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Peginterferon alfa-2a response

MedGen UID:
776494
Concept ID:
CN184128
Sign or Symptom
Synonym: Pegasys response
Drug:
Peginterferon alfa-2a
MedGen UID:
97775
Concept ID:
C0391001
Pharmacologic Substance
A covalent conjugate of recombinant interferon alfa, subtype 2a, and polyethylene glycol (PEG), used as an antiviral and antineoplastic agent. The biological activity of this agent is derived from its interferon alpha-2a protein moiety. Interferons alfa bind to specific cell-surface receptors, leading to the transcription and translation of genes whose protein products mediate antiviral, antiproliferative, anticancer and immune-modulating effects. The PEG moiety lowers the clearance of interferon alpha-2a, thereby extending the duration of its therapeutic effects, but may also reduce interferon-mediated stimulation of an immune response. (NCI04) [from NCI]
 
Gene (location): IFNL3 (19q13.2)

Definition

PEG-interferon alpha (PEG-IFN 2a and 2b, or PEG-IFN alpha), in combination with ribavirin, is used to treat Hepatitis C Virus (HCV) infection. IFNL3 (also known as IL28B) is a member of the type 3 IFN-alpha family, which are induced by viruses and inhibit HCV replication in vitro. Genetic variants in IFNL3 are associated with increased response (higher sustained virological response rate) to PEG-interferon alpha/ribavirin combination therapy and clearance of HCV. In 2011, the protease inhibitors boceprevir and telaprevir were approved to treat HCV genotype 1 infection in many countries, including the United States and those in the European Union, and are now included in HCV combination therapy. IFNL3 genotype predicts response to this combination therapy and also predicts eligibility for shorter duration of therapy. Guidelines regarding the clinical use of PEG-interferon alpha containing regimens based on IFNL3 genotype have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and are available on the PharmGKB website. [from PharmGKB]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

Huang Y, Li MH, Hou M, Xie Y
Hepatobiliary Pancreat Dis Int 2017 Oct 15;16(5):470-479. doi: 10.1016/S1499-3872(17)60044-4. PMID: 28992878
Chopp S, Vanderwall R, Hult A, Klepser M
Am J Health Syst Pharm 2015 Sep 1;72(17):1445-55. doi: 10.2146/ajhp140290. PMID: 26294237
Rajender Reddy K, Modi MW, Pedder S
Adv Drug Deliv Rev 2002 Jun 17;54(4):571-86. doi: 10.1016/s0169-409x(02)00028-5. PMID: 12052715

Recent clinical studies

Etiology

Asselah T, Chulanov V, Lampertico P, Wedemeyer H, Streinu-Cercel A, Pântea V, Lazar S, Placinta G, Gherlan GS, Bogomolov P, Stepanova T, Morozov V, Syutkin V, Sagalova O, Manuilov D, Mercier RC, Ye L, Da BL, Chee G, Lau AH, Osinusi A, Bourliere M, Ratziu V, Pol S, Hilleret MN, Zoulim F
N Engl J Med 2024 Jul 11;391(2):133-143. Epub 2024 Jun 6 doi: 10.1056/NEJMoa2314134. PMID: 38842520
Liapakis AM, Jacobson I
Liver Int 2012 Feb;32 Suppl 1:17-25. doi: 10.1111/j.1478-3231.2011.02708.x. PMID: 22212567
Sonneveld MJ, Janssen HL
Liver Int 2011 Jan;31 Suppl 1:78-84. doi: 10.1111/j.1478-3231.2010.02384.x. PMID: 21205142
Bacon BR
Am J Manag Care 2004 Mar;10(2 Suppl):S30-40. PMID: 15084065
Baker DE
Rev Gastroenterol Disord 2001;1(2):87-99. PMID: 12120178

Diagnosis

Rodriguez-Torres M, Lawitz E, Yangco B, Jeffers L, Han SH, Thuluvath PJ, Rustgi V, Harrison S, Ghalib R, Vierling JM, Luketic V, Zamor PJ, Ravendhran N, Morgan TR, Pearlman B, O'Brien C, Khallafi H, Pyrsopoulos N, Kong G, McPhee F, Yin PD, Hughes E, Treitel M
Ann Hepatol 2016 Nov-Dec 2016;15(6):834-845. doi: 10.5604/16652681.1222098. PMID: 27740516
Dandri M, Petersen J
Minerva Gastroenterol Dietol 2016 Mar;62(1):88-102. Epub 2015 Oct 8 PMID: 26448309
Liaw YF
Liver Int 2013 Feb;33 Suppl 1:111-5. doi: 10.1111/liv.12057. PMID: 23286854
Hadziyannis SJ
Liver Int 2011 Jan;31 Suppl 1:129-34. doi: 10.1111/j.1478-3231.2010.02406.x. PMID: 21205150
Poynard T, Yuen MF, Ratziu V, Lai CL
Lancet 2003 Dec 20;362(9401):2095-100. doi: 10.1016/s0140-6736(03)15109-4. PMID: 14697814

Therapy

Asselah T, Chulanov V, Lampertico P, Wedemeyer H, Streinu-Cercel A, Pântea V, Lazar S, Placinta G, Gherlan GS, Bogomolov P, Stepanova T, Morozov V, Syutkin V, Sagalova O, Manuilov D, Mercier RC, Ye L, Da BL, Chee G, Lau AH, Osinusi A, Bourliere M, Ratziu V, Pol S, Hilleret MN, Zoulim F
N Engl J Med 2024 Jul 11;391(2):133-143. Epub 2024 Jun 6 doi: 10.1056/NEJMoa2314134. PMID: 38842520
Hauser G, Awad T, Thorlund K, Štimac D, Mabrouk M, Gluud C
Cochrane Database Syst Rev 2014 Feb 28;2014(2):CD005642. doi: 10.1002/14651858.CD005642.pub3. PMID: 24585451Free PMC Article
Liapakis AM, Jacobson I
Liver Int 2012 Feb;32 Suppl 1:17-25. doi: 10.1111/j.1478-3231.2011.02708.x. PMID: 22212567
Zeuzem S, Welsch C, Herrmann E
Semin Liver Dis 2003;23 Suppl 1:23-8. doi: 10.1055/s-2003-41631. PMID: 12934165
Baker DE
Rev Gastroenterol Disord 2001;1(2):87-99. PMID: 12120178

Prognosis

Dandri M, Petersen J
Minerva Gastroenterol Dietol 2016 Mar;62(1):88-102. Epub 2015 Oct 8 PMID: 26448309
Martinot-Peignoux M, Lapalus M, Asselah T, Marcellin P
Liver Int 2014 Feb;34 Suppl 1:97-107. doi: 10.1111/liv.12403. PMID: 24373085
Rockstroh JK
Curr Opin Infect Dis 2006 Feb;19(1):8-13. doi: 10.1097/01.qco.0000200294.22661.e0. PMID: 16374211
Zeuzem S, Welsch C, Herrmann E
Semin Liver Dis 2003;23 Suppl 1:23-8. doi: 10.1055/s-2003-41631. PMID: 12934165
Rajender Reddy K, Modi MW, Pedder S
Adv Drug Deliv Rev 2002 Jun 17;54(4):571-86. doi: 10.1016/s0169-409x(02)00028-5. PMID: 12052715

Clinical prediction guides

Yu J, Xu D
Contrast Media Mol Imaging 2022;2022:7623832. Epub 2022 Sep 28 doi: 10.1155/2022/7623832. PMID: 36247853Free PMC Article
Rodriguez-Torres M, Lawitz E, Yangco B, Jeffers L, Han SH, Thuluvath PJ, Rustgi V, Harrison S, Ghalib R, Vierling JM, Luketic V, Zamor PJ, Ravendhran N, Morgan TR, Pearlman B, O'Brien C, Khallafi H, Pyrsopoulos N, Kong G, McPhee F, Yin PD, Hughes E, Treitel M
Ann Hepatol 2016 Nov-Dec 2016;15(6):834-845. doi: 10.5604/16652681.1222098. PMID: 27740516
Rockstroh JK
Curr Opin Infect Dis 2006 Feb;19(1):8-13. doi: 10.1097/01.qco.0000200294.22661.e0. PMID: 16374211
Reddy KR
Semin Liver Dis 2004;24 Suppl 2:33-8. doi: 10.1055/s-2004-832926. PMID: 15346244
Zeuzem S, Welsch C, Herrmann E
Semin Liver Dis 2003;23 Suppl 1:23-8. doi: 10.1055/s-2003-41631. PMID: 12934165

Recent systematic reviews

Peters van Ton AM, Gevers TJ, Drenth JP
J Viral Hepat 2015 Dec;22(12):965-73. Epub 2015 Mar 11 doi: 10.1111/jvh.12403. PMID: 25760481
Hauser G, Awad T, Thorlund K, Štimac D, Mabrouk M, Gluud C
Cochrane Database Syst Rev 2014 Feb 28;2014(2):CD005642. doi: 10.1002/14651858.CD005642.pub3. PMID: 24585451Free PMC Article
Katz LH, Goldvaser H, Gafter-Gvili A, Tur-Kaspa R
Cochrane Database Syst Rev 2012 Sep 12;2012(9):CD008516. doi: 10.1002/14651858.CD008516.pub2. PMID: 22972122Free PMC Article
Singal AK, Jampana SC, Anand BS
Dig Dis Sci 2011 Aug;56(8):2221-6. Epub 2011 Jun 4 doi: 10.1007/s10620-011-1765-0. PMID: 21643737
Jain MK, Zoellner C
Expert Opin Pharmacother 2010 Mar;11(4):673-83. doi: 10.1517/14656560903580001. PMID: 20163278

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