A Review of Standard and Newer Treatment Strategies in Hepatitis C | Page 2

A head-to-head study of the peginterferon products was conducted to determine the therapy of choice for HCV.10 In the study, patients with HCV genotype 1 who were previously untreated were randomized to undergo 48 weeks of peginterferon alfa-2b 1.5 mcg/kg per week plus ribavirin 800 to 1400 mg per day, or a low dose of 1 mcg/kg per week plus ribavirin 800 to 1400 mg per day, or peginterferon alfa-2a 180 mcg per week plus ribavirin 1000 to 1200 mg per day. SVR was achieved in 39.8% of the standard-dose peginterferon alfa-2b group, 38% of the low-dose peginterferon alfa-2b group, and 40.9% of the peginterferon alfa-2a group (P = NS for all comparisons). Relapse occurred in 23.5%, 20%, and 31.5% of patients, respectively (P value not assessed). However, when HCV RNA was undetectable at week 4, 86.2% achieved an SVR, and when the virus was undetected at week 12, SVR was achieved in 78.7% of patients. The adverse effect profile was similar among all 3 regimens, with more serious adverse events occurring among patients in the peginterferon alfa-2a group (11.7%) than among patients in the standard dose peginterferon alfa-2b group (8.6%, P = .02). Common adverse effects included discontinuation for any reason (low-dose peginterferon alfa-2b, 51.5%; standard-dose peginterferon alfa- 2b, 47%; peginterferon alfa-2a, 40%), discontinuation for virological non-response (low-dose peginterferon alfa-2b, 35.1%; standard-dose peginterferon alfa-2b, 25.7%; peginterferon alfa-2a, 20.4%), neutrophil count less than 750 per mm3 (14.6%-27%), hemoglobin less than 10 g/dL (25.3%- 30.7%), use of an erythrocyte-stimulating agent (14.2%- 16.6%), fatigue (64.4%-66.5%), headache (42.3%-49.9%), nausea (36.4%-42.5%), insomnia (38.3%-41.4%), pyrexia (22.9%-34.9%), anemia (28.8%-33.9%), myalgia (22.5%- 26.9%), neutropenia (18.5%-31.5%), depression (19.4%- 25.5%), irritability (25.1%-25.8%), and rash (21.9%-28%). Dose modification was necessary in 33.3% of patients in the low-dose peginterferon alfa-2b group, 43.3% of patients in the standard-dose peginterferon alfa-2b group, and 42.9% of patients in the peginterferon alfa-2a group; the majority of these involved modification of the ribavirin component of the regimen.10

Peginterferon and ribavirin regimens have also been utilized for other clinical scenarios, including patients with hepatitis C and cirrhosis, patients experiencing treatment failure, and patients co-infected with HIV.11-16 Studies have demonstrated that higher-risk patients had lower SVR rates, ranging from 18% to 35%, and that high-dose ribavirin increased efficacy, but also increased adverse effects, such as anemia. The studies also demonstrated that non-Hispanic white patients had a higher rate of SVR with peginterferon alfa plus ribavirin (52%) than black patients (19%, P <.001), primarily in patients with genotype 1 (98%).16 The results highlight the differential response to treatment based on patient demographic characteristics, and suggest that in most situations, an SVR rate of less than 50% may be expected with standard doses of peginterferon with ribavirin.

Evidence-Based Treatment Guidelines and Limitations of Current Treatment Options

Treatment guidelines focused on standard therapies suggest that treatment decisions should be based on the severity of liver disease, potential for serious adverse effects, likelihood of treatment response, presence of comorbid conditions, and patient acceptance of treatment.3 Although treatment with peginterferon with ribavirin is no longer the standard of care for genotype 1 HCV, it is the foundational regimen for current triple drug regimens, so clinicians should understand the standard approach to treatment.

For patients with genotype 1 and 4, historical guidelines suggested that peginterferon plus ribavirin should be planned for 48 weeks, using peginterferon alfa-2a 180 mcg subcutaneously per week with oral ribavirin 1000 mg for patients weighing 75 kg or less, and ribavirin 1200 mg for patients over 75 kg, or peginterferon alfa-2b 1.5 mcg/kg subcutaneously per week with ribavirin 800 mg for patients up to 65 kg, 1000 mg for patients 65 kg to 85 kg, 1200 mg for patients 85 kg to 105 kg, and 1400 mg for patients over 105 kg. Follow-up HCV RNA testing should occur at week 12 for assessment of EVR, and treatment should be discontinued in patients who do not achieve an EVR. If a complete EVR is obtained, treatment may continue for a total of 48 weeks. For patients with a partial EVR, a 24-week HCV RNA assessment should be conducted, and if negative, treatment should be continued to 48 weeks, and if positive, therapy should be discontinued. In patients with genotype 1 who have delayed virus clearance, therapy may be extended to 72 weeks. Patients who achieve negative HCV RNA should be assessed 24 weeks after treatment for SVR. In patients with genotype 2 or 3, treatment with standard dose peginterferon and ribavirin 800 mg for 24 weeks is recommended. Genotype 2 or 3 patients who achieve negative HCV RNA at 24 weeks should be assessed 24 weeks after treatment for SVR.

Patients with cirrhosis who achieve SVR should be monitored at 6-month intervals for HCC regardless of genotype. Retreatment of patients who fail to achieve SVR after a full course of peginterferon and ribavirin is not recommended. Retreatment (with triple therapy, which is discussed later) may be considered for non-responders, partial responders, and relapsers who have been previously treated with nonpegylated interferon–based therapy or with peginterferon monotherapy. Careful assessment is needed and retreatment risks and benefits must be discussed with patients who were cirrhotic null responders to previous therapy, as these patients appear to have low response rates and high resistance rates to triple therapy. Maintenance with pegylated interferon alone is not recommended for bridging fibrosis or cirrhosis in patients who experienced treatment failure with peginterferon and ribavirin.³