6533b7d1fe1ef96bd125c1b7

RESEARCH PRODUCT

Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohort.

Study Group Guard CT HassaneinG BakalosS AhlersMl ShiffmanL TallaricoKr ReddyA OrlandiniP FerenciM DerbalaC CoppolaGr FosterJ BashoG ShabanajA HarxhiN DebziN AfredjN GuessabN MahindadH MahiouM AissaouiJ Al QameeshZ Al GhandoorC AsseneB BastensC BrixkoM CoolC De GalocsyJ DelwaideC GeorgeP LaukensV LefebvreJp MulkayF NevensB ServaisH Van VlierbergheY HorsmansJ HenrionD SprengersP MichielsenS BourgeoisL LasserP LangletG RobaeysJp MartinetP WarzeeP HosteH ReynaertI JuriensJ DecaesteckerF Van Der MeerschF JanssensS AhmetagicA VerhazM BevandaL CalkicN IbrahimpasicR MesihovicCe MelloFj RuizE Martins JuniorMl FerrazG SilvaC MendesA LyraMh SilvaG GomideJc FernandesP PereiraMc CorreaR TeixeiraA YousryA HannoM GabrA OmarG EsmatS KaratapanisV NikolopoulouG GiannoulisS ManolakopoulosI ElefsiniotisC DrakoulisD DimitroulopoulosS KanatakisI KetikoglouK MimidisN EvgenidisE AkriviadesI Vafiadi ZoubouliE TsianosM MelaE OrfanouG MousoulisI KaragiannisE ManesisM VargaE NemesánszkyK FriedJ SchullerF SzalayG LengyelI TornaiT BanyaiM LeschI NagyJ GervainA TusnadiF SchneiderL SzentgyörgyiB HunyadyA VinczeG TolvajI VarkonyiE MakkaiJ EnyediI RaczP HausingerZ VácziÁ PataiZ OzsvárL LaknerP RibiczeyA BhallaS SomaniR LuaiaP RaoM PhilipP LawateA NagralA SoodS ParikhS MeratM Nassiri ToosiSm AlavianMr ZaliNe DaryaniD DrenaggiAf AttiliF BandieraP BassiG BellatiS BellantaniMaurizia Rossana BrunettoS BrunoF CastelliR CastellacciAm CattelanM ColomboC CoppolaA CraxiS D'angeloS ColomboL DemeliaG Di PerriA Di GiacomoC FerrariD FrancisciK CasinelliR GangaC CostaA MangiaFp RussoF MatarazzoG MazzellaM MazzeoM MemoliM MontalbanoG MontaltoA PieriN PassarielloA PicciottoA PietrangeloM PirisiT QuirinoG RaimondoGl RapacciniG RizzardiniM RizzettoM RusselloG SabuscoT SantantonioG SoardoL TallaricoA AmedeaG VerucchiF VinelliAl ZignegoM ZuinA AscioneM VinciMg PigozziP TundoGm SaraccoP AmorosoM AndreoniC CollettaE ErneAs MegnaA BiglinoP ChiriacoG FotiG SpinziE D'amicoSw PaikSh AhnYn LeeY KimJ YangSy HanR VargheseA Al GharaballyH AskarA ShararaC YaghiAa RachedZ HoumaniF ZaarourA DohaibiL IvanovskiN JoksimovicZ AbbasS MemonA MohsinS MasoodZ HashmiW HalotaZ DeronW MazurR FlisiakA LipczynskiJ MusialikA PiekarskaK AugustyniakB Baka CwierzK SimonA GietkaH BerakJ SiekluckiD RadowskaB SzlauerT PiekosI OlszokM JablkowskiG OrszulakI WarakomskaMj AleixoC ValenteG MacedoR Sarmento CastroF RoxoT FariaK MansinhoJ VelezJp RamosH GuerreiroS AlbertoC MonteverdeF SerejoP PeixeJ MalhadoM DerbalaM CurescuA Streinu CercelF CaruntuH LiviaL PreotescuV AramaI AncutaL GheorgheC StanciuA TrifanM AcalovschiV AndreicaO PascuM LencuI SporeaD OlteanuF Ionita RaduC Fierbinteanu BraticeviciA MotocR SilaghiM MusatF ComanM StanC CijevschiE MiftodeD DelicR JesicD NozicP SvorcanM FabriL KonstantinovicM PelemisG JankovicZ TodorovicA NagorniV KupcovaL SkladanyM SzantovaD KrkoskaP JarcuskaI SchreterM OltmanJ BocakovaI BunganicJ HolomanA GiguereA. M. Abdou

subject

Genetics and Molecular Biology (all)MaleChronic HepatitisHepacivirusRibavirin/adverse effectsAsthenia/chemically inducedHepacivirusPolyethylene GlycolBiochemistryPolyethylene GlycolsBody Mass IndexChronic Liver Disease0302 clinical medicineNeutropenia/chemically inducedInterferon-alpha/adverse effectsMedicineChroniclcsh:ScienceLiver Diseasesvirus diseasesAntiviral Agents/adverse effectsCohortScience & Technology - Other Topics030211 gastroenterology & hepatologyDrug Therapy CombinationCohort studyHumanmedicine.medical_specialtyAlpha interferonGastroenterology and HepatologyAntiviral AgentsMicrobiologyDose-Response Relationship03 medical and health sciencesPharmacotherapyHepatitis C Chronic/drug therapyDose Prediction MethodsDrug TherapyAnemia/chemically inducedHumansHemoglobinAgedMedicine and health sciencesBiochemistry Genetics and Molecular Biology (all)HepaciviruScience & TechnologyDose-Response Relationship DrugFlaviviruseslcsh:ROrganismsBiology and Life SciencesProteinsmedicine.diseasedigestive system diseaseschemistryAgricultural and Biological Sciences (all)Withholding TreatmentAstheniaImmunologyProportional Hazards Modellcsh:QHuman medicineRNA virusesPhysiologylcsh:MedicinePeginterferon-alfaPolyethylene Glycols/adverse effectsAdult; Aged; Anemia; Antiviral Agents; Asthenia; Cohort Studies; Dose-Response Relationship Drug; Drug Therapy Combination; Female; Hepacivirus; Hepatitis C Chronic; Host-Pathogen Interactions; Humans; Interferon-alpha; Male; Middle Aged; Neutropenia; Outcome Assessment (Health Care); Polyethylene Glycols; Proportional Hazards Models; RNA Viral; Recombinant Proteins; Ribavirin; Withholding Treatment; Agricultural and Biological Sciences (all); Biochemistry Genetics and Molecular Biology (all); Medicine (all)Cohort Studieschemistry.chemical_compoundOutcome Assessment Health CareMedicine and Health Sciences030212 general & internal medicineViralPathology and laboratory medicineMultidisciplinarybiologyHepatitis C virusPharmaceuticsMedicine (all)AnemiaHepatitis CHematologyRecombinant ProteinOutcome Assessment (Health Care)/methodsMiddle AgedMedical microbiologyHepatitis CRecombinant ProteinsHost-Pathogen InteractionMultidisciplinary SciencesPhysiological ParametersResearch DesignCombinationHost-Pathogen InteractionsVirusesRNA ViralFemaleDrugPathogensHost-Pathogen Interactions/drug effectsResearch ArticleAdultNeutropeniaClinical Research DesignResearch and Analysis MethodsOutcome Assessment (Health Care)Internal medicineRibavirinRecombinant Proteins/adverse effectsRNA Viral/bloodAdult; Aged; Anemia; Antiviral Agents; Asthenia; Cohort Studies; Dose-Response Relationship Drug; Drug Therapy Combination; Female; Hepacivirus; Hepatitis C Chronic; Host-Pathogen Interactions; Humans; Interferon-alpha; Male; Middle Aged; Neutropenia; Outcome Assessment (Health Care); Polyethylene Glycols; Proportional Hazards Models; RNA Viral; Recombinant Proteins; Ribavirin; Withholding TreatmentAdult; Aged; Anemia; Antiviral Agents; Asthenia; Cohort Studies; Dose-Response Relationship Drug; Drug Therapy Combination; Female; Hepacivirus; Hepatitis C Chronic; Host-Pathogen Interactions; Humans; Interferon-alpha; Male; Middle Aged; Neutropenia; Outcome Assessment (Health Care); Polyethylene Glycols; Proportional Hazards Models; RNA Viral; Recombinant Proteins; Ribavirin; Withholding Treatment; Medicine (all); Biochemistry Genetics and Molecular Biology (all); Agricultural and Biological Sciences (all)Proportional Hazards ModelsAntiviral Agentbusiness.industryRibavirinBody WeightHepacivirus/drug effectsViral pathogensInterferon-alphaHepatitis C Chronicbiology.organism_classificationHepatitis virusesMicrobial pathogensRNAAdverse EventsCohort Studiebusiness

description

Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. Results: SVR24 rates were 46.1 % (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1,2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. Conclusions: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginter-feron alfa-2a/ribavirin. © 2016 Foster et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

yearjournalcountryeditionlanguage
2015-09-03PloS one
10.1371/journal.pone.0151703https://pubmed.ncbi.nlm.nih.gov/27018988