6533b872fe1ef96bd12d4269
RESEARCH PRODUCT
Ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin for patients with hepatitis C virus genotype 1 or 4 infection with cirrhosis (ABACUS): a prospective observational study
Salvatore PettaMarco MarzioniPierluigi RussoAlessio AghemoAlfredo AlbertiAntonio AscioneAndrea AntinoriRaffaele BrunoSavino BrunoAntonio ChirianniGiovanni Battista GaetaEdoardo GianniniManuela MerliVincenzo MessinaSimona MontillaCarlo Federico PernoMassimo PuotiGiovanni RaimondoMaria RendinaFrancesca Ceccherini SilbersteinErica VillaAnna Linda ZignegoLuca PaniAntonio CraxìMarco TaboneMassimo AndreoniElisabetta TetiMario AngelicoMarcello PersicoMario MasaroneAledssandro ChioderaAttilio SolinasMarco Delle MonacheRoberto CecereAnna Maria SchimizziSara PiovesanDavide CampagnoloMaria Chiara PirasTeresa ZolfinoFrancesca Paolo RussoOlivia MorelliVincenzo SangiovanniMirella OnofrioValentina IodiceAntonio IzziMassimo PirisiElena DanieliMaria VinciGiuliano RizzardiniStefano FagiuoliLuisa PasuloAntonella D'arminio MonforteMassimo ZuinAlessia GiorginiFilomena SimeoneGuido PialiCarmela Lo GuercioAlessandro FedericoGiuseppina BrancaccioAldo MarroneGiuseppe AbbatiChiara BoariniVanni BorghiVeronica BernabucciGiampaolo CortiMonica MontiMario RizzettoSilvia MartiniPietro AndreoneAlice GianstefaniMarco LenziGabriella VerucchiPierluigi ToniuttoGuglielmo BorgiaNicola CaporasoFilomena MoriscoGaetano NardoneDebora AngrisaniAndrea GiacomettiAntonio BenedettiGiuseppe TarantinoFabio MarsettiMarcello TavioSergio NovaraTeresa Antonia SantantonioGaetano ServiddioMaurizia BrunettoBarbara CocoGioacchino AngaranoMichele MilellaMichele BaroneAlfredo Di LeoDomenico Ettore SansonnoIrene CacciolaNicola BoffaGiorgio SaraccoAntonio Di BiagioAntonino PicciottoAndrea De LucaVincenza CalvarusoSilvia CorradoriCarlo FerrariAlessandra OrlandiniIvana MaidaCarlo TortiLuchino ChessaMartina FelderUmberto Vespasiani GentilucciPaolo AngeliAntonietta RomanoGian Ludovico RapacciniLuca MieleSerena CimaMaria Luisa RussoRaffaele CozzolongoGiovanna OnnelliGiampiero D'offiziRaffaella LionettiMarzia MontalbanoMichele GuerraGiovanni Di PerriLucio BoglioneFranco CapraGiada CaroloDonatella IeluzziCinzia AntoniniAntonio TermiteSalvatore MadoniaPierluigi TarquiniGiustino ParrutiGiacomo VecchietKatia FalascaBarbara MenzaghiTiziana QuirinoChiara DentoneAnna Maria PiscagliaCristina RossiMaria GiordaniLuca FontanellaGiovanni CassolaMaurizio RusselloAntonio CristaudoVania GiacometMassimo ColomboFrancesca DonatoEmanuele DuranteLucio CoscoMassimo MarignaniMariano QuartiniMassimo MemoliRoberto GangaLaura PontiAlessandro SoriaMaria Grazia RumiRoberto GulminettiRenato MaseratiMario U. MondelliAdriano LazzarinMaria Rita ParisiBenedetta CanovariIvo AvanciniCecilia PravadelliPier BlancCaterina PasquazziClaudio Maria MastroianniMyriam LichtnerMarco DistefanoSilvia MagnaniSimona PaganinElke ErnePietro GattiPaolo TundiPaolo CalabreseAntonio GasbarriniAntonio GriecoNicola CoppolaPaolo Del PoggioMassimo LevreroGloria TallianiVincenzo VulloRoberto CaudaSilvia La MonicaDomenico PotenzaSalvatore RizzoFrancesco CastelliGrazielle Marie PigozziAlessia CiancioDante RomagnoliFederica BarchettiJelena IvanovicOlimpia LongoSandra PetragliaMaria Paola TrottaGerardo Antonio Pio Nardonesubject
CyclopropanesCompassionate Use TrialsLiver CirrhosisMalechemistry.chemical_compound0302 clinical medicine2-NaphthylamineHCV direct-acting antiviral mixed cryoglobulinemia RBVAnilides030212 general & internal medicineLongitudinal StudiesProspective StudiesChronicAdult; Aged; Anilides; Antiviral Agents; Carbamates; Compassionate Use Trials; Drug Therapy Combination; Female; Genotype; Hepatitis C Chronic; Humans; Liver Cirrhosis; Longitudinal Studies; Macrocyclic Compounds; Male; Middle Aged; Prospective Studies; Ribavirin; Ritonavir; Sulfonamides; Treatment Outcome; UracilSettore MED/12 - GastroenterologiaSulfonamidesDasabuvirHCV DAAGastroenterologyvirus diseasesValineMiddle AgedSettore MED/07 - Microbiologia e Microbiologia ClinicaHepatitis CTreatment OutcomeGastroenterology; HepatologyCombinationDrug Therapy Combination030211 gastroenterology & hepatologyFemalemedicine.drugAdultmedicine.medical_specialtyMacrocyclic CompoundsProlineGenotypeLactams MacrocyclicAdult; Aged; Anilides; Antiviral Agents; Carbamates; Compassionate Use Trials; Drug Therapy Combination; Female; Genotype; Hepatitis C Chronic; Humans; Liver Cirrhosis; Longitudinal Studies; Macrocyclic Compounds; Male; Middle Aged; Prospective Studies; Ribavirin; Ritonavir; Sulfonamides; Treatment Outcome; Uracil; Hepatology; GastroenterologyHepatitis C virus genotype 1 Hepatitis C virus genotype 4 decompensated liver cirrhosis antiviral therapy dasabuvir ombitasvir paritaprevirHepatology; GastroenterologyAntiviral Agents03 medical and health sciencesDrug TherapyInternal medicineRibavirinmedicineHumansDecompensationAdverse effectUracilAgedRitonavirHepatologybusiness.industryRibavirinHepatitis C ChronicVirologyOmbitasvirClinical trialchemistryParitaprevirRitonavirCarbamatesbusinessdescription
Summary Background We ran a compassionate use nationwide programme (ABACUS) to provide access to ombitasvir, paritaprevir, and ritonavir, with dasabuvir, plus ribavirin for hepatitis C virus (HCV) genotype 1 infection and ombitasvir, paritaprevir, and ritonavir, plus ribavirin for HCV genotype 4 infection in patients with cirrhosis at high risk of decompensation while approval of these regimens was pending in Italy. Methods In this prospective observational study, we collected data from a compassionate use nationwide programme from March 17, 2014, to May 28, 2015. Patients with HCV genotype 1 infection and cirrhosis at high risk of decompensation were given coformulated ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) once daily and dasabuvir (250 mg) twice daily for 12 weeks (patients with HCV genotype 1b infection) or 24 weeks (patients with HCV genotype 1a infection). Patients with HCV genotype 4 infection were given coformulated ombitasvir (25 mg), paritaprevir (150 mg), and ritonavir (100 mg) once per day for 24 weeks. All patients were given weight-based ribavirin. The primary efficacy endpoint was sustained virological response at week 12 after the end of treatment (SVR12), analysed by intention-to-treat. Univariate and multivariate logistic regression analyses were used to identify baseline characteristics associated with SVR12. Adverse events were recorded throughout the study. Findings 728 (96%) of 762 patients with cirrhosis who were given ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin therapy for 12 or 24 weeks achieved SVR12. Logistic regression analyses identified that bilirubin concentrations of less than 2 mg/dL were associated with SVR12 (odds ratio [OR] 4·76 [95% CI 1·83–12·3]; p=0·001). 166 (23%) of 734 patients included in safety analyses had an adverse event. 25 (3%) patients discontinued treatment because of adverse events. Asthenia was the most commonly reported adverse event, occurring in 36 (5%) patients. Interpretation Our findings suggest that the safety and effectiveness of ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir, plus ribavirin in patients with HCV genotype 1 or 4 infection and cirrhosis at high risk of decompensation in a real-life setting are similar to those reported in clinical trials. The concordance with clinical trials provides reassurance that the reported efficacy of this treatment in clinical trials will translate to its use in routine clinical practice. Funding Dipartimento Biomedico di Medicina Interna e Specialistica dell'Universita di Palermo.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2017-06-01 |