Prospective study of short-term peginterferon-alpha-2a monotherapy in patients who had a virological response at 2 weeks after initiation of interferon therapy
ABSTRACT Long-term interferon (IFN) therapy is effective in eliminating hepatitis C virus (HCV). However, it carries the risk of adverse effects and reduced quality of life. To assess whether short-term IFN therapy effectively eliminates HCV, we performed a prospective pilot study of pegylated (peg)IFN-alpha-2a therapy for 8 or 24 weeks.
After excluding patients with high titers of genotype-1, 55 HCV patients received pegIFN-alpha-2a. Patients who became negative for HCV-RNA at week 2 were allocated to either an 8-week (n = 19) or 24-week (n = 15) course of IFN. We evaluated the efficacy of and tolerance to IFN therapy.
The sustained virological response rate was excellent in the two groups (8 weeks, 89.5% [17/19]; 24 weeks, 100% [15/15], respectively,). IFN dose reduction was required in one patient of the 8-week group, but in six patients of the 24-week group (P = 0.028). Treatment was completed by all patients of the 8-week group, but discontinued in five patients of the 24-week group (P = 0.011).
The 8-week IFN therapy is more tolerable than the 24-week therapy and had similar outcomes. Excluding the patients with high titers of genotype-1, we recommend switching to an 8-week course of pegIFN-alpha monotherapy once patients show an ultra rapid virological response at week 2 from the start of IFN therapy.
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ABSTRACT: Introduction Condylomata acuminatum is a viral disease characterized by anogenital lesions. Routine therapeutic procedures are tissue destructive. There is evidence to indicate that interferon (IFN) alpha is effective in the treatment of this disease. Patients and methods To evaluate the biological properties, efficacy and tolerability of a new albumin-free recombinant IFN alpha-2b formulation in patients with condylomata acuminatum, 30 patients with a clinical and histopathological diagnosis of this disease were randomly assigned to receive daily intramuscular injections of IFN alpha-2b in three different short therapeutic regimens: 3 × 106 IU for 7 days; 5 × 106 IU for 4 days or 10 × 106 IU for 2 days. All the groups received approximately the same total dose (20 × 106 IU). The primary endpoint consisted of the IFN-induced pharmacodynamic markers β2M and 2’-5’ oligoadenylate synthetase (OAS), which were measured before the first administration and 24 hours after the final dose. Efficacy was evaluated 1 week after each treatment was concluded by comparing the number and diameter (largest and smallest) of the lesions with those of the initial lesions. Additionally, all patients were followed-up for 1 year. Results Serum β2M levels were increased in all patients. A dose-dependent pattern was observed for 2’-5’ OAS, since its induction was significantly higher in patients treated with 10 × 106 IU. The number of lesions was reduced in 12 patients and was increased in only two patients. In more than 60% of the patients, both diameters of the lesions were reduced, but a significant reduction was only observed with the lowest but most often repeated dose. When the groups were analyzed together, these values were also significantly lower at the end of treatment. Overall, 14 patients (46.7%) responded to the treatment. The most common adverse effects were fever, headache, chills and myalgias, none of which were serious. During follow-up, a sustained response was obtained in 62.5% of the responders evaluated with no other clinical interventions. Conclusions This new formulation clearly induces the classical biological markers of IFN in patients with condylomata acuminatum. The results also suggest that a rapid and sustained clinical response can be obtained with a short therapeutic regimen of IFN alpha. Larger, controlled studies should be performed.Piel 07/2009; 24(6):292-299. DOI:10.1016/S0213-9251(09)71644-2
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ABSTRACT: In a country such as Japan with the average age of patients with chronic hepatitis C treated with antivirals sometimes well above 60 years, the standard combination therapy is not well tolerated. In this randomized, prospective, controlled trial, we investigated the efficacy of 24-week peginterferon α monotherapy for easy-to-treat patients. A total of 132 patients chronically infected with hepatitis C virus (HCV) genotype 2 (n = 115) or low viral load HCV genotype 1 (<100 kIU/ml, n = 17) were treated with peginterferon α-2a (180 μg/week). Patients with a rapid virological response (RVR, HCV RNA negative or <500 IU/ml at week 4) were randomized for a total treatment duration of 24 (group A) or 48 (group B) weeks. Patients who did not show RVR (group C) were treated for 48 weeks. Sustained virological response (SVR) was assessed by qualitative reverse-transcription polymerase chain reaction. One hundred eight of 132 (82%) patients with RVR were randomized. SVR rates were 60% (group A), 79% (group B), and 27% (group C), respectively. Similar SVR rates were achieved in patients infected with HCV genotype 2 with low pretreatment viral load (<1000 kIU/ml) in group A (81%) and group B (79%) (P = 0.801), whereas in those with higher viral load (≥1000 kIU/ml), a lower SVR rate was identified in group A (26%) than in group B (67%) (P = 0.041). In conclusion, in patients infected with HCV genotype 2 and pretreatment viral load below 1000 kIU/ml who achieve RVR, 24-week treatment with peginterferon α-2a alone is clinically sufficient. Those who show no RVR or have higher baseline viral load, require alternative therapies.Hepatology International 06/2009; 3(3):468-79. DOI:10.1007/s12072-009-9134-1 · 2.47 Impact Factor
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ABSTRACT: AIM: Elderly and/or cirrhotic patients with hepatitis C virus (HCV) are at high risk of adverse effects during interferon therapy. The aim of the present study was to evaluate the efficacy, safety and predictive factors for sustained virological response (SVR) of low-dose pegylated interferon-α-2a (PEG IFN-α-2a) monotherapy in elderly and/or cirrhotic patients with HCV genotype-2 or genotype-1 low level infection. METHODS: Sixty-four elderly (≥65 years) and/or cirrhotic patients with HCV genotype-2 or genotype-1 low level (<5 logIU/mL) infection underwent low-dose PEG IFN-α-2a (90 μg/week) monotherapy for 24 weeks. Sixty patients were available for efficacy assessment. RESULTS: SVR was achieved in 78.3%. SVR rates according to genotype-1 low, genotype-2 low and genotype-2 high viral load were 90.0%, 87.1% and 57.9%, respectively. The discontinuation rate was 12.5%. PEG IFN-α-2a was interrupted or discontinued in four patients because of severe thrombocytopenia (<25 000/mm(3) ). The baseline platelet counts of all these patients were less than 70 000/mm(3) . On univariate analysis of factors contributing to SVR, significant differences were noted in viral load, platelet count, γ-glutamyltransferase, ferritin, α-fetoprotein level and rapid viral response (RVR). On multivariate analysis, RVR was the only independent factor (P = 0.010, odds ratio = 47.27). The positive and negative SVR-predictive values based on RVR were 95% and 82%, respectively. CONCLUSION: Low-dose PEG IFN-α-2a monotherapy was effective and tolerable in elderly and/or cirrhotic patients with genotype-2 or genotype-1 low HCV level infection. However, a baseline platelet count of more than 70 000/mm(3) is needed for safety. RVR can predict SVR accurately.Hepatology Research 11/2012; 43(7). DOI:10.1111/hepr.12024 · 2.22 Impact Factor