the proportion of patients with depression.…”

Treatment strategies for chronic hepatitis C: Update since the 1997 National Institutes of Health Consensus Development Conference

“…Recent trials have shown convincingly that, similar to other interferons, 21 the optimal duration for treatment with IFNα‐n1 is 12 months rather than 6 months 22 . Although higher doses of some recombinant IFNα have been reported to improve treatment outcomes slightly, 21 –23 this may not be the case for IFNα‐n1 and doses higher than 3 MIU, three times weekly, when administered for 12 months, are associated with an increased rate of adverse effects 24 , 25 …”