Safety and Efficacy of Ledipasvir–Sofosbuvir With or Without Ribavirin for Chronic Hepatitis C in Children Ages 6‐11
Currently, there are no interferon‐free treatments available for hepatitis C virus (HCV)–infected patients younger than 12 years. We evaluated the safety and effectiveness of the all‐oral regimen ledipasvir–sofosbuvir ± ribavirin in HCV‐infected children aged 6 to
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| Veröffentlicht in: | Hepatology (Baltimore, Md.) Md.), 2018-12, Vol.68 (6), p.2158-2166 |
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| creator | Murray, Karen F. Balistreri, William F. Bansal, Sanjay Whitworth, Suzanne Evans, Helen M. Gonzalez‐Peralta, Regino P. Wen, Jessica Massetto, Benedetta Kersey, Kathryn Shao, Jiang Garrison, Kimberly L. Parhy, Bandita Brainard, Diana M. Arnon, Ronen Gillis, Lynette A. Jonas, Maureen M. Lin, Chuan‐Hao Narkewicz, Michael R. Schwarz, Kathleen Rosenthal, Philip |
| description | Currently, there are no interferon‐free treatments available for hepatitis C virus (HCV)–infected patients younger than 12 years. We evaluated the safety and effectiveness of the all‐oral regimen ledipasvir–sofosbuvir ± ribavirin in HCV‐infected children aged 6 to |
| doi_str_mv | 10.1002/hep.30123 |
| format | Article |
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We evaluated the safety and effectiveness of the all‐oral regimen ledipasvir–sofosbuvir ± ribavirin in HCV‐infected children aged 6 to <12 years. In an open‐label study, patients aged 6 to <12 years received ledipasvir 45 mg–sofosbuvir 200 mg as two fixed‐dose combination tablets 22.5/100 mg once daily, with or without ribavirin, for 12 or 24 weeks, depending on HCV genotype and cirrhosis status. The primary efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Twelve patients underwent intensive pharmacokinetic sampling to confirm the appropriateness of the ledipasvir and sofosbuvir dosages. Ninety‐two patients were enrolled (88 genotype 1, 2 genotype 3, and 2 genotype 4), with a median age of 9 years (range, 6‐11). Most were perinatally infected (97%) and treatment‐naive (78%). Two were confirmed to have cirrhosis, while the degree of fibrosis was unknown in 55 patients. The overall SVR12 rate was 99% (91/92; 95% confidence interval, 94%‐100%). The single patient not reaching SVR relapsed 4 weeks after completing 12 weeks of treatment. The most common adverse events were headache and pyrexia. One patient had three serious adverse events, which were considered to be not related to study treatment: tooth abscess, abdominal pain, and gastroenteritis. The area under the concentration–time curve and maximum concentration values for sofosbuvir, its primary metabolite GS‐331007, and ledipasvir were within predefined pharmacokinetic equivalence boundaries (50%‐200%) compared to values in adults in phase 2/3 of the ledipasvir and sofosbuvir studies. Conclusion: Ledipasvir–sofosbuvir was well tolerated and highly effective in children 6 to <12 years old with chronic HCV.</description><identifier>ISSN: 0270-9139</identifier><identifier>EISSN: 1527-3350</identifier><identifier>DOI: 10.1002/hep.30123</identifier><identifier>PMID: 30070726</identifier><language>eng</language><publisher>United States: Wolters Kluwer Health, Inc</publisher><subject>Antiviral drugs ; Children ; Cirrhosis ; Fever ; Fibrosis ; Gastroenteritis ; Genotype & phenotype ; Genotypes ; Headache ; Hepatitis ; Hepatitis C ; Hepatology ; Interferon ; Liver cirrhosis ; Pain ; Patients ; Ribavirin ; Tablets ; Teeth</subject><ispartof>Hepatology (Baltimore, Md.), 2018-12, Vol.68 (6), p.2158-2166</ispartof><rights>2018 by the American Association for the Study of Liver Diseases.</rights><rights>Copyright © 2018 by the American Association for the Study of Liver Diseases.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3883-767588805b5a9aee65b1c51b4ead53a410160717dcbd62435a3a54be629707bc3</citedby><cites>FETCH-LOGICAL-c3883-767588805b5a9aee65b1c51b4ead53a410160717dcbd62435a3a54be629707bc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fhep.30123$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fhep.30123$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30070726$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Murray, Karen F.</creatorcontrib><creatorcontrib>Balistreri, William F.</creatorcontrib><creatorcontrib>Bansal, Sanjay</creatorcontrib><creatorcontrib>Whitworth, Suzanne</creatorcontrib><creatorcontrib>Evans, Helen M.</creatorcontrib><creatorcontrib>Gonzalez‐Peralta, Regino P.</creatorcontrib><creatorcontrib>Wen, Jessica</creatorcontrib><creatorcontrib>Massetto, Benedetta</creatorcontrib><creatorcontrib>Kersey, Kathryn</creatorcontrib><creatorcontrib>Shao, Jiang</creatorcontrib><creatorcontrib>Garrison, Kimberly L.</creatorcontrib><creatorcontrib>Parhy, Bandita</creatorcontrib><creatorcontrib>Brainard, Diana M.</creatorcontrib><creatorcontrib>Arnon, Ronen</creatorcontrib><creatorcontrib>Gillis, Lynette A.</creatorcontrib><creatorcontrib>Jonas, Maureen M.</creatorcontrib><creatorcontrib>Lin, Chuan‐Hao</creatorcontrib><creatorcontrib>Narkewicz, Michael R.</creatorcontrib><creatorcontrib>Schwarz, Kathleen</creatorcontrib><creatorcontrib>Rosenthal, Philip</creatorcontrib><title>Safety and Efficacy of Ledipasvir–Sofosbuvir With or Without Ribavirin for Chronic Hepatitis C in Children Ages 6‐11</title><title>Hepatology (Baltimore, Md.)</title><addtitle>Hepatology</addtitle><description>Currently, there are no interferon‐free treatments available for hepatitis C virus (HCV)–infected patients younger than 12 years. We evaluated the safety and effectiveness of the all‐oral regimen ledipasvir–sofosbuvir ± ribavirin in HCV‐infected children aged 6 to <12 years. In an open‐label study, patients aged 6 to <12 years received ledipasvir 45 mg–sofosbuvir 200 mg as two fixed‐dose combination tablets 22.5/100 mg once daily, with or without ribavirin, for 12 or 24 weeks, depending on HCV genotype and cirrhosis status. The primary efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Twelve patients underwent intensive pharmacokinetic sampling to confirm the appropriateness of the ledipasvir and sofosbuvir dosages. Ninety‐two patients were enrolled (88 genotype 1, 2 genotype 3, and 2 genotype 4), with a median age of 9 years (range, 6‐11). Most were perinatally infected (97%) and treatment‐naive (78%). Two were confirmed to have cirrhosis, while the degree of fibrosis was unknown in 55 patients. The overall SVR12 rate was 99% (91/92; 95% confidence interval, 94%‐100%). The single patient not reaching SVR relapsed 4 weeks after completing 12 weeks of treatment. The most common adverse events were headache and pyrexia. One patient had three serious adverse events, which were considered to be not related to study treatment: tooth abscess, abdominal pain, and gastroenteritis. The area under the concentration–time curve and maximum concentration values for sofosbuvir, its primary metabolite GS‐331007, and ledipasvir were within predefined pharmacokinetic equivalence boundaries (50%‐200%) compared to values in adults in phase 2/3 of the ledipasvir and sofosbuvir studies. Conclusion: Ledipasvir–sofosbuvir was well tolerated and highly effective in children 6 to <12 years old with chronic HCV.</description><subject>Antiviral drugs</subject><subject>Children</subject><subject>Cirrhosis</subject><subject>Fever</subject><subject>Fibrosis</subject><subject>Gastroenteritis</subject><subject>Genotype & phenotype</subject><subject>Genotypes</subject><subject>Headache</subject><subject>Hepatitis</subject><subject>Hepatitis C</subject><subject>Hepatology</subject><subject>Interferon</subject><subject>Liver cirrhosis</subject><subject>Pain</subject><subject>Patients</subject><subject>Ribavirin</subject><subject>Tablets</subject><subject>Teeth</subject><issn>0270-9139</issn><issn>1527-3350</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp1kcFq3DAQhkVoSDZpD3mBIuilPTgZSZZsH4PZdAsLCU1Lj0KS5a6C13IlO83e8giBvmGepGqc9FDoaZiZj5-Z_0fohMApAaBnGzucMiCU7aEF4bTIGOPwCi2AFpBVhFWH6CjGGwCocloeoEMGUEBBxQLdXavWjjus-gYv29YZZXbYt3htGzeoeOvC4_2va9_6qKfU4G9u3GA_Vz-N-LPTKs1dj9s0rTfB987glR3U6EYXcY3Tqt64rgm2x-ffbcTi8f6BkNdov1VdtG-e6zH6erH8Uq-y9eXHT_X5OjOsLFlWiIKXZQlcc1UpawXXxHCic6sazlROgAgoSNEY3QiaM66Y4rm2glbpQ23YMXo_6w7B_5hsHOXWRWO7TvXWT1FSKClUpMxFQt_9g974KfTpOkmTibmgkEOiPsyUCT7GYFs5BLdVYScJyD9xyBSHfIojsW-fFSe9tc1f8sX_BJzNwE_X2d3_leRqeTVL_gZEtpPl</recordid><startdate>201812</startdate><enddate>201812</enddate><creator>Murray, Karen F.</creator><creator>Balistreri, William F.</creator><creator>Bansal, Sanjay</creator><creator>Whitworth, Suzanne</creator><creator>Evans, Helen M.</creator><creator>Gonzalez‐Peralta, Regino P.</creator><creator>Wen, Jessica</creator><creator>Massetto, Benedetta</creator><creator>Kersey, Kathryn</creator><creator>Shao, Jiang</creator><creator>Garrison, Kimberly L.</creator><creator>Parhy, Bandita</creator><creator>Brainard, Diana M.</creator><creator>Arnon, Ronen</creator><creator>Gillis, Lynette A.</creator><creator>Jonas, Maureen M.</creator><creator>Lin, Chuan‐Hao</creator><creator>Narkewicz, Michael R.</creator><creator>Schwarz, Kathleen</creator><creator>Rosenthal, Philip</creator><general>Wolters Kluwer Health, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>201812</creationdate><title>Safety and Efficacy of Ledipasvir–Sofosbuvir With or Without Ribavirin for Chronic Hepatitis C in Children Ages 6‐11</title><author>Murray, Karen F. ; 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We evaluated the safety and effectiveness of the all‐oral regimen ledipasvir–sofosbuvir ± ribavirin in HCV‐infected children aged 6 to <12 years. In an open‐label study, patients aged 6 to <12 years received ledipasvir 45 mg–sofosbuvir 200 mg as two fixed‐dose combination tablets 22.5/100 mg once daily, with or without ribavirin, for 12 or 24 weeks, depending on HCV genotype and cirrhosis status. The primary efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Twelve patients underwent intensive pharmacokinetic sampling to confirm the appropriateness of the ledipasvir and sofosbuvir dosages. Ninety‐two patients were enrolled (88 genotype 1, 2 genotype 3, and 2 genotype 4), with a median age of 9 years (range, 6‐11). Most were perinatally infected (97%) and treatment‐naive (78%). Two were confirmed to have cirrhosis, while the degree of fibrosis was unknown in 55 patients. The overall SVR12 rate was 99% (91/92; 95% confidence interval, 94%‐100%). The single patient not reaching SVR relapsed 4 weeks after completing 12 weeks of treatment. The most common adverse events were headache and pyrexia. One patient had three serious adverse events, which were considered to be not related to study treatment: tooth abscess, abdominal pain, and gastroenteritis. The area under the concentration–time curve and maximum concentration values for sofosbuvir, its primary metabolite GS‐331007, and ledipasvir were within predefined pharmacokinetic equivalence boundaries (50%‐200%) compared to values in adults in phase 2/3 of the ledipasvir and sofosbuvir studies. Conclusion: Ledipasvir–sofosbuvir was well tolerated and highly effective in children 6 to <12 years old with chronic HCV.</abstract><cop>United States</cop><pub>Wolters Kluwer Health, Inc</pub><pmid>30070726</pmid><doi>10.1002/hep.30123</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| source | Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Antiviral drugs Children Cirrhosis Fever Fibrosis Gastroenteritis Genotype & phenotype Genotypes Headache Hepatitis Hepatitis C Hepatology Interferon Liver cirrhosis Pain Patients Ribavirin Tablets Teeth |
| title | Safety and Efficacy of Ledipasvir–Sofosbuvir With or Without Ribavirin for Chronic Hepatitis C in Children Ages 6‐11 |
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