Recombinant alfa-interferon plus ribavirin therapy in children and adolescents with chronic hepatitis C

Wirth, Stéfan; Lang, Thomas; Gehring, Stephan; Gerner, Patrick

doi:10.1053/jhep.2002.36495

Cited by 107 publications

(88 citation statements)

References 27 publications

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“…Our studies demonstrate that interferon alfa-2b in combination with oral ribavirin is effective and reasonably safe for the treatment of childhood chronic hepatitis C. Infection with HCV genotypes 2 or 3, and lower level of serum HCV RNA at baseline in HCV genotype 1, are associated with higher virological response rates. These results are consistent with those reported in small pediatric pilot [18][19][20][21] and large adult studies. 7,8 SVR rates in children with chronic HCV given interferon alfa-2b with ribavirin in these studies are higher than in those using interferon alone (46% vs. 36%, respectively).…”

Section: Discussionsupporting

confidence: 93%

“…Most events, such as insomnia, irritability, and somnolence, were mild to moderate in severity. In addition, depression, a side effect not previously reported in children with chronic HCV infection given interferon alone 23 or with ribavirin, [18][19][20][21] occurred in 13% of subjects. This may reflect the fact that the protocols were designed to identify and monitor depressive symptoms.…”

Section: Discussionmentioning

confidence: 88%

“…The overall pattern of adverse events, hematological changes, and discontinuations from treatment is consistent with that seen in pediatric subjects treated with interferon alone or in combination with ribavirin. [18][19][20][21] The adverse event profile in children is also similar to that seen in adults treated with comparable regimens. 7,8 The most common adverse events consisted of influenza-like symptoms and gastrointestinal complaints, including fever, headache, anorexia, vomiting, abdominal pain, myalgia, and nausea.…”

Section: Discussionmentioning

confidence: 99%

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Interferon Alfa-2b in Combination With Ribavirin for the Treatment of Chronic Hepatitis C in Children: Efficacy, Safety, and Pharmacokinetics *

et al. 2005

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Chronic hepatitis C virus (HCV) infection is usually asymptomatic in children, but significant liver disease may occur. We evaluated the efficacy, safety, and pharmacokinetics of interferon alfa-2b and ribavirin in children with chronic HCV. We determined the optimal ribavirin dose in an initial cohort of a phase 1 study and then subsequently used it, in combination with interferon alfa-2b, in a second cohort of this study and a phase 3 trial. The primary efficacy endpoint in all studies was sustained virological response, defined by undetectable serum HCV RNA 24 weeks after completion of therapy. All efficacy and safety analyses were performed on the intent-to-treat population. Children receiving interferon alfa-2b plus ribavirin 15 mg/kg/d in the phase 1 study had the maximum reduction in serum HCV RNA at treatment weeks 4 and 12 with an acceptable safety profile. This ribavirin dose was selected as optimal and used in all subsequent studies. In all, 46% (54/118) of optimally treated children achieved sustained virological response. Sustained virological response was significantly higher in children with HCV genotype 2/3 (84%) than in those with HCV genotype 1 (36%). Adverse events led to dose modification in 37 (31%) and discontinuation in 8 (7%). Multiple-dose interferon alfa-2b and ribavirin peak and trough concentrations and area-under-the-curve were similar between children and adults. In conclusion, interferon alfa-2b in combination with ribavirin is effective and safe in children with chronic hepatitis C virus. (HEPATOLOGY 2005;42:1010-1018.) H epatitis C virus (HCV) infection is a global health problem affecting an estimated 170 million individuals worldwide. Although our understanding about the natural history and pathobiology of HCV infection in children is incomplete, it has been associated with significant liver disease, including chronic hepatitis, cirrhosis, and hepatocellular carcinoma in this population. 1-4 Approximately 10% to 20% of adults 5 and 36% of children 6 treated with interferon alone achieve long-term virological remission. The addition of ribavirin to interferon-based regimens markedly improves virological responses in adults. 7,8 Limited data are available regarding the use of interferon alfa with ribavirin in children. Therefore, the aim of our studies was to evaluate the efficacy, safety, and pharmacokinetics of interferon alfa-2b in combination with ribavirin for the treatment of chronic HCV infection in children. Patients and Methods Study DesignA clinical program consisting of two studies was initiated to evaluate the efficacy, safety, and pharmacokinetics of interferon alfa-2b (Intron A, Schering-Plough, KenAbbreviations: HCV, hepatitis C virus; MIU, million international units; PCR, polymerase chain reaction; TSH, thyroid-stimulating hormone; ALT, alanine aminotransferase; SVR, sustained virological response. From the

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Interferon Alfa-2b in Combination With Ribavirin for the Treatment of Chronic Hepatitis C in Children: Efficacy, Safety, and Pharmacokinetics *

et al. 2005

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“…14 Thyroid abnormalities following interferon therapy have also been described in children receiving interferon for hepatitis C infection. 15 Some of these complications of IFN␣ therapy, especially thyrotoxicosis, can be severe and may interfere with adequate interferon therapy in patients with hepatitis C. 13,[16][17][18] Moreover, because the symptoms of hypothyroidismsuch as fatigue, hair loss, myalgia, and weight gain-may be attributable to hepatitis C or IFN␣ therapy, 8 the diagnosis of hypothyroidism in these patients may be delayed. This delay may lead to development of further complications.…”

mentioning

confidence: 99%

The clinical and physiological spectrum of interferon‐alpha induced thyroiditis

et al. 2006

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Interferon-alpha (IFN␣) is a major treatment modality for several malignant and nonmalignant diseases, especially hepatitis C. Prospective studies have shown that up to 15% of patients with hepatitis C receiving IFN␣ develop clinical thyroid disease, and up to 40% were reported to develop thyroid antibodies. Some of these complications may result in discontinuation of interferon therapy. Thus, interferon induced thyroiditis (IIT) is a major clinical problem for patients receiving interferon therapy. IIT can be classified as autoimmune type and non-autoimmune type. I nterferons were discovered in the 1950Јs and were immediately recognized for their ability to render cells resistant to virus infection. 1 Interferons have been classified into two major groups, type I interferons and type II interferons, based on their capacity to bind to common receptor types. Type I interferons bind to a type I interferon receptor and include interferon-␣, interferon-␤, interferon-, and interferon-. 2 Type II interferons bind to a distinct type II receptor and include interferon-␥. 2 In addition to their antiviral properties, interferons have immunomodulatory, antiangiogenic, antiproliferative and antitumor activity, and act as important regulators of growth and differentiation. 3 Interferons work by directly binding to either type I or type II receptors. The cytoplasmic domains of the transmembrane glycoproteins are associated with members of the JAK family of kinases. They activate various signaling pathways, including the JAK-STAT pathway, the Crk-pathway, the IRS signaling pathway, and the MAP kinase pathway, which leads to signal transduction and subsequent activation or repression of specific genes. 3,4 More than twenty interferon-induced proteins have been identified. 5 Interferon-alpha (IFN␣) was the first cytokine to be reproduced by recombinant DNA technology and has emerged as a major therapeutic modality for several malignant and nonmalignant diseases. Among the diseases treated by IFN␣ are melanoma, renal cell carcinoma, hairy cell leukemia, Kaposi's sarcoma, and hepatitis B and C. 5 However, the most common prescription for IFN␣

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“…Currently, the only Food and Drug Administration‐approved options for children with chronic HCV infection are ribavirin (RBV) and pegylated‐interferon (PEG‐IFN). While sustained viral responses (SVRs) have improved over the last several decades from ∼16% with IFN monotherapy to >50% with the combination of RBV and PEG‐IFN, multiple studies have shown that SVR rates remain frustratingly low compared to adults with access to DAA regimens 6, 13, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116. Consequently, in the absence of approved DAA therapies in the United States, the chance of attaining SVR in HCV‐infected children and adolescents is little more than 50% (Table 4).…”

Section: Managementmentioning

confidence: 99%