Peginterferon Alfa-2b Research Articles

Long-term Combined Therapy with Very-low-dose Peginterferon and Ursodeoxycholic Acid Decreased the Spleen Size in a Patient with Hepatitis C Virus-related Cirrhosis

A 42-year-old woman with hepatitis C virus-related cirrhosis underwent peginterferon alpha-2b therapy combined with ribavirin but could not achieve a sustained viral response. Following discontinuation of this combined therapy, the patient's serum transaminase levels suddenly became elevated. Therefore, the administration of very-low-dose peginterferon alpha-2a with ursodeoxycholic acid was introduced. Thereafter, the patient's serum transaminase levels gradually improved. Four years later, enhanced computed tomography showed shrinkage of the spleen and enlargement of the liver. Long-term combined therapy with very-low-dose peginterferon and ursodeoxycholic acid may be effective not only in preventing disease progression, but also in improving portal hypertension in patients hepatitis C virus-related cirrhosis.

Resultados del tratamiento de la hepatitis crónica por virus C en un hospital público, en Chile

Chronic hepatitis C is an important health problem in Chile. In 2005, the Ministry of Health started a pilot treatment program with peg interferon and ribavirin, to be developed in public hospitals all over the country. To report the results of hepatitis C treatment obtained at our institution. Between 2005 and 2009, 63 patients were referred for treatment. In all, the viral load and genotype were determined. Peg interferon alpha-2a or alpha-2b plus ribavirin were used for therapy for up to 48 weeks in genotypes (G) 1 or 4 or 24 weeks in genotypes 2 or 3. If at the end of treatment, viral load measured by polymerase chain reaction (PCR) was negative, it was repeated 6 months later. A negative viral load at that time was considered a sustained viral response (SVR). Among the 51 patients who started treatment, 42 (80.4%) were G1,1 was G2,1 was G4 and 7 were G3. A SVR was reached in 51.1% of G 1 and 4 and in 87.5% in G 3 and 2. In a univariate analysis, the variables significantly associated with a positive viral response were the degree of fibrosis and body mass index. These results are similar to those obtained in other international series, demonstrating that Hispanic ethnicity does not influence the response to treatment. Our good results could be explained by the excellent compliance of the patients to the treatment. A higher degree of fibrosis and a higher BMI were associated with a poor response.

Direct-acting antiviral therapies for hepatitis C genotype 1 infection: a multiple treatment comparison meta-analysis

Background: New direct-acting antiviral agents for hepatitis C genotype 1 infection, boceprevir and telaprevir, offer enhanced sustained virologic response (SVR) among both treatment-naïve and treatment-experienced patients.Aim: To determine the relative efficacy of the new direct-acting antiviral agents by applying a multiple treatment comparison meta-analysis.Design: We included published Phase II and III randomized controlled trials evaluating head-to-head comparisons between boceprevir, telaprevir, peg-interferon alpha-2a with ribavirin and peg-interferon alpha-2b with ribavirin in hepatitis C genotype 1 patients. We applied Bayesian multiple treatment comparison meta-analysis.Results: We included data from four boceprevir, three telaprevir and six peg-interferon alpha-2a plus ribavirin vs. peg-interferon alpha-2b plus ribavirin randomized controlled trials. Both boceprevir and telaprevir offer statistically superior outcomes for SVR, relapse and discontinuation due to adverse events than either peg-interferons among both treatment-naïve and treatment-experienced patients. Among treatment-naïve patients, clinical outcomes were similar for boceprevir and telaprevir, for SVR [odds ratio (OR) 0.90, 95% credible interval (95% CrI) 0.41–1.91] and for relapse (OR 1.09, 95% CrI 0.19–4.84). Similarly, among treatment-experienced patients, clinical outcomes were similar for boceprevir and telaprevir and for SVR (OR 1.45, 95% CrI 0.70–3.08) and for relapse (OR 0.35, 95% CrI 0.13–1.02). For treatment-naïve patients receiving standard-duration therapy, telaprevir yielded lower rates of anemia and neutropenia, but higher rates of rash and pruritus. For treatment-experience patients, all adverse event rates were higher with telaprevir.Discussion: Boceprevir and telaprevir exhibit similar effects among hepatitis C genotype 1 treatment-naïve and treatment-experienced patients.

Improved inflammatory activity with peginterferon alfa-2b maintenance therapy in non-cirrhotic prior non-responders: A randomized study

Therapeutic options for patients failing hepatitis C retreatment are limited. EPIC(3) included a prospective trial assessing long-term peginterferon alfa-2b (PegIFNα-2b) maintenance therapy in patients with METAVIR fibrosis scores (MFS) of F2 or F3 who previously failed hepatitis C retreatment. Patients with F2/F3 MFS who failed retreatment were randomized to PegIFNα-2b (0.5 μg/kg/week, n=270) or observation (n=270) for 36 months. Blinded liver biopsies obtained before retreatment and after maintenance therapy were evaluated using MFS and activity scores, and confirmatory testing was performed using FibroTest and ActiTest. In total, 348 patients had paired biopsies: 192 patients had missing post-treatment biopsies and were considered as having no change in fibrosis/activity scores. In total, 16% of patients receiving PegIFNα-2b and 11% of observation patients had improvement in MFS (p=0.32). More PegIFNα-2b than observation patients had improvement in activity score (20% vs. 9%; p <0.001). Among patients treated for >2.5 years, improvement in MFS or activity score was more common with PegIFNα-2b than observation (21% vs. 14%, p=0.08 and 26% vs. 10%, p <0.001). FibroTest and ActiTest evaluations indicated significant benefit associated with PegIFNα-2b in terms of reduced fibrosis progression and improved activity score. The safety profile of PegIFNα-2b was similar to previous studies. PegIFNα-2b did not significantly improve MFS estimated by biopsy compared with observation; however, activity scores were significantly improved and MFS trended toward increased improvement with treatment durations >2.5 years. Both FibroTest and ActiTest were significantly improved during maintenance therapy.

PGI1 The Effectiveness and Tolerability of Combined Treatment With Peginterferon Alpha-2a or Alpha-2b and Ribavirin in the Treatment of Patients With Chronic Hepatitis C: Results Based on the Nationwide Hepatitis Registry in Japan

PGI1 The Effectiveness and Tolerability of Combined Treatment With Peginterferon Alpha-2a or Alpha-2b and Ribavirin in the Treatment of Patients With Chronic Hepatitis C: Results Based on the Nationwide Hepatitis Registry in Japan

Is Combination Therapy Interferon and Ribavirin in Patients with Chronic Hepatitis C Infection Toxic for Eyes?

Many side effects of combination therapy using pegylated interferon (IFN) and ribavirin for treatment of chronic hepatitis C virus (HCV) infection have been well described. Ocular complications are fairly common. Diabetes mellitus (DM) and systemic hypertension are possible suggested risk factors for development of these complications. To determine the frequency of retinopathy and its risk factors in patients treated with combined pegylated IFN and ribavirin for chronic hepatitis C infection. Eligible 98 patients for HCV treatment with pegylated IFN a-2a, a-2b, and ribavirin between October 2011 and March 2012 were included. All patients underwent a baseline full ophthalmological examination, and any visual complaints during treatment prompted a repeat eye examination. Out of the eligible 98 patients, 48 (48.78%) patients received pegylated IFN alpha-2a, and the other 50 (51.21%) patients were treated with pegylated IFN alpha-2b. Out of 98 patients, 21 (21.42%) had diabetes; 19 (19.38%) patients had hypertension and 16 (16.32%) patients had both diabetes; and hypertension. Only 8 patients (8.16%) had documented retinopathy [2 had DM; one had hypertension; 4 had both hypertension and diabetes; and one patient without DM or hypertension]. Univariate logistic regression analysis revealed that diabetic, hypertensive patients are at increased risk for development of IFN-associated retinopathy (IAR) (P=0.007, Odds ratio=6.5, 95% confidence interval=1.56-27. Retinopathy in chronic HCV-infected patients undergoing treatment with combination of pegylated IFN-alpha and ribavirin therapy appears to be relatively low, and treatment cessation is rarely needed. Diabetic, hypertensive patients are at increased risk for IAR and are recommended to be ophthalmologically followed-up.

Efficacy of pegylated interferon alpha-2b and ribavirin treatment on the risk of hepatocellular carcinoma in patients with chronic hepatitis C: A prospective, multicenter study

The effects of pegylated interferon (PegIFN) α and ribavirin (RBV) treatment of chronic hepatitis C on the incidence of hepatocellular carcinoma (HCC) have not been well established. This study investigated the impact of treatment outcome on the development of HCC by chronic hepatitis C patients treated with PegIFNα2b and RBV. This large-scale, prospective, multicenter study consisted of 1013 Japanese chronic hepatitis C patients with no history of HCC (non-cirrhosis, n=863 and cirrhosis, n=150). All patients were treated with PegIFNα2b and RBV and the follow-up period started at the end of the antiviral treatment (median observation period of 3.6 years). The cumulative incidence rate of HCC was estimated using the Kaplan-Meier method, according to treatment outcome. Forty-seven patients (4.6%) developed HCC during the observation period. In the non-cirrhosis group, the 5-year cumulative incidence rates of HCC for the sustained virological response (SVR) (1.7%) and transient virological response (3.2%) (TVR: defined as relapse or breakthrough) groups were significantly lower than those of the non-virological response (NVR) group (7.6%) (p=0.003 and p=0.03, respectively). A significantly low rate of incidence of HCC by TVR patients in comparison with NVR patients was found for patients aged 60 years and over, but not for those under 60 years of age. In the cirrhosis group, the 5-year cumulative incidence rates of HCC for the SVR (18.9%) and TVR groups (20.8%) were also significantly lower than those of the NVR group (39.4%) (p=0.03 and p=0.04, respectively). SVR and complete viral suppression during treatment with relapse (TVR) were associated with a lower risk of HCC development when compared with NVR.

Boceprevir With Peginterferon Alfa-2a–Ribavirin Is Effective for Previously Treated Chronic Hepatitis C Genotype 1 Infection

The addition of boceprevir to therapy with peginterferon alfa-2b and ribavirin results in significantly higher rates of sustained virologic response (SVR) in previously treated patients with chronic hepatitis C virus (HCV) genotype-1 infection, compared with peginterferon alfa-2b and ribavirin alone. We assessed SVR with boceprevir plus peginterferon alfa-2a-ribavirin (PEG2a/R) in patients with identical study entry criteria. In a double-blind, placebo-controlled trial, 201 patients with HCV genotype-1 who had relapsed or not responded to previous therapy were assigned to groups (1:2) and given a 4-week lead-in phase of PEG2a/R, followed by placebo plus PEG2a/R for 44 weeks (PEG2a/R) or boceprevir plus PEG2a/R for 44 weeks (BOC/PEG2a/R). The primary end point was SVR 24 weeks after therapy ended. The addition of boceprevir after 4 weeks of lead-in therapy with PEG2a/R significantly increased the rate of SVR from 21% in the PEG2a/R group to 64% in the BOC/PEG2a/R group (P < .0001). Among patients with poor response to interferon therapy (<1-log(10) decline in HCV RNA at week 4), 39% in the BOC/PEG2a/R group had SVRs, compared with none of the patients in the PEG2a/R group. Among patients with good response to interferon (≥1-log(10) decline), 71% in the BOC/PEG2a/R group had SVRs, compared with 25% in the PEG2a/R group. A ≥1-log(10) decline in HCV RNA at treatment week 4 was the strongest independent predictor of SVR, exceeding that of IL-28B genotype. Among 8 patients who began the study with HCV amino acid variants associated with boceprevir resistance, 3 (38%) achieved SVRs. Fifty percent of patients in the BOC/PEG2a/R group developed anemia (hemoglobin <10.0 g/dL), compared with 27% in the PEG2a/R group; 43% vs 21%, respectively, developed neutropenia (neutrophil count <750/mm(3)). The addition of boceprevir after 4 weeks of lead-in therapy with PEG2a/R caused significantly higher rates of SVR in previously treated patients with chronic HCV genotype-1 infection, compared with patients given only PEG2a/R. ClinicalTrials.gov Identifier: NCT00845065.

How Much of a Good Thing? What Duration for Interferon Alfa-2b Adjuvant Therapy?

How Much of a Good Thing? What Duration for Interferon Alfa-2b Adjuvant Therapy?

Long-Term Results of the Randomized Phase III Trial EORTC 18991 of Adjuvant Therapy With Pegylated Interferon Alfa-2b Versus Observation in Resected Stage III Melanoma

Adjuvant pegylated interferon alfa-2b (PEG-IFN-α-2b) was approved for treatment of resected stage III melanoma in 2011. Here, we present long-term follow-up results of this pivotal trial. In all, 1,256 patients with resected stage III melanoma were randomly assigned to observation (n = 629) or PEG-IFN-α-2b (n = 627) for an intended duration of 5 years. Stratification factors were microscopic (N1) versus macroscopic (N2) nodal involvement, number of positive nodes, ulceration and tumor thickness, sex, and center. Recurrence-free survival (RFS; primary end point), distant metastasis-free survival (DMFS), and overall survival (OS) were analyzed for the intent-to-treat population. At 7.6 years median follow-up, 384 recurrences or deaths had occurred with PEG-IFN-α-2b versus 406 in the observation group (hazard ratio [HR], 0.87; 95% CI, 0.76 to 1.00; P = .055); 7-year RFS rate was 39.1% versus 34.6%. There was no difference in OS (P = .57). In stage III-N1 ulcerated melanoma, RFS (HR, 0.72; 99% CI, 0.46 to 1.13; P = .06), DMFS (HR, 0.65; 99% CI, 0.41 to 1.04; P = .02), and OS (HR, 0.59; 99% CI, 0.35 to 0.97; P = .006) were prolonged with PEG-IFN-α-2b. PEG-IFN-α-2b was discontinued for toxicity in 37% of patients. Adjuvant PEG-IFN-α-2b for stage III melanoma had a positive impact on RFS, which was marginally significant and slightly diminished versus the benefit seen at prior follow-up (median, 3.8 years). No significant increase in DMFS or OS was noted in the overall population. Patients with ulcerated melanoma and lower disease burden had the greatest benefit.

Continuous versus intermittent treatment strategies during primary HIV-1 infection

The ANRS-112 INTERPRIM trial assessed whether fixed-cycles of antiretroviral treatment interruption (ART-STI) combined or not with pegylated interferon alpha-2b (peg-IFN) could lower viral load and achieve a healthier immune system in patients diagnosed during primary HIV-1-infection (PHI). Patients were randomized to receive either continuous ART (cART) during 72 weeks, or cART during 36 weeks followed by three ART-STIs, or the same ART-STIs associated with peg-IFN during the first 14 weeks and each interruption (ART-STI-IFN). Treatment was stopped at week 72. Final evaluation was based on plasma HIV-RNA level 6 months after the last treatment interruption. Eighty-seven percent of patients achieved undetectable HIV-RNA at week 32, with no deleterious impact of sequential treatment interruptions (STIs). Viral rebounds during interruptions were lower in the ART-STI-IFN than in the ART-STI group and during the second and third interruptions compared with the first one. However, HIV-RNA levels, CD4 T-cell counts and CD4 T/CD8 T ratios were similar between groups after the 6-month interruption, with a persistent effect on CD4 T cells and total cell-associated HIV-DNA levels. Predictive factors of virological outcome were HIV-RNA and HIV-DNA levels at PHI and HIV-DNA levels at treatment interruption. HIV-specific responses did not differ between strategies and were not associated with outcome. Forty-eight percent of patients experienced treatment resumption during long-term follow-up without difference between groups. When initiated during PHI, STIs associated or not with IFN did not result in a different outcome as compared to cART. All regimens showed a high response rate and a sustained immunological benefit after cessation.

U.S. Food and Drug Administration Approval: Peginterferon-alfa-2b for the Adjuvant Treatment of Patients with Melanoma

On March 29, 2011, the U.S. Food and Drug Administration approved peginterferon alfa-2b (PEG-IFN) (Sylatron™; Schering Corporation, Kenilworth, NJ) for the adjuvant treatment of melanoma patients with microscopic or gross nodal involvement following definitive surgical resection including complete lymphadenectomy. The approval was based on a single, open-label, multicenter trial enrolling 1,256 patients. After surgical resection, patients were randomized (1:1) to either PEG-IFN or observation for 5 years. PEG-IFN, 6 μg/kg per week, was administered s.c. for eight doses, followed by 3 μg/kg per week for up to 252 weeks. Stratification factors included microscopic or gross nodal involvement, number of positive nodes, Breslow thickness, ulceration, sex, and study center. Patients were assessed for recurrence by the investigators based on physical examination every 3 months for 2 years and every 6 months thereafter. The relapse-free survival (RFS) interval, the primary efficacy endpoint, was significantly longer in PEG-IFN-treated patients. The median RFS times were 34.8 months and 25.5 months, respectively. There was no statistically significant difference in the overall survival time. The most common (>60%) grade 1-4 adverse reactions were fatigue, increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST), pyrexia, headache, anorexia, myalgia, nausea, chills, and injection site reactions. The most common serious adverse reactions were fatigue, increased ALT and AST, and pyrexia. Thirty-three percent of patients receiving PEG-IFN discontinued treatment as a result of adverse reactions. Five deaths were reported within 30 days of the last treatment dose, two resulting from cardiovascular disease considered as possibly related to treatment.

Efeitos colaterais do tratamento da hepatite C no polo aplicador do ABC

To review and compare side effects of hepatitis C treatment with pegylated interferon and ribavirin at the CRIE of the Hospital Mário Covas (Santo André), São Paulo, Brazil, from February 23 to May 5, 2011. Cross-sectional study through questionnaire, with a non-probability sample comprised of 340 patients that had received at least one dose of the medication. Side effects presented were fatigue (82.9%), arthralgia and/or myalgia (76.8%), weight loss (71.8%), headache (67.6%), listlessness (65.9%), depression and/or irritability (64.4%), itching (60.6%), fever (59.1%), alopecia (51.5%), dry cough (34.1%), nausea (11.7%), inappetence (11.7%), and dizziness (7.9%). Up to 19 symptoms were reported during treatment. Only four patients (1.2%) did not present side effects. When comparing the types of interferon, it was observed that alpha-2b caused an average of 8.01 symptoms per patient, while alpha-2a was responsible for an average of 7.50 symptoms. Patients using interferon alpha-2b showed more fever, weight loss, headache, arthralgia and/or myalgia, fatigue, listlessness, depression and/or irritability, and dry cough than patients using alpha-2a, who had more alopecia and itching. The study shows a high morbidity related to the treatment, as only 1.2% of the patients showed no side effects. In the sample, the pegylated interferon alpha-2b was responsible for higher prevalence of fever and weight loss when compared to alpha-2a, and this was a statistically significant relation (p < 0.05).

The acute hepatic flare in a patient with chronic hepatitis C infection receiving pegylated interferon alpha 2b and ribavirin

The pegylated interferon alpha and ribavirin treatment is well established therapy for hepatitis C virus (HCV) infection. During the treatment alanine aminotransferase (ALT) flare may be observed rarely. A 51-year-old female receiving pegylated interferon and ribavirin therapy for HCV infection, complained nausea, vomiting in seventh week of the therapy, and her ALT level was detected over 20 times above the normal level. Hepatitis B surface antigen, anti-nuclear antibody, anti-mitochondrial antibody, anti-double stranded DNA antibody and anti-hepatitis A virus IgM antibody were negative, and thyroid stimulating hormone was normal. HCV RNA level was 424 IU/ml. PEG IFN and ribavirin therapy was interrupted for three weeks, after liver enzyme level was detected less than 100U/L, the treatment was resumed. The patient was followed up for 2 months, ALT flare was not observed. In conclusion, we present a rare case with ALT flare, while receiving pegylated interferon and ribavirin therapy for chronic HCV infection. J Microbiol Infect Dis 2012; 2(3): 122-124

Age-dependent rise in early Hemoglobin (Hb) decline contributes to a higher frequency of anemia in elder patients treated with peginterferon alfa-2b (Peg2b)/Ribavirin (RBV) for chronic HCV Genotype 1 (G1) infection

Age-dependent rise in early Hemoglobin (Hb) decline contributes to a higher frequency of anemia in elder patients treated with peginterferon alfa-2b (Peg2b)/Ribavirin (RBV) for chronic HCV Genotype 1 (G1) infection

Thyroid dysfunction induced by peginterferon alfa-2b (Peg-2b)/Ribavirin (RBV) is a favorable predictor of SVR in difficult-to-treat patients with HCV Genotype 1 (G1) infection

Thyroid dysfunction induced by peginterferon alfa-2b (Peg-2b)/Ribavirin (RBV) is a favorable predictor of SVR in difficult-to-treat patients with HCV Genotype 1 (G1) infection

Role of IL‐28B and inosine triphosphatase polymorphisms in efficacy and safety of Peg‐Interferon and ribavirin in chronic hepatitis C compensated cirrhosis with and without oesophageal varices

Genetic factors can influence the outcome of antiviral therapy in chronic hepatitis C (HCV). We evaluated the role of interleukin-28B single nucleotide polymorphisms (SNPs) and inosine triphosphatase (ITPA) gene variants in HCV cirrhosis treated with Peg-Interferon and ribavirin. A prospective cohort of 233 patients with compensated cirrhosis received 1-1.5 μg/kg/week of Peg-Interferon alpha-2b plus 1000-1200 mg/day of RBV for 48 weeks. A sustained virologic response (SVR) was achieved in 27% of patients. On multivariate logistic analysis, the absence of oesophageal varices (OR 3.64 CI 95% 1.27-10.44 P = 0.016), infection with genotype 2 or 3 (OR 4.06, CI 95% 1.08-15.26, P = 0.038), C/C alleles of rs12979860 SNP (OR 7.04, CI 95% 2.40-20.72, P < 0.001) and rapid virologic response (RVR) (OR 78.29, CI 95% 16.07-381.29, P < 0.001) were independently associated with SVR. Patients who experienced post-treatment relapse received lower total doses of Peg-Interferon (52.0 ± 15.8 μg/kg vs 65.7 ± 13.3 μg/kg, P < 0.001) and lower total dose of RBV (3829 ± 1210 mg vs 4709 ± 954 mg, P < 0.001) than patients who achieved an SVR. ITPA variants predictive of high ITPase activity were associated with reduction of haemoglobin ≥3 g/dL in the first 4 weeks (P < 0.001), and with reduction of haemoglobin <10 g/dL (P = 0.03) on treatment. In conclusion, combination therapy with Peg-Interferon and RBV in patients with HCV cirrhosis must be guided by virus genotype, severity of portal hypertension, favourable IL-28B polymorphisms and ITPA variants, and RVR on treatment.

Meta-analysis: mortality and serious adverse events of peginterferon plus ribavirin therapy for chronic hepatitis C

Pegylated interferon (PEG-IFN) plus ribavirin (RBV) therapy is the current standard of care for patients with chronic hepatitis C. Determining precisely the risk of serious adverse events (SAEs) and mortality from a single study is rather difficult because of the infrequency of such events. The aim of this systematic review was to assess the rates of SAEs and the mortality of PEG-IFN/RBV therapy in a pooled large sample, and to assess the relationship between SAEs and mortality rates and therapeutic characteristics. A literature search was conducted using MEDLINE, EMBASE, and the Cochrane Library to identify randomized controlled trials evaluating the efficacy and safety of PEG-IFN/RBV therapy. We calculated the crude mortality and SAE rates with 95% confidence intervals (CIs). Eighty studies with 153 treatment arms that included 27569 patients were enrolled (14401 patients treated with Peg-IFN alpha-2a/RBV and 13168 with Peg-IFN alpha-2b/RBV). All-cause and treatment-related deaths were observed in 50 (0.18%; 95% confidence interval [CI] 0.13-0.24%) and sixteen (0.058%; 95% CI 0.033-0.094%) patients, respectively. The crude SAE rate was 7.08% (95% CI 6.75-7.41%). Subgroup analysis revealed higher SAE rates in patients receiving PEG-IFN alpha-2a than in those with PEG-IFN alpha-2b (7.45 vs. 6.74%), and higher SAE rates with higher doses than with the lower doses in PEG-IFN-2a and 2b (11.94 vs. 6.99%, 7.10 vs. 5.05%, respectively), and with extended duration (> 48 weeks) than with standard duration (48 weeks) (15.5 vs. 6.67%) in PEG-IFN alpha-2a. The mortality rate during PEG-IFN/RBV therapy was acceptably low, but the rate of SAEs was not negligible in a treatment for a benign disease, and the rate was affected by treatment regimens.

Clinical utility of the ARCHITECT HCV Ag assay for early treatment monitoring in patients with chronic hepatitis C genotype 1 infection

BackgroundVirologic response-monitoring is essential for determining therapy duration in patients with chronic hepatitis C virus (HCV) infection. This is usually performed using highly sensitive HCV-RNA assays. However, HCV-RNA assays are time-consuming, expensive and require highly trained personnel. Quantitative determination of HCV core-antigen (HCVAg) levels may be used to supplement treatment monitoring. ObjectivesThe clinical utility of the ARCHITECT HCV Ag assay (Abbott Diagnostics) for response-guided therapy was investigated. Study designWe analyzed serum from 160 patients with HCV genotype 1 infection who had been treated with peg-interferon alfa-2b/ribavirin. HCVAg levels were determined at baseline, weeks 1, 2, 4 and 12. HCVAg levels were compared to those obtained with HCV-RNA assays: VERSANT HCV Quantitative 3.0 (bDNA) and Qualitative (TMA, both Siemens Healthcare) assay and the Abbott RealTime HCV assay (ART; Abbott Diagnostics). ResultsBaseline HCVAg levels correlated well with HCV-RNA as assessed by bDNA (r=0.91; p<0.0001) and ART (r=0.92; p<0.0001), respectively. Patients with undetectable HCVAg levels at week 1 had a 90.9% probability (positive predictive value) to achieve a rapid virologic response (HCV-RNA undetectable at week 4) based on TMA and 86.4% based on ART, respectively. Patients with less than 1log10 reduction in HCVAg between baseline and week 12 had a 90% probability (negative predictive value) to achieve a nonresponse (<2log10 decline in HCV-RNA between baseline and week 12) based on bDNA and 100% based on ART, respectively. ConclusionsDetermination of HCVAg may be useful for antiviral response-monitoring in patients with HCV genotype 1 infection.

Sylatron: A Pegylated Interferon for Use in Melanoma

To review the currently available literature on peginterferon alfa-2b (pegIFN [Sylatron]), including its role in therapy and toxicity for adjuvant treatment of locally advanced melanoma. A literature search was performed of PubMed and the American Society of Clinical Oncology abstracts from 1976 to February 2012, using the primary search terms peginterferon alfa-2b, interferon, Sylatron, and melanoma. All available English-language articles and trials that described the pharmacology, pharmacokinetics, pharmacodynamics, clinical activity, or safety profile of pegIFN were reviewed. PegIFN was approved in March 2011 for the adjuvant treatment of node-positive melanoma. Interferon (IFN) is commonly used in patients with melanoma who remain at high risk for relapse following surgery; however, the optimal scheduling and dose are not agreed upon. Pegylation of IFN involves conjugation with polyethylene glycol. Following subcutaneous injection of pegIFN, the rate of absorption, renal and cellular clearance, and immunogenicity are reduced. As a result of the extended serum half-life, once-weekly administration is feasible, compared with the daily and/or thrice weekly dosing of IFN. When compared with observation alone in patients with resected stage III melanoma, pegIFN demonstrated a significant increase in relapse-free survival, with a marginal impact on overall survival. The most common adverse events were as expected with IFN and included fatigue, increased liver enzymes, pyrexia, headache, anorexia, myalgia, nausea, chills, depression, and injection site reactions. A large Phase 3 study is underway to further assess outcome and toxicity differences between pegIFN weekly and low-dose IFN thrice weekly. PegIFN is a modified version of the previously approved interferon indicated for the adjuvant treatment of melanoma. Although the safety profile remains similar between the pegylated and non-pegylated forms, once-weekly administration is feasible secondary to an extended serum half-life and may have improved convenience for the patient.