Peginterferon Alfa-2a In Patients Research Articles

Feasibility, tolerability, and first experience of intracystic treatment with peginterferon alfa-2a in patients with cystic craniopharyngioma.

Children with craniopharyngiomas (CPs) typically suffer from a life-long chronic disease. The younger the child, the more vulnerable the maturing brain is to invasive therapies such as surgery or radiotherapy. Therefore, treatment modalities facilitating avoidance or delay of invasive therapies are beneficial for these patients. In the last decade, intracystic injection of interferon alfa-2a or alfa-2b evolved as a treatment of choice based on efficacy and minor toxicity. However, the drug is no longer available internationally. After an extensive pharmacological review, peginterferon alfa-2a was identified as the agent with closest similarity. A retrospective case series is described, including five patients treated with intracystic peginterferon alfa-2a for cystic CP according to an innovative care protocol. After initial CP cyst aspiration, peginterferon alfa-2a was injected once per week via an Ommaya reservoir for 6 weeks followed by response assessment with MRI. Patients' age ranged from 4 to 54 years (four patients <12 years, one adult patient). Intracystic therapy with peginterferon alfa-2a was tolerated well by all five individuals without any major toxicities and resulted in cyst shrinkage in all of the five patients. The importance of a permeability study prior to commencing intracystic therapy became apparent in one patient who suffered from cyst leakage. Intracystic treatment with peginterferon alfa-2a was found to be a tolerable and efficacious treatment modality in patients with cystic CP. This experience warrants further research with a larger number of patients with measurement of long-term efficacy and safety outcomes.

AS072 - 48 weeks of high dose (10 mg) bulevirtide as monotherapy or with peginterferon alfa-2a in patients with chronic HBV/HDV co-infection

AS072 - 48 weeks of high dose (10 mg) bulevirtide as monotherapy or with peginterferon alfa-2a in patients with chronic HBV/HDV co-infection

Final analysis of the international observational S-Collate study of peginterferon alfa-2a in patients with chronic hepatitis B.

Background and aimsSustained off-treatment immune control is achievable in a proportion of patients with chronic hepatitis B treated with peginterferon alfa-2a. We evaluated on-treatment predictors of hepatitis B surface antigen (HBsAg) clearance 3 years after peginterferon alfa-2a treatment and determined the incidence of hepatocellular carcinoma.MethodsA prospective, international, multicenter, observational study in patients with chronic hepatitis B who have been prescribed peginterferon alfa-2a (40KD) in a real-world setting. The primary endpoint was HBsAg clearance after 3 years’ follow-up.ResultsThe modified intention-to-treat population comprised 844 hepatitis B e antigen (HBeAg)-positive patients (540 [64%] completed 3 years’ follow-up), and 872 HBeAg-negative patients (614 [70%] completed 3 years’ follow-up). At 3 years’ follow-up, HBsAg clearance rates in HBeAg-positive and HBeAg-negative populations, respectively, were 2% (16/844) and 5% (41/872) in the modified intention-to-treat population and 5% [16/328] and 10% [41/394] in those with available data. In HBeAg-positive patients with data, Week 12 HBsAg levels <1500, 1500–20,000, and >20,000 IU/mL were associated with HBsAg clearance rates at 3 years’ follow-up of 11%, 1%, and 5%, respectively (Week 24 predictability was similar). In HBeAg-negative patients with available data, a ≥10% decline vs a <10% decline in HBsAg at Week 12 was associated with HBsAg clearance rates of 16% vs 4%. Hepatocellular carcinoma incidence was lower than REACH-B (Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B) model predictions.ConclusionsSustained off-treatment immune control is achieved with peginterferon alfa-2a in a real-world setting. HBsAg clearance 3 years after completion of peginterferon alfa-2a can be predicted on the basis of on-treatment HBsAg kinetics.

Extended duration of treatment with peginterferon alfa-2a in patients with chronic hepatitis B, HBeAg-negative and E genotype: A retrospective analysis.

An alternative approach in the treatment of chronic hepatitis B (CHB) with pegylated (PEG)-interferon (IFN) is the prolonged course to 96 weeks of therapy, with higher sustained response (SR) than patients treated for 48 weeks. This result was confirmed in patients with CHB and D genotype, while no data are currently available about the prolonged course of PEG-IFN in E genotype. This retrospective analysis reported the role of different treatment duration of PEG-IFN on the SR in patients affected by CHB and E genotype. A total of 86 subjects with CHB and E genotype were considered in this analysis; different treatment durations were: 48 weeks (control group, 41 patients), 72 weeks (25 patients), and 96 weeks (19 patients). Treatment effectiveness was evaluated with sustained response (SR) and serological response. SR was significantly higher in patients who underwent PEG-IFN for 96 weeks in comparison to 48 weeks: 14.6% versus 26.3% (P = 0.016). HBsAg loss rate was 5.3% in patients treated for 96 weeks and 2.4% in the control group. In the multivariate analysis only the 72 and 96 weeks of therapy (OR 2.335, 95% CI 1.550-4.578; P = 0.020 and (OR 3.890, 95% CI 1.991-10.961; P = 0003) were predictive of SR. The extended duration of PEG-IFN course in patients with CHB and genotype E is a promising approach to increase the SR and HBsAg clearance.

An easy-to-use baseline scoring system to predict response to peginterferon alfa-2a in patients with chronic hepatitis B in resource-limited settings

Approximately one-third of patients have durable responses after finite (48-week) treatment with peginterferon alfa-2a. The ability to identify patients likely to respond would be particularly useful in resource-limited settings. Data from 1,363 peginterferon alfa-2a recipients (955 hepatitis B 'e' antigen [HBeAg]-positive and 408 -negative) in six studies were analysed. Baseline scoring systems were developed using generalized additive models and multiple logistic regression analysis to predict virological response (VR; HBV DNA <2,000 IU/ml), alone or combined with alanine aminotransferase (ALT) normalization (CR) at 24 weeks post-treatment. Based on the final models, points were assigned for age ≥45 (0) or <45 years (1); male (0) or female (1); hepatitis B surface antigen (HBsAg) >25,000 (0), >7,500-≤25,000 (1), >1,250-≤7,500 (2) or ≤1,250 IU/ml (4); HBV DNA >5 (0) or ≤5 log10 IU/ml (2) and ALT ratio >1-7 (0) or either ≤1 or >7 (1). Higher total scores (range 0-9) indicate higher likelihood of response. VR and CR rates were 28.5% (388/1,363) and 24.4% (332/1,363), respectively, and increased with increasing score: score 0-1 (n=257), VR 14.8%, CR 12.8%; score 2-3 (n=711), VR 23.1%, CR 20.1%; score ≥4 (n=395), VR 47.1%, CR 39.5%. An easy-to-use baseline scoring system for use in settings where HBeAg status and HBV genotypes are unavailable would allow clinicians to identify patients with a low or high chance of achieving a durable post-treatment response to peginterferon alfa-2a. The tool can be used to inform treatment decisions in resource-limited settings.

EFFICACY AND SAFETY OF THE COMBINATION OF RIBAVIRIN AND PEGYLATED INTERFERON ALFA-2A IN PATIENTS WITH CHRONIC HEPATITIS C: THE RESULTS OF TWO MULTICENTER, PROSPECTIVE, OPEN, NON-COMPARATIVE CLINICAL TRIALS

Aim. Study of efficacy and safety of ribavirin in combination to pegylated interferon α-2a (PegIFN- α-2a) within combined mode of treatment of patients with chronic hepatitis C (CHC) including patients with compensated cirrhosis and and HIV coinfection were conducted. Material and methods. Two open prospective multicenter, non-comparative clinical trials ML16709 NCT00922779 and ML27851 «Standart» (NCT01609049) were conducted. 6661 and 1496 patients with CHC were included accordingly. All were administrated combined therapy: ribavirin and PegIFN- α-2a. Patients with HCV genotype 1 received prescribing treatment for at least 12 but not more than 48 weeks, patients with HCV genotypes 2 and 3 – for at least 12 but not more than 24 weeks. The efficacy analysis included determining the frequency of achieving a rapid virologic response (BVO), an early virologic response (RVO), a virologic response at the end of therapy, and a sustained virologic response (SVR). The safety endpoints were assessed on data of all adverse events (AEs), serious adverse events (SNP), and clinical laboratory findings. Results. At 24 weeks SVR frequency was 43.4% in the subgroup of patients with HCV genotype 1 in the ML16709 study and 72,0% in the ML27851 study; 58,9% and 89,3% in the subgroup of patients with HCV genotypes 2 and 3 accordingly. In the ML27851 study proportion of patients with BVO was 46,8% in patients with HCV genotype 1 and 86,0% in patients with a different HCV genotype. RVO frequency was 37,4% in the subgroup of patients with HCV genotype 1 in the ML16709 study and 90,1% in the ML27851 study; 79,7% and 97,4% in a subgroup of patients with HCV genotypes 2 and 3 accordingly. The proportion of patients with virologic response at the end of therapy was 44,6% in the ML16709 study and 86.7% in the ML27851 study; in a subgroup of patients with genotypes 2 and 3, 73.8% and 97.6%, accordingly. In the ML16709 study 5887 AEs were registered, including 5812 (99%) of non-serious AEs and 75 serious AEs. In the ML27851 study 2557 non-serious AEs occurred in 822 (54.95%) patients. 49 serious AEs were registered in 39 patients (2.6%). Conclusion. The results of studies ML16709 and ML27851 confirm the efficacy and safety of treatment with ribavirin plus peginterferon alfa-2a in patients with chronic hepatitis C. The registered AEs profile is representative of pegylated interferons and ribavirin combination.

FRI-138 - A Genotype-Specific Baseline Score to Predict Response at 48 Weeks Post-Treatment to Peginterferon Alfa-2a in Patients with HBeAg-Negative Chronic Hepatitis B

FRI-138 - A Genotype-Specific Baseline Score to Predict Response at 48 Weeks Post-Treatment to Peginterferon Alfa-2a in Patients with HBeAg-Negative Chronic Hepatitis B

FRI-139 - An Easy-to-Use Baseline Score to Predict Response to Peginterferon Alfa-2a in Patients with Chronic Hepatitis B in Resource-Limited Settings

FRI-139 - An Easy-to-Use Baseline Score to Predict Response to Peginterferon Alfa-2a in Patients with Chronic Hepatitis B in Resource-Limited Settings

The effectiveness and safety of Peginterferon alfa-2a in patients with chronic hepatitis C on haemodialysis

BackgroundHepatitis C (HCV) virus infection is the most common cause of liver disease in patients on haemodialysis (HD). It's a very serious and difficult health problem in these patients because...

P68 PACIFIC: a phase III, randomised, multicentre, dose escalation, efficacy and safety study examining the effects of treatment with peginterferon alfa-2a in patients with Child's A or B cirrhosis in chronic hepatitis C virus infection

IntroductionTrials have found conflicting results about the efficacy of pegylated interferon α (PIFN), with or without pretreatment including ribavirin, as an antifibrotic agent in patients with established cirrhosis due to...

Silencing of USP18 Potentiates the Antiviral Activity of Interferon Against Hepatitis C Virus Infection

Modulation of the host innate immune response is an attractive means of inhibiting hepatitis C virus (HCV) replication. Having previously determined that expression of the interferon-sensitive gene (ISG)15 protease USP18 is increased in the liver biopsy specimens of patients who do not respond to interferon (IFN)-alfa therapy, we hypothesized that USP18 might hinder the ability of IFN to inhibit HCV replication. The role of USP18 in IFN antiviral activity was examined using an in vitro model of HCV replication that reproduces the full viral life cycle. USP18 was silenced specifically using small inhibitory RNAs (siRNAs), and the dose response of HCV replication and infectious virus production to IFN-alfa was measured. The siRNA knockdown of USP18 in human cells consistently potentiated the ability of IFN to inhibit HCV-RNA replication and infectious virus particle production by a factor of 1-2 log(10). USP18 knockdown also resulted in a number of cellular changes consistent with increased sensitivity to IFN. Decreasing USP18 expression led to increased cellular protein ISGylation in response to exogenous IFN-alfa, prolonged tyrosine phosphorylation of signal transducer and activation of transcription (STAT1), and a general enhancement of IFN-stimulated gene expression. These data suggest that USP18 modulates the anti-HCV type I IFN response, and is a possible therapeutic target for the treatment of HCV infection.

A randomised trial to compare the pharmacokinetic, pharmacodynamic, and antiviral effects of peginterferon alfa-2b and peginterferon alfa-2a in patients with chronic hepatitis C (COMPARE)

To compare the pharmacokinetics, pharmacodynamics, and antiviral activity of peginterferon alfa-2b and peginterferon alfa-2a in patients with chronic hepatitis C virus genotype 1. Thirty-six patients were randomised to peginterferon alfa-2b (1.5 microg/kg/week) or peginterferon alfa-2a (180 microg/week) for 4 weeks, then in combination with ribavirin (13 mg/kg/day) for a further 4 weeks. The pharmacokinetic profile of both peginterferons, mRNA expression of a selected group of interferon-induced gene transcripts, and serum HCV-RNA levels were assessed. Patients receiving peginterferon alfa-2b had significantly greater up-regulation of interferon-alfa response genes compared with those receiving peginterferon alfa-2a. Correspondingly, patients treated with peginterferon alfa-2b also had a significantly greater log10 maximum and log10 time-weighted average decrease in serum HCV-RNA. A greater proportion of peginterferon alfa-2b patients achieved a > or = 2.0 log10 reduction in serum HCV-RNA levels by week 8 (72% vs 44% of peginterferon alfa-2a patients, P = 0.09). There was an approximately 16-fold greater exposure to peginterferon in the serum of patients treated with peginterferon alfa-2a. These findings suggest that the biological activity, measured by early interferon-induced gene transcripts and early antiviral responsiveness, may have been greater in patients treated with peginterferon alfa-2b despite their lower exposure to the drug compared with patients treated with peginterferon alfa-2a.

Peginterferon alfa-2a for hepatitis C after liver transplantation: Two randomized, controlled trials

There is currently no effective treatment for recurrent hepatitis C after orthotopic liver transplantation (OLT). We therefore performed two randomized, controlled trials--a prophylaxis trial and a treatment trial--to evaluate the safety and efficacy of peginterferon alfa-2a in patients who had undergone OLT. The prophylaxis trial enrolled 54 patients within 3 weeks after OLT, and the treatment trial enrolled 67 patients 6 to 60 months after OLT. In each trial, patients were randomized to treatment with once weekly injections of 180 microg peginterferon alfa-2a or no antiviral treatment for 48 weeks and were followed up for 24 weeks thereafter. Peginterferon alfa-2a treated patients had significantly lower hepatitis C virus RNA levels and more favorable changes in hepatic histological features compared with untreated controls. However, only 2 treated patients in the prophylaxis trial (8%) and 3 in the treatment trial (12%) achieved a sustained virological response. In the prophylaxis trial, 8 patients (31%) in the peginterferon alfa-2a group and 9 (32%) in the untreated group were withdrawn prematurely; whereas in the treatment trial, 10 patients (30%) in the peginterferon alfa-2a group and 6 (19%) in the untreated group were withdrawn prematurely. The incidence of acute rejection was similar in the treated and untreated groups in both the prophylaxis (12% vs. 21%; P = .5) and treatment (12% vs. 0%; P = .1) trials. In conclusion, peginterferon alfa-2a treatment for 48 weeks is safe and tolerable and offers some efficacy in the post-OLT setting. Randomized controlled studies are needed to establish the efficacy of pegylated interferon and ribavirin in patients who have undergone OLT.