Retreatment of Hepatitis C with Consensus Interferon and Ribavirin After Nonresponse or Relapse to Pegylated Interferon and Ribavirin: A National VA Clinical Practice Study

Dig Dis Sci. 2011 Jun 2. [Epub ahead of print]

 

Yee HS, Currie SL, Tortorice K, Cozen M, Shen H, Chapman S, Cunningham F, Monto A.

 

Gastroenterology Section, Department of Veterans Affairs Medical Center (VAMC), 4150 Clement Street (111B), San Francisco, CA, 94121, USA.

Abstract

BACKGROUND:

Studies of the retreatment with consensus interferon (CIFN) and ribavirin (RBV) of hepatitis C virus (HCV)-infected patients who failed prior pegylated interferon alfa/ribavirin (PEG-IFN/RBV) have found quite variable efficacy and tolerability of this therapy. As such, CIFN/RBV use and efficacy in clinical practice were evaluated within the Department of Veterans Affairs (VA), the largest national, integrated system for HCV care.

AIMS:
The purpose of this study was to determine rates of sustained virologic response (SVR) and patterns of CIFN/RBV use in the VA. Methods included retrospective review of national VA data in HCV-infected patients who had previously failed ≥12 weeks of PEG-IFN/RBV and were prescribed CIFN/RBV between October 1, 2003 and September 30, 2006.

RESULTS:
A total of 597 patients met the study criteria. CIFN was primarily dosed as 15 mcg subcutaneously daily combined with standard doses of RBV. Mean treatment duration was 21 weeks; CIFN was discontinued within 4 weeks in 24%. Hematological growth factors were used in 49%. Post-treatment viral loads were available in 385 patients. SVR to CIFN/RBV was achieved in 11%, and was significantly higher in prior PEG-IFN/RBV relapsers compared with nonresponders (31% vs. 6%, respectively; P < 0.0001). A 2-log(10) or greater drop in HCV RNA after 24 weeks of PEG-IFN/RBV was a predictor of subsequent SVR to CIFN/RBV.

CONCLUSIONS:
CIFN/RBV was used frequently in clinical practice for retreatment of PEG-IFN/RBV. In this setting, early treatment discontinuation was common. Overall SVR was low, although response was significantly better in prior PEG-IFN/RBV relapsers and those who had a 2-log(10) or greater decline than in nonresponders.

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U.S. Multicenter Pilot Study of Daily Consensus Interferon (CIFN) Plus Ribavirin for "Difficult-to-Treat" HCV Genotype 1 Patients

Dig Dis Sci. 2011 Jan 11. [Epub ahead of print]

Ho SB, Aqel B, Dieperink E, Liu S, Tetrick L, Falck-Ytter Y, Decomarmond C, Smith CI, McKee DP, Boyd W, Kulig CC, Bini EJ, Pedrosa MC.

VA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA, 92161, USA, samuel.ho2@va.gov.

Abstract

BACKGROUND: Patients with chronic hepatitis C genotype 1 (HCV-1) and difficult-to-treat characteristics respond poorly to pegylated interferon alfa and ribavirin (RBV), and could benefit from an interferon with increased activity (consensus interferon or CIFN), favorable viral kinetics from daily dosing, and a longer duration of therapy. The purpose of this pilot study was to determine the efficacy and safety of daily CIFN + RBV for initial treatment of patients with HCV-1 infection.

METHODS: Patients with difficult-to-treat characteristics (92% male, 33% African American, 78% Veterans Affairs [VA]; 67% high viral load, 59% stage 3-4 fibrosis, and mean weight of 204 lbs) were enrolled at seven VA and two community medical centers. They were randomized to daily CIFN (15 mcg/day SQ) and RBV (1-1.2 g/d PO) given for either 52 weeks (group A, n = 33) or 52-72 weeks (from time of viral response +48 weeks) (group B, n = 31).

RESULTS: Intention to treat analysis for treatment groups A and B demonstrated 33% (11/33) and 32% (10/31) sustained virologic response (SVR), respectively. Only 2/31 patients in group B received more than 52 weeks of treatment. The overall group demonstrated a 31% (20/64) rapid virologic response rate (RVR), 54% (34/64) end of treatment virologic response and a 33% (21/64) SVR. Patients with RVR at 4 weeks, early virologic response from 8-12 weeks, and late virologic response from 16-24 weeks demonstrated SVR of 75% (15/20), 31% (4/13), and 22% (2/9), respectively. Overall early non-protocol discontinuation occurred in 26/64 (40%) patients.

CONCLUSION: Daily CIFN and ribavirin for initial treatment of HCV-1 patients has potential for achieving a relatively high RVR rate, but discontinuations are frequent and successful use of this regimen is highly dependent on adequate patient support to maintain adherence.

PMID: 21221804 [PubMed - as supplied by publisher]

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Comparative efficacy and overall safety of different doses of consensus interferon for treatment of chronic HCV infection: a systematic review and meta-analysis

European Journal of Clinical Pharmacology
DOI: 10.1007/s00228-010-0881-7

Seyed-Moayed Alavian, Bita Behnava and Seyed Vahid Tabatabaei

Abstract

Background

About one-half of patients with hepatitis C genotype 1 and one-third with genotype 2/3 have treatment failure with peginterferon alpha and ribavirin. Consensus interferon (CIFN) is an option for retreatment of these patients.

Objective

To summarize comparative safety and efficacy of different regimens of CIFN for the treatment of patients with chronic hepatitis C infection.

Data source

Medline, Scopus, ISI, and Cochran Central Register of Clinical Trials were used.

Study eligibility criteria

Randomized clinical trials (RCTs) were eligible for inclusion in the study.

Participants

HIV and HBV seronegative patients with positive HCV-RNA during the 6 months before the start of the study were eligible for inclusion.

Interventions

Different regimens of CIFN were studied.

Study appraisal and synthesis methods

Studies were appraised based on methods of random sequence generation, allocation concealment, and blinding. The random effects model of DerSimonian and Laird was employed to run the meta-analysis. The end-point was sustained virological response (SVR).

Results

Data of 10 RCTs including 1,600 subjects were extracted. High daily induction dose regimen of CIFN did not yield a higher rate of SVR than low daily induction dose treatment regimen, RR = 0.83 (95% CI 0.58–1.17). A dose of 9 μg thrice weekly (tiw) was associated with a significantly higher rate of SVR compared with 3 μg [RR = 3.14 (95% CI 1.68–5.58)]‹. Withdrawal rate was similar [RR = 1.28 (95% CI 0.65–2.50)] but dose modification was higher in 9 μg [RR = 3.22 (95% CI 1.08–9.60)]. A dose of 18/15 μg tiw was not more effective than 9 μg over a similar treatment duration [RR = 1.02 (95% CI 0. 87–1.19)].

Limitations

Limitations include inadequate reporting of methodological information and side effects, lack of publication bias assessment due to the small number of studies in each analysis.

Conclusions

High dose daily induction therapy with CIFN is not superior to low dose therapy in terms of SVR. It seems that 9 μg tiw is the optimal treatment dose of CIFN for treatment of HCV infection. Optimal duration and safety profile of CIFN therapy have yet been elucidated.

Keywords Consensus interferon - Induction therapy - High dose - Low dose - Meta-analysis - Systematic review

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