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At least 181 records · Page 10Linked to original sources
PubMed2005

A randomized controlled trial of pegylated interferon alpha-2a (40 KD) or interferon alpha-2a plus ribavirin and amantadine vs interferon alpha-2a and ribavirin in treatment-naïve patients with chronic hepatitis C.

We determined whether triple therapy comprising amantadine (AMA), ribavirin (RBV) and either peginterferon (PEG-IFN) alpha-2a or conventional IFN alpha-2a would improve sustained virological response (SVR) rates over dual therapy with IFN alpha-2a and RBV in patients with chronic HCV infection. A total of 362 treatment-naïve patients were randomized to 48 weeks of treatment with: PEG-IFN alpha-2a 180 microg/week (group A) or IFN alpha-2a 3 MU tiw (groups B and C). All patients received RBV 1000 or 1200 mg/day and those in groups A and B received AMA 200 mg/day. SVR was defined as an undetectable HCV RNA after 24 weeks of untreated follow-up. At the end of therapy, 74.4% (95% CI 0.66-0.82) of patients in group A were HCV RNA-negative compared with 42.5% (95% CI 0.33-0.50) of those in group B (P = 0.0001) and 48.8% (95% CI 0.40-0.56) of those in group C. SVR was achieved in a significantly greater proportion of patients in group A compared with groups B and C: 65.3% (95% CI 0.53-0.56), 33.3% (95% CI 0.25-0.41) and 44.6% (95% CI 0.36-0.53; P = 0.0001) respectively. In patients with genotype 1, SVR rates were 55.2, 22.8 and 28.8% with the three regimens respectively. Factors independently associated with SVR were HCV genotype 2 or 3, therapy with PEG-IFN, female gender and age. In treatment-naive patients with chronic hepatitis C, triple therapy with PEG-IFN alpha-2a, RBV and AMA produces higher SVR than dual or triple therapy with conventional IFN alpha-2a.

Adolescent↗
PubMed1995

Recombinant duck interferon: a new reagent for studying the mode of interferon action against hepatitis B virus.

Although interferon is widely used to treat chronic hepatitis B virus infections, its mode of action against hepadnaviruses is largely unknown. This deficit is due mainly to the lack of suitable model systems. The duck system could not be used because purified duck interferon was not available in sufficient quantities. We have now cloned a DNA fragment that contains an intronless gene for duck interferon. The primary translation product consists of 191 amino acids, the N-terminal 30 residues of which constitute a signal peptide. Mature duck interferon is 50% identical to the recently cloned chicken interferon. Sequence homology to mammalian interferons is marginal, but conservation of four cysteine residues and inducibility by virus indicate a distant relationship between duck interferon and mammalian type I interferons. Purified recombinant duck interferon from Escherichia coli is biologically active: it activates the interferon-inducible Mx gene, prevents cell destruction by cytolytic RNA viruses, and has a strong inhibitory effect on duck hepatitis B virus in cultured primary duck hepatocytes. This new reagent should help to define the interferon-sensitive step of the hepadnavirus life cycle. Furthermore, the duck system can now be used for systematic studies of the in vivo effectiveness of interferon in chronic hepatitis B virus infections.

Amino Acid Sequence↗
PubMed1986

Interferon modulation of c-myc expression in cloned Daudi cells: relationship to the phenotype of interferon resistance.

Treatment of interferon-sensitive Daudi cell with electrophoretically pure human interferon alpha markedly reduced the level of c-myc mRNA, increased the level of class I histocompatibility antigen (HLA) mRNA, and did not affect the level of actin mRNA within the same cells. In contrast, the level of c-myc mRNA or HLA mRNA did not change significantly following interferon treatment in different clones of Daudi cells selected for resistance to the antiproliferative action of interferon. These cells possessed interferon receptors, however, and responded to interferon modulation of other genes, including 2',5' oligoisoadenylate synthetase (M. G. Tovey, M. Dron, K. E. Mogensen, B. Lebleu, N. Metchi, and J. Begon-Lours, Guymarho, J. Gen. Virol., 64:2649-2653, 1983; M. Dron, M. G. Tovey, and P. Eid, J. Gen. Virol., 66:787-795, 1985). A clone of interferon-resistant Daudi cells which had reverted to almost complete sensitivity to both the antiproliferative action of interferon and the interferon-enhanced expression of HLA mRNA remained refractory, however, to interferon modulation of c-myc expression, suggesting that a reduced level of c-myc mRNA may not be a prerequisite for inhibition of cell proliferation in interferon-treated cells. Our results do not exclude the possibility, however, that posttranscriptional modification(s) of c-myc expression may precede an inhibition of cell proliferation in interferon-treated cells.

Cell Line↗
PubMed1984

The kinetics of interferon clearance in mice: comparison of mouse and human interferon.

Mice were injected with three kinds of interferon, i.e., mouse, human leucocyte and human fibroblast interferon, and the kinetics of their clearance from the blood was compared. After intravenous injection, mouse interferon was cleared very rapidly with an initial half life to two to three minutes, while both types of human interferon were cleared rather slowly with a corresponding value of about 20 minutes. When mouse interferon was injected intramuscularly or intraperitoneally, only very low levels of interferon activity were detected in the serum, and the recovery did not exceed 1% at any time. In contrast, both types of human interferon gave appreciable levels of activity in the serum upon injection by the same routes, and the levels remained stable during the observation period. The recovery of human interferon in the blood was about 10-fold that of mouse interferon. Mouse interferon was not inactivated in vitro by incubation with normal mouse serum. Our results suggest the validity of using homologous interferon for studies on the kinetics of interferon clearance in experimental animals.

Animals↗
PubMed1997

Interferon regulatory factor 1 induces the expression of the interferon-stimulated genes.

The interferon regulatory factor 1 (IRF-1) is a positive transcriptional regulatory protein which acts in the interferon signal transduction pathway to activate the transcription of the type I interferon genes by binding to the PRDI response element. The aim of this study was to explore the role of IRF-1 in regulating the expression of other interferon-stimulated genes in the interferon signal transduction pathway. A transient transfection assay was used to show that IRF-1 induced the expression of interferon-stimulated genes. The induction was a direct result of IRF-1 binding to the promoters of the interferon-stimulated response element (ISRE). The levels of endogenous mRNA of two interferon-stimulated genes, 6-16 and 9-27, were increased in cells containing increased levels of IRF-1. In addition, IRF-1 activates the expression of IRF-2, a negative regulator of the type I interferon genes themselves. Two sequences were found in the IRF-2 promoter which were the binding sites for IRF-1. Mutations in the oligonucleotide sequences of these sites could abolish the binding of the IRF-1. These data suggested that IRF-1 not only plays an important role in the induction of type I interferon genes, but also in the activation of interferon-stimulated genes.

Base Sequence↗
PubMed1995

The myxoma virus-soluble interferon-gamma receptor homolog, M-T7, inhibits interferon-gamma in a species-specific manner.

The myxoma virus M-T7 protein contains significant sequence similarity to the ligand binding domain of the mammalian interferon-gamma receptors, and functions as a soluble homolog which can bind and inhibit the biological activities of rabbit interferon-gamma (Upton, C., Mossman, K., and McFadden, G. (1992) Science 258:1369-1372). M-T7, the most abundantly secreted protein from myxoma virus-infected cells, was shown to be expressed in significant biological amounts as a typical poxvirus early gene product, efficiently secreted at early times of infection to levels that exceed 5 x 10(7) molecules/cell, and function as a stable inhibitory protein in infected cell supernatants until late times of infection. M-T7 was specific in binding and inhibiting rabbit interferon-gamma, and did not bind either human or murine interferon-gamma. Scatchard analysis of rabbit interferon-gamma binding curves yielded a single high affinity binding site on M-T7, with a Kd of 1.2 x 10(-9) M, which is comparable to the affinity between soluble forms of cellular interferon-gamma receptors and their cognate ligands. In comparison, rabbit interferon-gamma was shown to bind its cellular receptor with a Kd of 5.9 x 10(-10) M, again comparable to the affinity of membrane bound forms of other mammalian interferon-gamma receptors for interferon-gamma. Thus, the myxoma virus M-T7 protein is a functional soluble interferon-gamma receptor homolog which binds and inhibits interferon-gamma with high affinity in a species-specific manner.

Amino Acid Sequence↗
PubMed2002

[Interferon alfacon-1 (Advaferon): a novel synthetic interferon for the treatment of hepatitis C, its pharmacological and clinical profile].

Interferon alfacon-1 (Advaferon, also referred to as consensus interferon) is a novel synthetic recombinant type-I interferon (IFN) developed by comparing the amino acid sequences of several natural IFN-alpha subtypes and assigning the most frequently observed amino acid in each corresponding position to generate a consensus molecule. Interferon alfacon-1 binds with high affinity to type-I IFN receptors and has greater biological activity than naturally occurring IFN-alpha as assessed by its increased antiviral, anti-proliferative, and natural killer cell activities, as well as its stronger IFN-stimulated gene induction. In a multicenter, randomized, controlled study, the safety and efficacy of interferon alfacon-1 in comparison with lymphoblastoid interferon-alpha [IFN-alpha (NAMALWA)] was evaluated in patients infected with high-titer chronic hepatitis C virus (HCV). Interferon alfacon-1 (18 MIU) was superior in efficacy without additional toxicity to IFN-alpha (NAMALWA) (9 MIU) in high-titer chronic HCV patients, particularly those infected with genotype 1b. A multicenter open-label study showed that treatment with interferon alfacon-1 (12 MIU) was an effective and tolerable therapy in chronic HCV patients with low viral titers. Another multicenter open-label study showed that re-treatment with interferon alfacon-1 (18 MIU) was an effective and tolerable therapy in chronic HCV patients who relapsed after traditional IFN therapy. Collectively, these clinical studies indicate that interferon alfacon-1, as a novel synthetic interferon, may be a useful therapeutic alternative for the effective treatment of hepatitis C.

Adjuvants, Immunologic↗
PubMed1990

Interferon antibodies may negate the antiviral effects of recombinant alpha-interferon treatment in patients with chronic hepatitis B virus infection.

In a randomized controlled trial of recombinant alpha-2a interferon for chronic hepatitis B, interferon antibodies developed in 21 (39%) of 54 Chinese adults who received IFN. No correlation was observed between sex, age, pretreatment serum ALT level or liver histological findings and the development of interferon antibodies. Antibodies were significantly more likely to develop in patients who received lower doses (2.5 or 5 MU/m2) of alpha-2a interferon than in those who received a higher dose (10 MU/m2): 53% vs. 11% (p = 0.006). The development of interferon antibodies appeared to reverse the initial antiviral response to treatment, with reappearance of hepatitis B virus DNA in serum in 12 patients and HBeAg in three patients. Sustained clearance of HBeAg was achieved in only one (5%) patient but was achieved in seven (21%) patients without interferon antibodies. The mere presence of interferon antibodies did not preclude an antiviral response to interferon therapy, but patients with high titer neutralizing antibodies were less likely to respond. These findings suggest that interferon antibodies may negate the antiviral effects of alpha-2a interferon. A higher incidence of interferon antibodies in Chinese vs. white patients with chronic hepatitis B may contribute to the poorer antiviral response in Chinese patients.

Adult↗
PubMed1991

High doses of recombinant alpha-interferon or gamma-interferon for chronic hepatitis C: a randomized, controlled trial.

Chronic hepatitis C is often a progressive liver disease for which there is no satisfactory treatment. We studied the efficacy of recombinant alpha-interferon or gamma-interferon in the treatment of this disease in comparison with a control group. Thirty patients were randomly assigned to three groups. Ten patients received 7.5 MU alpha-interferon/m2 body surface three times weekly for 3 mo, then 5 MU/m2 for 3 mo and 2.5 MU/m2 for 6 mo. Ten patients were treated with gamma-interferon at a dose of 2 MU/m2 for 6 mo and the other 10 served as controls without treatment. The mean serum ALT levels and liver histological findings improved significantly only in the patients treated with alpha-interferon. No changes were observed in patients treated with gamma-interferon or in controls. Five of 10 patients treated with alpha-interferon had complete responses (mean ALT normal during therapy). After treatment ALT returned to pretreatment levels in two of 5 patients. The long-term response rate after alpha-interferon therapy was 30% at 18 mo. We conclude that alpha-interferon is effective in controlling disease activity in a portion of patients with chronic hepatitis C. High doses of alpha-interferon do not appear to add further benefit in the response rate or relapse rate. gamma-Interferon therapy is ineffective.

Adult↗
PubMed2001

Interferon regulatory factor 1 promoter polymorphism and response to type 1 interferon.

The clinical success of interferon-treatment has been found to vary in different individuals. To explain this, we hypothesized that responses to type 1 interferons could be partly determined by interferon regulatory factor-1 gene transcription, because the latter is an important transcription factor in the interferon system. We demonstrated that the antiproliferative effect of type 1 interferons on human liver cancer cells correlates with levels of transcription of the interferon regulatory factor-1 gene in parallel with those of p21(WAF-1) expression. Here, we investigated whether mutations in the interferon regulatory factor-1 gene cause different responses to type 1 interferons. DNA from several human liver cancer cell lines and peripheral blood mononuclear cells was investigated. Nucleotide sequences of the interferon regulatory factor-1 gene and polymerase chain reaction products of its upstream region were determined directly and after cloning. The promoter activity of the upstream region of this gene was measured by the luciferase reporter assay. We found 4 point mutations in the upstream (- 1 approximately - 495) region, and the luciferase promoter assay demonstrated that these mutations did modify promoter activity. Analysis of DNA from healthy volunteers showed that these mutations are single nucleotide polymorphisms. These results suggest that single nucleotide polymorphisms of the interferon regulatory factor-1 promoter contribute, at least in part, to determining responses to type 1 interferons. J. Cell. Biochem. Suppl. 36: 191-200, 2001.

Antineoplastic Agents↗
PubMed1991

Interferon-beta specifically inhibits interferon-gamma-induced class II major histocompatibility complex gene transcription in a human astrocytoma cell line.

We established cultures of human astrocytes and astrocytoma cells from surgical specimens, to study regulation of class II major histocompatibility (MHC) complex antigen expression by interferons. Using these cultures we previously showed that expression of the class II MHC determinant HLA-DR could be induced by interferon-gamma and this induction was inhibited by interferon-beta. In this report, we extend these observations by showing that the inhibitory effect of interferon-beta on interferon-gamma induction of the class II MHC gene HLA-DR alpha was exerted at the transcriptional level, as documented by nuclear run-on experiments and confirmed with blot hybridization analysis. Astrocyte expression of intercellular adhesion molecule-1 (ICAM-1) was induced efficiently by interferon-gamma, but not by interferon-beta, and induction of ICAM-1 expression by interferon-gamma could not be impaired by interferon-beta, suggesting that the suppressive effect on induction of HLA-DR was relatively gene-specific. Furthermore, interferon-beta did not antagonize interferon-gamma induction of HLA-DR expression in human monocytes, suggesting that the inhibition observed in astrocytes was relatively tissue-specific.

Astrocytes↗
PubMed1999

Interferon alpha-2B and ribavirin in combination for patients with chronic hepatitis C who failed to respond to, or relapsed after, interferon alpha therapy: a randomized trial.

PURPOSE: To assess the efficacy of interferon alpha-2b and ribavirin in combination in the treatment of patients with chronic hepatitis C who had either failed to respond to therapy with interferon alpha (nonresponders), or who had relapsed after interferon therapy (relapsers). SUBJECTS AND METHODS: Four hundred patients with chronic hepatitis C (200 nonresponders and 200 relapsers) were randomly assigned in equal numbers to receive either subcutaneous administration of recombinant interferon alpha-2b (3 million units three times per week) and ribavirin (1,000 to 1,200 mg/daily orally) or interferon alpha-2b alone (6 million units three times per week). Both ribavirin and interferon alpha-2b were given for 24 weeks. The patients were then followed for an additional 24 weeks. RESULTS: At the end of the treatment period, normalization of serum alanine aminotransferase levels and absence of hepatitis C virus RNA were seen in 21% of nonresponders and in 39% of relapsers who were treated with interferon alpha-2b and ribavirin, compared with 5% of nonresponders (P = 0.001) and 9% of relapsers treated with interferon alpha-2b alone (P <0.001). At the end of follow-up, 14% of nonresponders and 30% of relapsers treated with the combination therapy had a sustained response, compared with 1% of nonresponders (P = 0.001) and 5% of relapsers treated with interferon alpha alone (P <0.001). CONCLUSIONS: A 24-week course of treatment with interferon alpha-2b and ribavirin offers a chance of sustained response, whereas retreatment with interferon alpha-2b alone does not give satisfactory results. The role of long-term therapy in inducing prolonged remission remains to be explored.

Adolescent↗
PubMed2000

Early addition of ribavirin to interferon in chronic hepatitis C not responsive to interferon monotherapy.

BACKGROUND/AIM: Persistence of HCV-RNA in serum early in treatment is a strong predictor of failure of alpha-interferon therapy for chronic hepatitis C. Therefore, we compared the efficacy of ribavirin addition to alpha-interferon with a doubling of the dosage of alpha-interferon in case of lack of early virological response to alpha-interferon therapy. METHODS: Sixty patients were administered interferon alpha2b at the dosage of 3 million units 3 times a week. After the first 4 weeks of therapy, serum HCV-RNA was evaluated. The patients with negative HCV-RNA test received the same treatment for a further 11 months, while those with detectable HCV-RNA were randomized to receive either the same dosage of alpha-interferon plus ribavirin (1000 mg/day) or double dosage of alpha-interferon (6 million units tiw) for 11 months. We considered sustained response to be the maintenance of normal alanine aminotransferase and negativity at HCV-RNA testing until the end of a 6-month post-treatment follow-up. RESULTS: After the first 4 weeks of treatment, 12 (20%) patients showed virological response and 48 patients (80%) remained positive on HCV-RNA testing. Sustained response was observed in 5/12 (42%) patients with early virological response, in 10/24 (42%) patients without early virological response who were administered ribavirin and alpha-interferon, and in only 1/24 (4%) patients who were administered the double dosage of alpha-interferon (p=0.006). CONCLUSIONS: This study shows the efficacy of the addition of ribavirin to alpha-interferon and the lack of efficacy of doubling the dosage of alpha-interferon in patients without clearance of hepatitis C virus early on in treatment.

Adult↗
PubMed2002

Daily or three times a week interferon alfa-2b in combination with ribavirin or interferon alone for the treatment of patients with chronic hepatitis C.

BACKGROUND/AIMS: Data on hepatitis C virus (HCV) viral dynamics and on the effect of interferon in blocking virion production have suggested a rationale for daily administration of interferon in patients with chronic hepatitis C infection. We compared the efficacy and safety of daily interferon alfa-2b in combination with ribavirin with those of interferon alfa-2b three times a week alone or in combination with ribavirin. METHODS: We randomly assigned 321 patients with chronic hepatitis C to receive standard-dose interferon alfa-2b alone or in combination with ribavirin for 48 weeks or daily interferon alfa-2b (3 million units per day for 12 weeks then 3 million units three times per week for 24 weeks) and ribavirin (36 week treatment). RESULTS: The rate of sustained virologic response (defined as an undetectable serum HCV-RNA level 72 weeks after initiation of treatment) was higher in patients who received combination therapy with three times weekly interferon (51.7%) or daily interferon (46.1%) than in patients who received interferon alone (25%) (P=0.0001 and P=0.002, respectively). Independent predictive factors for sustained virologic response were combination therapy, weight, genotype and viral load. In conclusion, in patients with chronic hepatitis C, combination therapy with induction treatment (daily interferon for 12 weeks) and shorter duration of treatment was not different from combination therapy for 48 weeks without induction treatment. CONCLUSIONS: Induction treatment with interferon for 12 weeks and combination therapy for a total duration of 36 weeks could therefore be cost effective.

Adult↗
PubMed1999

A randomized trial of ribavirin and interferon-alpha vs. interferon-alpha alone in patients with chronic hepatitis C who were non-responders to a previous treatment. Multicenter Study Group under the coordination of the Necker Hospital, Paris, France.

BACKGROUND/AIM: Fifty percent of patients infected with hepatitis C virus (HCV) show no response to alpha-interferon, and no alternative therapy has thus far proven to be effective. Therapeutic combination with ribavirin and alpha-interferon has shown promising results in naive patients and in relapsers, but based on limited series, it was reported to be inefficient in non-responders. The aim of our study was therefore to explore and compare, in a randomized trial, the tolerance and potential efficacy of alpha-interferon alone with a sequential combination of ribavirin and the same alpha-interferon regimen in those patients. METHODS: Sixty-four non-responder patients were randomized in the alpha2b-interferon group (a 6-month course at a dosage of 6 MU followed by a 6-month course of 3 MU three times weekly subcutaneously) and 62 in the "combination" group (sequential combination of the same alpha2b-interferon therapy preceded by a 2-month course of ribavirin which was then associated for 2 months with alpha2b-interferon at a daily dosage of 1.0 or 1.2 g). RESULTS: Treatment withdrawal was necessary for six patients from the alpha-interferon and eight patients from the combination group. Normalization of aminotransferase activities was significantly more frequent after the 4-month course of ribavirin with 2 months of interferon than after 2 months of interferon alone (52.8 vs. 26.2%, p<0.01), but this difference was not maintained after ribavirin withdrawal. Disappearance of serum HCV RNA (PCR) was significantly more frequent at the end of treatment in the combination group (24.5 vs. 7.7%, p=0.02), but did not differ 6 months after the end of therapy (9.8 and 8.3%, respectively). The long-term response was not associated with liver status (cirrhosis vs. absence of cirrhosis) or genotype. Mean viremia was significantly lower in long-term responders than in non-responders or relapsers in both groups (p<0.001 for the interferon group and p<0.05 for the combination group), but the large extent of viral load precluded reliable prediction. The pre- and post-treatment hepatitis activity index did not differ between the two groups. While a crude histopathological improvement in the hepatitis activity index for a given patient was more frequently observed in the combination group (69.2 vs. 35.9%, p<0.01), improvement as defined by a decrease of at least 2 in the hepatitis activity index was significant only for lobular necrosis and degeneration. CONCLUSIONS: This study demonstrates the efficacy of the combination of ribavirin/alpha-interferon in non-responders. Indeed, (i) it is fairly tolerated; (ii) it increases the rate of the initial biological response, and of the virological response by decreasing breakthrough, though this benefit is not sustained; and (iii) it induces a significant histological improvement in necrosis. A simultaneous and prolonged combination of ribavirin/alpha-interferon should be further evaluated in non-responders.

Antiviral Agents↗
PubMed2003

Expression modes of interferon-alpha inducible genes in sensitive and resistant human melanoma cells stimulated with regular and pegylated interferon-alpha.

Interferon-alpha with its antiproliferative activity is widely used for the treatment of viral infections and tumor therapy such as melanoma. Naturally occurring resistance to recombinant interferon alpha-2a (IFN-alpha) and severe side effects limit the therapeutic efficacy. Understanding of the molecular mechanisms involved in unresponsiveness may therefore lead to the development of novel formulations that overcome resistance. Here, we have applied oligonucleotide DNA microarrays with probe sets for about 11,400 human transcripts to study the expression of interferon-alpha inducible genes in a sensitive and resistant melanoma cell line over multiple time points and two interferon formulations. We identified two major groups of genes with termed interferon primary response genes (IPRGs) or interferon secondary response genes (ISRGs). IPRGs are upregulated early after interferon stimulation in both the sensitive and the resistant line and they contain IREs in the noncoding regulatory region. In contrast, ISRG expression occurs preferentially in the sensitive line ME15 at late time points, and this group of genes lacks typically IREs. In addition to these two major interferon response gene classes, we identified a relatively small number of genes with complex kinetic expression modes. In addition, we show for the first time that regular and pegylated recombinant interferons are equally potent activators of interferon (IFN) gene expression. Finally, we propose that the ISRGs are activated downstream of the primary response genes by a molecule or pathway, which awaits identification, and interferon inducible gene expression is thus more complicated than previously thought.

Drug Resistance, Neoplasm↗
PubMedDate not supplied

Rational design of a potent, long-lasting form of interferon: a 40 kDa branched polyethylene glycol-conjugated interferon alpha-2a for the treatment of hepatitis C.

A potent, long-lasting form of interferon alpha-2a mono-pegylated with a 40 kilodalton branched poly(ethylene glycol) was designed, synthesized, and characterized. Mono-pegylated interferon alpha-2a was comprised of four major positional isomers involving Lys31, Lys121, Lys131, and Lys134 of interferon. The in vitro anti-viral activity of pegylated interferon alpha-2a was found to be only 7% of the original activity. In contrast, the in vivo antitumor activity was severalfold enhanced compared to interferon alpha-2a. Pegylated interferon alpha-2a showed no immunogenicity in mice. After subcutaneous injection of pegylated interferon alpha-2a, a 70-fold increase in serum half-life and a 50-fold increase in mean plasma residence time concomitant with sustained serum concentrations were observed relative to interferon alpha-2a. These preclinical results suggest a significantly enhanced human pharmacological profile for pegylated interferon alpha-2a. Results of Phase II/III hepatitis C clinical trials in humans confirmed the superior efficacy of pegylated interferon alpha-2a compared to unmodified interferon alpha-2a.

Animals↗