Efficacy Of Peginterferon Alpha-2a Research Articles

Indirect comparison of the antiviral efficacy of peginterferon alpha 2a plus ribavirin used with or without simeprevir in genotype 4 hepatitis C virus infection, where common comparator study arms are lacking: a special application of the matching adjusted indirect comparison methodology

Background:The need to assess relative efficacy in the absence of comparative clinical trials is a problem that is often encountered in economic modeling. The use of matching adjusted indirect comparison (MAIC) in this situation has been suggested. We present the results of a MAIC used to evaluate the incremental benefit offered by adding simeprevir (SMV) to standard therapy in the treatment of patients infected with genotype 4 hepatitis C virus (HCV).Methods:Individual patient data for a single arm study evaluating the use of SMV with peginterferon alfa 2a + ribavirin (PR) in genotype 4 HCV were available (RESTORE study). A systematic literature review was used to identify studies of PR alone used in the same patient group. By applying the inclusion criteria for each study in turn to the RESTORE dataset and then applying the published MAIC covariate matching algorithm, a series of pseudosamples from RESTORE were generated. After assessment of the matching outcomes, the best matched comparisons were used to derive estimates of efficacy for SMV + PR in patients equivalent to those participating in the PR trial.Results:Five potential comparator studies were identified. After applying the matching process, two emerged as offering the greatest equivalence with the generated RESTORE pseudosamples and were used to estimate SMV + PR efficacy, expressed as the percentage of patients achieving sustained viral response (SVR). In one comparison, SVR in the SMV + PR group was 85% versus 63% for PR alone. In the second comparison, the corresponding SVRs were 77% and 44% respectively.Conclusions:After matching for varying baseline characteristics, both comparisons of RESTORE versus studies of PR alone yielded a benefit for SMV + PR vs PR alone in genotype 4 HCV-infected patients. The incremental gain in SVR associated with use of SMV ranged from 22% to 33%. In the absence of direct comparative studies, the MAIC gives a better perspective than simple comparison of absolute SVR from individual studies.

Efficacy and Tolerability of Peginterferon alpha-2a and Peginterferon alpha-2b in Iranian Patients With Chronic Hepatitis C.

Background:Nearly 0.5% of Iranians are infected with HCV. Peginterferon-alpha-2a and Peginterferon-alpha-2b are the two available types of interferon for the treatment of hepatitis C. Comparing the results of these two treatments is still a challenge.Objectives:The aim of this study was to compare the results of Peginterferon-alpha-2a and Peginterferon-alpha-2b in Iranian patients with chronic hepatitis C.Patients and Methods:289 patients with chronic hepatitis C attending Tehran Hepatitis Center (THC) and Hepatitis Clinic of Tehran Blood Transfusion Organization (TBTO) from January 2008 to April 2013 and treated with combination of Peginterferon-alpha-2a or Peginterferon-alpha-2b plus Ribavirin were enrolled in this retrospective cross-sectional study. Treatment response and side effects were compared.Results:Among all naive patients, 82.0% achieved SVR, 5.4% were resistant to therapy and 11.0% withdrew the treatment. Relapse was seen in 12.2% of naive patients who finished the course of treatment. RVR and EVR were seen in 67.7% and 90.6% of naive patients, respectively. Patients divided into two groups. Group A consists of 247 patients treated with Peginterferon-alpha-2a and group B 42 patients treated with Peginterferon-alpha-2b. No significant difference in treatment response was observed between naive patients of the two groups. The rates of arthralgia/myalgia, alopecia, pruritus, insomnia, dyspnea and anorexia were higher in group A and the rates of dermal problems, coryza and bleeding were higher in group B. In a subgroup analysis, the two kinds of Peginterferon-alpha-2a available in Iran were compared. Rapid and early viral responses and relapse rates were lower in the one made in Iran and the long-term responses were not different. The rates of arthralgia/myalgia, fever, alopecia, pruritus, insomnia, dyspnea, anorexia, cough, headache and abdominal pain were higher and the rates of irritability and coryza were lower in the one made in Iran.Conclusions:There was no significant difference in the efficacy of Peginterferon-alpha-2a and Peginterferon-alpha-2b in Iranian patients. Physicians might choose the treatment regimen for every individual concerning the differences in side effects of Peginterferons.

Efficacy of Peg-interferon alpha-2a combinated with entecavir on HBeAg positive chronic hepatitis B patients with high serum hepatitis B viral loads

This study aimed at evaluating the efficacy and safety of a combination treatment of entecavir and Peginterferon alpha-2a for HBeAg positive chronic hepatitis B patients with high serum hepatitis B viral loads. 60 treatment-naive HBeAg-positive CHB patients with high serum hepatitis B viral loads were enrolled and randomly divided into three groups: group A received Peginterferon alpha-2a monotherapy for 48 weeks (n = 20); group B received entecavir monotherapy for more than 48 weeks (n = 20); group C received Peginterferona alpha-2a combined with entecavir for 12 weeks, then Peginterferon alpha-2a monotherapy for 36 weeks (n = 20). Virological response, ALT normalization, HBeAg and HBsAg seroclearance rate were analysed at the end of 4, 12 and 24 weeks after the treatment. The ratio of undetectable hepatitis B virus (HBV) DNA were 50% and 10%, 95% and 25% and 100% and 30% in group C and group A respectively, 50% and 20%, 95% and 75% and 100% and 90% in group C and group B respectively at the end of 4, 12 and 24 weeks of treatment. The differences were significant between group C and A (Z = -4.6, P < 0.001), group C and B (Z = -2.53, P = 0.0114). ALT normalization rate was significantly lower in group A than that of group C (Z = -2.63, P = 0.0086). HBeAg levels declined more in group C than the other two groups after 24 weeks of treatment. For HBeAg positive chronic hepatitis B patients with high serum hepatitis B viral loads, combination treament of Peginterferon alpha-2a with entecavir is more effective than Peginterferon alpha-2a monotherapy in virologic response and ALT normalization after 24 weeks of treatment.

Efficacy of peg interferon alpha-2a in combination with ribavirin in treatment of with hepatitis C cirrhosis patients

To study the clinical efficacy of PEG Interferon alpha-2a combined with ribavirin in treatment of with hepatitis C cirrhosis patients. 21 patients with chronic hepatitis C cirrhosis (treated group) ,were treated with peg-IFNalpha-2a 135 -180 microg subcutaneously, 1 week,ribavirin tablets 800 -1000 mg/d,48 weeks of treatment and follow-up 24 weeks, 20 patients with Chronic hepatitis C (control group), were treated with peg-IFNalpha-2a 135 -180 microg subcutaneously, 1 week,ribavirin tablets 600 -1000 mg/d, 48 weeks of treatment, follow-up 24 weeks, comparison of rapid virological response (RVR) rates, early virologic response (EVR) rate, sustained virologic response (SVR) rate, adverse reactions was observed. The differences of RVR, EVR, ETVR in two groups is not significant, but SVR in treatment group was lower (P < 0.05), and has a higher incidence bone marrow suppression and anemia (P < 0.05). Flu-like symptoms, hair loss, gastrointestinal reactions and other adverse reactions was no significant difference between the two groups. The use of 135 microg peg-IFNalpha-2a and individual in low-dose ribavirin hepatitis C patients with cirrhosis is more security,could get a good early response, but sustained virologic response (SVR) rates is lower than hepatitis C patients. Blood, liver and kidney function should be closely observed during treatment process.

Efficacy of peginterferon alpha-2a in combination with ribavirin in treatment of eldly patients with chronic hepatitis C

To study the clinical efficacy of PEG-Interferon alpha-2a combined with ribavirin in eldly chronic hepatitis. Forty patients with chronic hepatitis C were divided into treatment group and comparative group. The twenty eldly patients of treatment group receive peg-interferon alpha-2a 135-180 microg subcutaneous injection every week combined with ribavirin 600-1000 mg/d for 48 weeks, and twenty adult patients of control group receive peg-interferon 135-180 microg subcutaneous injection every week combined with ribavirin 800-1200 mg/d for 48 weeks. The rapid virological response (RVR) rate, early virological response (EVR) rate, end of treatment virological response (ETVR) rate, sustained virological response (SVR) rate, nonresponder rate, relapse rate and the side reaction was assessed, then to compare the differences between the two groups. The RVR rate, EVR rate, ETVR rate, SVR rate, nonresponder rate, relapse rate was 60%, 70%, 75%, 60%, 10%, 10% respectively, accordingly the rate in control group was 75%, 80%, 85%, 75%, 5%, 10%. The difference between the two group were not statistically significant (P > 0.05). Compared with the control group, the rate of neutropenia was higher in treatment group (P < 0.05). There was no difference between the two groups in influenza-like side effect, anemia, thrombocytopenia and gastrointestinal side reaction. The eldly patients with Chronic Hepatitis C using general dose peg-IFNalpha-2a combined with lower dose ribavirin can still obtain the similar efficiency and excellent tolerance when the basic diseases such as hypertension, diabetes and side effects were treated successfully.

Treatment of hepatitis C in HCV mono-infected and in HIV-HCV co-infected patients: an open-labelled comparison study

Treatment of chronic HCV infection has become a priority in HIV+ patients, given the faster progression to end-stage liver disease. The primary endpoint of this study was to evaluate and compare antiviral efficacy of Peginterferon alpha 2a plus ribavirin in HIV-HCV co-infected and HCV mono-infected patients, and to examine whether 6 months of therapy would have the same efficacy in HIV patients with favourable genotypes 2 and 3 as in mono-infected patients, to minimise HCV-therapy-related toxicities. Secondary endpoints were to evaluate predictors of sustained virological response (SVR) and frequency of side-effects. Patients with genotypes 1 and 4 were treated for 48 weeks with Pegasys 180 microg/week plus Copegus 1000-1200 mg/day according to body weight; patients with genotypes 2 and 3 for 24 weeks with Pegasys 180 microg/week plus Copegus 800 mg/day. 132 patients were enrolled in the study: 85 HCV mono-infected (38: genotypes 1 and 4; 47: genotypes 2 and 3), 47 HIV-HCV co-infected patients (23: genotypes 1 and 4; 24: genotypes 2 and 3). In an intention-to-treat analysis, SVR for genotypes 1 and 4 was observed in 58% of HCV mono-infected and in 13% of HIV-HCV co-infected patients (P = 0.001). For genotypes 2 and 3, SVR was observed in 70% of HCV mono-infected and in 67% of HIV-HCV co-infected patients (P = 0.973). Undetectable HCV-RNA at week 4 had a positive predictive value for SVR for mono-infected patients with genotypes 1 and 4 of 0.78 (95% CI: 0.54-0.93) and of 0.81 (95% CI: 0.64-0.92) for genotypes 2 and 3. For co-infected patients with genotypes 2 and 3, the positive predictive value of SVR of undetectable HCV-RNA at week 4 was 0.76 (95%CI, 0.50-0.93). Study not completed by 22 patients (36%): genotypes 1 and 4 and by 12 patients (17%): genotypes 2 and 3. Genotypes 2 or 3 predict the likelihood of SVR in HCV mono-infected and in HIV-HCV co-infected patients. A 6-month treatment with Peginterferon alpha 2a plus ribavirin has the same efficacy in HIV-HCV co-infected patients with genotypes 2 and 3 as in mono-infected patients. HCV-RNA negativity at 4 weeks has a positive predictive value for SVR. Aggressive treatment of adverse effects to avoid dose reduction, consent withdrawal or drop-out is crucial to increase the rate of SVR, especially when duration of treatment is 48 weeks. Sixty-one percent of HIV-HCV co-infected patients with genotypes 1 and 4 did not complete the study against 4% with genotypes 2 and 3.

Peginterferon α-2a and ribavirin treatment of patients with haemophilia and hepatitis C virus infection: a single-centre study of 367 cases

Chronic hepatitis C virus infection (HCV) is a major comorbidity in patients with haemophilia. Peginterferon alpha and ribavirin is current standard anti-HCV therapy but there is little information about safety and efficacy of peginterferon alpha-2a and ribavirin combination therapy in these patients. In an open-label single-treatment arm cohort study, 367 haemophilia patients seronegative for hepatitis B and human immunodeficiency virus markers and chronically infected with HCV (HCV RNA>50 IU/ml for at least 6 months) received 180 microg of Pegasys and 800-1200 mg of ribavirin according to body weight. Genotypes 1 and 4, mixed and untypable infections were treated for 48 weeks, while genotypes 2 and 3 were treated for 24 weeks. The efficacy of therapy was expressed as sustained virological response (SVR). Two hundred and twenty-five subjects [61%, 95% confidence interval (CI) 56-66] achieved SVR, 66 patients relapsed and 30 subjects did not respond and nine patients developed breakthrough during treatment. In a multivariate logistic regression model, age<24 odds ratio (OR)=1.8 (95% CI 1.1-3.1), genotype non-1 OR=1.8 (95% CI 1.1-3.2), BMI<25 OR=2.1 (95% CI 1.3-3.3) and HCV RNA<600 000 IU/ml OR=1.7 (95% CI 1.1-3.2) were independent predictors of SVR. Eight patients discontinued the treatment because of persistent neutropaenia and 22 subjects were dropped out because of intractable side effects. Furthermore, two patients died during treatment and five were lost to follow-up after treatment cessation. Peginterferon alpha-2a in combination with weight-based ribavirin has SVR rate of 51% for genotype 1 and 71% for genotype non-1 infections in haemophilia patients. Age<24, BMI<25, viral load<600 000 IU/ml and genotype non-1 are the major determinants of SVR achievement in these patients.

Pegylated Interferon α -2a With or Without Ribavirin in HCV/HIV Coinfection: Partially Blinded, Randomized Multicenter Trial

We evaluated the safety and efficacy of peginterferon alpha-2a (pegIFNalpha-2a), with or without ribavirin, in 154 HCV/HIV coinfected patients. All received pegIFNalpha-2a (180 microg/week) for 12 weeks, with those achieving an early virologic response (EVR) continued on monotherapy through week 48. Patients without an EVR were randomized at week 14 to also receive ribavirin (800 mg/day) or placebo through week 48. Patients with detectable HCV RNA at week 24 were discontinued. An EVR occurred in 59 of 154 patients on monotherapy, and a sustained virologic response (SVR) occurred in 19 of 55 of those achieving an EVR and continuing monotherapy through week 48. One week 12 nonresponder receiving pegIFNalpha-2a plus ribavirin, and none receiving pegIFNalpha-2a plus placebo, achieved a SVR. Discontinuations for adverse events occurred in 10 of 154 patients before, and 16 of 131 after, week 14. HIV RNA and CD4 counts did not change significantly during treatment. PegIFNalpha-2a was therefore at least as effective as standard interferon and ribavirin combination therapy and was well tolerated, without a negative impact on HIV parameters.

Pegylated interferons for chronic hepatitis B

Conventional interferon therapy has been used for the treatment of chronic hepatitis B (CHB) for many decades. However, the use of interferon has been limited by its short half-life and high incidence of dose-related side effects. A meta-analysis investigating the short- and long-term consequences of interferon therapy showed that, whilst interferon therapy was beneficial in the short term, resulting in normalization of alanine aminotransferase (ALT) levels, loss of HBeAg, ‘e’ seroconversion and suppression of hepatitis B virus (HBV) DNA, the long-term benefits were less substantial. Pegylation of interferon (peginterferon alpha-2a [40 kDa]) led to improved pharmacokinetic and pharmacodynamic profiles, which translated to superior efficacy compared with conventional, nonpegylated interferon, in the treatment of chronic hepatitis C. A phase II study investigated the safety and efficacy of peginterferon alpha-2a (40 kDa) in the treatment of chronic hepatitis B. The results demonstrated a rapid and dramatic reduction in HBV DNA levels, HBeAg clearance and normalization of ALT with peginterferon alpha-2a (40 kDa) compared with conventional interferon. Furthermore, peginterferon alpha-2a (40 kDa) conferred a notably improved treatment response in patients with ‘difficult-to-treat’ hepatitis B infection. In conclusion, peginterferon alpha-2a (40 kDa) is a promising emerging therapy for CHB.