2024
Serologic extracellular matrix remodeling markers are related to fibrosis stage and prognosis in a phase 2b trial of simtuzumab in patients with primary sclerosing cholangitis
Thorburn D, Leeming D, Barchuk W, Wang Y, Lu X, Malkov V, Ito K, Bowlus C, Levy C, Goodman Z, Karsdal M, Muir A, Xu J. Serologic extracellular matrix remodeling markers are related to fibrosis stage and prognosis in a phase 2b trial of simtuzumab in patients with primary sclerosing cholangitis. Hepatology Communications 2024, 8: e0467. PMID: 38967589, PMCID: PMC11227354, DOI: 10.1097/hc9.0000000000000467.Peer-Reviewed Original ResearchConceptsPrimary sclerosing cholangitisELF scoreAdvanced fibrosisFibrosis stageFibrosis progressionClinical eventsSclerosing cholangitisExtracellular matrix remodeling markersRemodeling markersPredictors of disease severityPhase 2b trialBaseline to weekPRO-C3Progression to cirrhosisWilcoxon rank sum testMarker of collagen formationType III procollagenModerate diagnostic abilityDiagnosing fibrosis stagesRank sum testSerum markersNoninvasive predictorPrognostic markerModerate prognosisMedian changeProtocol for the development of a core outcome set for clinical trials in primary sclerosing cholangitis
Hussain N, Ma C, Hirschfield G, Walmsley M, Hanford P, Vesterhus M, Kowdley K, Bergquist A, Ponsioen C, Levy C, Assis D, Schramm C, Bowlus C, Trauner M, Aiyegbusi O, Jairath V, Trivedi P. Protocol for the development of a core outcome set for clinical trials in primary sclerosing cholangitis. BMJ Open 2024, 14: e080143. PMID: 38926149, PMCID: PMC11216047, DOI: 10.1136/bmjopen-2023-080143.Peer-Reviewed Original ResearchConceptsPrimary sclerosing cholangitisClinical trialsSclerosing cholangitisCore outcome setImmune-mediated liver diseasesPrimary sclerosing cholangitis treatmentOutcome measuresEvaluate novel therapiesSlow disease progressionPatient-reported outcome measuresMedical therapyNovel therapiesLiver fibrosisDisease progressionHistological assessmentLiver diseaseInternational two-round Delphi surveyImaging-based biomarkersIntervention trialsTherapyConsensus meetingHealthcare payersCholangitisSemistructured qualitative interviewsTwo-round Delphi surveyPatient-focused drug development in primary sclerosing cholangitis: Insights on patient priorities and involvement in clinical trials
Li M, Pai R, Gomel R, Vyas M, Callif S, Hatchett J, Bowlus C, Lai J. Patient-focused drug development in primary sclerosing cholangitis: Insights on patient priorities and involvement in clinical trials. Hepatology Communications 2024, 8: e0433. PMID: 38727680, PMCID: PMC11093571, DOI: 10.1097/hc9.0000000000000433.Peer-Reviewed Original ResearchConceptsPrimary sclerosing cholangitisClinical trialsSclerosing cholangitisDrug trialsTrial participantsMultivariate logistic regressionAssociated with willingnessInflammatory bowel diseaseLong-term riskReferral of patientsDrug developmentTherapy trialsDisease progressionTrial interestBowel diseasePatient-focused drug developmentTreatment trialsPatientsBiopsy requirementsPruritusPatient interestPredictors of patients' willingnessLogistic regressionCholangitisPatients' willingnessA Phase 3 Trial of Seladelpar in Primary Biliary Cholangitis
Hirschfield G, Bowlus C, Mayo M, Kremer A, Vierling J, Kowdley K, Levy C, Villamil A, Ladrón de Guevara Cetina A, Janczewska E, Zigmond E, Jeong S, Yilmaz Y, Kallis Y, Corpechot C, Buggisch P, Invernizzi P, Londoño Hurtado M, Bergheanu S, Yang K, Choi Y, Crittenden D, McWherter C. A Phase 3 Trial of Seladelpar in Primary Biliary Cholangitis. New England Journal Of Medicine 2024, 390: 783-794. PMID: 38381664, DOI: 10.1056/nejmoa2312100.Peer-Reviewed Original ResearchConceptsPrimary biliary cholangitisAlkaline phosphatase levelsPruritus Numerical Rating ScalePercentage of patientsNumerical rating scaleBiliary cholangitisAdverse eventsPhosphatase levelsPlacebo groupUrsodeoxycholic acidPeroxisome proliferator-activated receptor delta agonistBaseline to month 6Severity of adverse eventsAlkaline phosphatase normalizationModerate-to-severe pruritusPlacebo-controlled trialPhase 3 trialUnacceptable side effectsRating ScaleBiochemical responsesBackground therapyDouble-blindDelta agonistsBilirubin levelsMonth 6African American race does not confer an increased risk of clinical events in patients with primary sclerosing cholangitis.
Yazdanfar M, Zepeda J, Dean R, Wu J, Levy C, Goldberg D, Lammert C, Prenner S, Reddy K, Pratt D, Forman L, Assis D, Lytvyak E, Montano-Loza A, Gordon S, Carey E, Ahn J, Schlansky B, Korzenik J, Karagozian R, Hameed B, Chandna S, Yu L, Bowlus C. African American race does not confer an increased risk of clinical events in patients with primary sclerosing cholangitis. Hepatology Communications 2024, 8 PMID: 38285883, PMCID: PMC10830082, DOI: 10.1097/hc9.0000000000000366.Peer-Reviewed Original ResearchConceptsPrimary sclerosing cholangitisTransplant-free survivalInflammatory bowel diseaseHepatic decompensationNon-Hispanic whitesSclerosing cholangitisIncreased risk of clinical eventsNatural history of primary sclerosing cholangitisAssociated with transplant-free survivalHistory of primary sclerosing cholangitisAssociated with hepatic decompensationBowel diseaseProgression to hepatic decompensationRisk of clinical eventsDecompensation-free survivalMayo risk scoreAbnormal liver testsPerformance of prognostic modelsAfrican American raceRates of inflammatory bowel diseaseDeath/liver transplantationAA patientsLiver testsDiagnostic delayAA race
2023
Editorial: The evolving paradigms and treatments for primary biliary cholangitis—Authors' reply
Mayo M, Vierling J, Bowlus C. Editorial: The evolving paradigms and treatments for primary biliary cholangitis—Authors' reply. Alimentary Pharmacology & Therapeutics 2023, 59: 282-282. PMID: 38153281, DOI: 10.1111/apt.17798.Peer-Reviewed Original ResearchEfficacy and Safety of Elafibranor in Primary Biliary Cholangitis
Kowdley K, Bowlus C, Levy C, Akarca U, Alvares-da-Silva M, Andreone P, Arrese M, Corpechot C, Francque S, Heneghan M, Invernizzi P, Jones D, Kruger F, Lawitz E, Mayo M, Shiffman M, Swain M, Valera J, Vargas V, Vierling J, Villamil A, Addy C, Dietrich J, Germain J, Mazain S, Rafailovic D, Taddé B, Miller B, Shu J, Zein C, Schattenberg J. Efficacy and Safety of Elafibranor in Primary Biliary Cholangitis. New England Journal Of Medicine 2023, 390: 795-805. PMID: 37962077, DOI: 10.1056/nejmoa2306185.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAlkaline PhosphataseBilirubinChalconesCholagogues and CholereticsCholestasisDouble-Blind MethodGastrointestinal AgentsHumansLiver Cirrhosis, BiliaryPeroxisome Proliferator-Activated ReceptorsPPAR alphaPPAR deltaPropionatesPruritusTreatment OutcomeUrsodeoxycholic AcidConceptsPrimary biliary cholangitisBiliary cholangitisAlkaline phosphatase levelsPeroxisome proliferator-activated receptorPhosphatase levelsDual peroxisome proliferator-activated receptorLeast-squares mean changeChronic cholestatic liver diseaseItch Numeric Rating ScaleDestruction of interlobular bile ductsModerate-to-severe pruritusPlacebo-controlled trialCholestatic liver diseaseNumerical rating scaleInterlobular bile ductsWorst Itch Numeric Rating ScaleIndicator of cholestasisProliferator-activated receptorsAbdominal painDouble-blindPlacebo groupRelevant biochemical indicatorsAdverse eventsPruritus intensityUrsodeoxycholic acidOpen‐label, clinical trial extension: Two‐year safety and efficacy results of seladelpar in patients with primary biliary cholangitis
Mayo M, Vierling J, Bowlus C, Levy C, Hirschfield G, Neff G, Galambos M, Gordon S, Borg B, Harrison S, Thuluvath P, Goel A, Shiffman M, Swain M, Jones D, Trivedi P, Kremer A, Aspinall R, Sheridan D, Dörffel Y, Yang K, Choi Y, McWherter C. Open‐label, clinical trial extension: Two‐year safety and efficacy results of seladelpar in patients with primary biliary cholangitis. Alimentary Pharmacology & Therapeutics 2023, 59: 186-200. PMID: 37904314, DOI: 10.1111/apt.17755.Peer-Reviewed Original ResearchConceptsPrimary biliary cholangitisBiliary cholangitisLiver injurySerious treatment-related adverse eventsBiochemical markersLong-term extension studyTreatment-related adverse eventsAnti-pruritic effectsClinical trial extensionsSecondary efficacy analysesTwo-Year SafetyUnexpected histological findingsNon-alcoholic steatohepatitisLong-term safetyAdverse eventsElevated bilirubinComposite endpointDose adjustmentEfficacy analysisHistological findingsTrial extensionEfficacy dataEfficacy resultsSelective peroxisomePatients