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RESEARCH PRODUCT
Real-world experience with obeticholic acid in patients with primary biliary cholangitis
Anna MorgandoMauro ViganòAna LleoMaurizio PompiliElisabetta De GasperiDaphne D’amatoAlessandro MussettoCazzagon NPietro InvernizziFrancesca ColapietroVincenzo RoncaSara LabancaEster VanniM.r. CannavòFrancesco LositoErnesto ClaarG. ScifoGiovanni GalatiUmberto Vespasiani-gentilucciSilvia StoratoAlessio GerussiGrazia Anna NiroAntonio IzziBarbara OmazziAntonio De VincentisValentina FelettiGiuseppe GrassiValeria Pace PalittiClara MancusoVincenza CalvarusoEvelise FrazzettoRoberto BoldizzoniMarco MarzioniFloriano RosinaAndrea PalermoAntonino PicciottoValentina BelliaGaetano BertinoItalian Pbc RegistryGuido PoggiRodolfo SaccoDomenico AlvaroLuigi MuratoriMaria VinciMarie Graciella PigozziRaffaele CozzolongoNatalia TerreniAnnarosa FloreaniMaurizio RusselloMarco DistefanoRinaldo PellicanoMaria D'antòMarco CarboneRosanna VenereR. FontanaAntonio PicardiSilvia CasellaS. E. O'donnellFederica MalinvernoStefano FagiuoliLaura CristoferiLuchino ChessaGiacomo MulinacciPietro PozzoniAntonino CastellanetaGiulia MarconiAdriano M. PellicelliFrancesca Romana PonzianiLeonardo Baiocchisubject
upper limit of normalCirrhosisALTAMAAutoimmunityantinuclear antibodiesULNPBCGastroenterologyUDCASettore MED/12ULN upper limit of normalobeticholic acidaRR adjusted risk ratio.CRFs case record formAST aspartate transferaseClinical endpointGGT gamma-glutamyl transferaseQCprimary biliary cholangitisGastroenterologyUrsodeoxycholic acidANATCCCirrhosisCholestasiTIPSTreatment Completer CohortANA antinuclear antibodiemedicine.medical_specialtyRRUDCA ursodeoxycholic acidTIPS transjugular intrahepatic portosystemic shuntOCACirrhosiALP alkaline phosphataseautoimmune hepatitismedicine.diseasedigestive system diseasesDiscontinuationKeywords: AIH autoimmune hepatitiQC quality controlchemistrygamma-glutamyl transferaserandomised controlled trialelectronic data captureantimitochondrial antibodiesaspartate transferaseAutoimmune hepatitischemistry.chemical_compoundAIHCRFsImmunology and Allergyadjusted risk ratioANA antinuclear antibodiesRR risk ratioOverall cohortALT alanine transferaseAMA antimitochondrial antibodieCholestasisCRFs case record formsObeticholic acidOverlap PBC-AIHursodeoxycholic acidOCA obeticholic acidTolerabilityalkaline phosphataseRCTResearch Articlemedicine.drugcase record formsContext (language use)AMA antimitochondrial antibodiesInternal medicineEDC electronic data capturetransjugular intrahepatic portosystemic shuntInternal MedicinemedicineRCT randomised controlled trialaRR adjusted risk ratioOClcsh:RC799-869quality controlalanine transferaseASTaRRHepatologybusiness.industryAutoimmunity; Cholestasis; Cirrhosis; Overlap PBC-AIHAIH autoimmune hepatitisTCC Treatment Completer CohortPBC primary biliary cholangitiGGTrisk ratioOC Overall cohortALPlcsh:Diseases of the digestive system. GastroenterologyPBC primary biliary cholangitisbusinessEDCdescription
Background & aims Obeticholic acid (OCA) is the second-line treatment approved for patients with primary biliary cholangitis (PBC) and an inadequate response or intolerance to ursodeoxycholic acid. We aimed to evaluate the effectiveness and safety of OCA under real-world conditions. Methods Patients were recruited into the Italian PBC Registry, a multicentre, observational cohort study that monitors patients with PBC at national level. The primary endpoint was the biochemical response according to Poise criteria; the secondary endpoint was the biochemical response according to normal range criteria, defined as normal levels of bilirubin, alkaline phosphatase (ALP), and alanine aminotransferase (ALT) at 12 months. Safety and tolerability were also assessed. Results We analysed 191 patients until at least 12 months of follow-up. Median age was 57 years, 94% female, 61 (32%) had cirrhosis, 28 (15%) had histologically proven overlap with autoimmune hepatitis (PBC-AIH). At 12 months, significant median reductions of ALP (-32.3%), ALT (-31.4%), and bilirubin (-11.2%) were observed. Response rates were 42.9% according to Poise criteria, and 11% by normal range criteria. Patients with cirrhosis had lower response than patients without cirrhosis (29.5% vs. 49.2%, p = 0.01), owing to a higher rate of OCA discontinuation (30% vs. 12%, p = 0.004), although with similar ALP reduction (29.4% vs. 34%, p = 0.53). Overlap PBC-AIH had a similar response to pure PBC (46.4% vs. 42.3%, p = 0.68), with higher ALT reduction at 6 months (-38% vs. -29%, p = 0.04). Thirty-three patients (17%) prematurely discontinued OCA because of adverse events, of whom 11 experienced serious adverse events. Treatment-induced pruritus was the leading cause of OCA discontinuation (67%). Conclusions Effectiveness and safety of OCA under real-world conditions mirror those in the Poise trial. Patients with cirrhosis had lower tolerability. Overlap PBC-AIH showed higher ALT reduction at 6 months compared with patients with pure PBC. Lay summary Obeticholic acid (OCA) was shown to be effective in more than one-third of patients not responding to ursodeoxycholic acid in a real-world context in Italy. Patients with cirrhosis had more side effects with OCA, and this led to suspension of the drug in one-third of patients. OCA was also effective in patients who had overlap between autoimmune hepatitis and primary biliary cholangitis.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2021-04-01 |