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dc.contributor.authorMayo, MJ
dc.contributor.authorVierling, JM
dc.contributor.authorBowlus, CL
dc.contributor.authorLevy, C
dc.contributor.authorHirschfield, GM
dc.contributor.authorNeff, GW
dc.contributor.authorGalambos, MR
dc.contributor.authorGordon, SC
dc.contributor.authorBorg, BB
dc.contributor.authorHarrison, SA
dc.contributor.authorThuluvath, PJ
dc.contributor.authorGoel, A
dc.contributor.authorShiffman, ML
dc.contributor.authorSwain, MG
dc.contributor.authorJones, DEJ
dc.contributor.authorTrivedi, P
dc.contributor.authorKremer, AE
dc.contributor.authorAspinall, RJ
dc.contributor.authorSheridan, DA
dc.contributor.authorDörffel, Y
dc.contributor.authorYang, K
dc.contributor.authorChoi, Y
dc.contributor.authorMcWherter, CA
dc.date.accessioned2023-11-28T13:48:25Z
dc.date.available2023-11-28T13:48:25Z
dc.date.issued2023-10-30
dc.identifier.issn0269-2813
dc.identifier.issn1365-2036
dc.identifier.urihttps://pearl.plymouth.ac.uk/handle/10026.1/21755
dc.description.abstract

Background Seladelpar is a potent and selective peroxisome proliferator-activated receptor-δ agonist that targets multiple cell types involved in primary biliary cholangitis (PBC), leading to anti-cholestatic, anti-inflammatory and anti-pruritic effects. Aims To evaluate the long-term safety and efficacy of seladelpar in patients with PBC. Methods In an open-label, international, long-term extension study, patients with PBC completing seladelpar lead-in studies continued treatment. Seladelpar was taken orally once daily at doses of 5 or 10 mg with dose adjustment permitted for safety or tolerability. The primary analysis was for safety and the secondary efficacy analysis examined biochemical markers of cholestasis and liver injury. The study was terminated early due to the unexpected histological findings in a concurrent study for non-alcoholic steatohepatitis, which were subsequently found to predate treatment. Safety and efficacy data were analysed through 2 years. Results There were no serious treatment-related adverse events observed among 106 patients treated with seladelpar for up to 2 years. There were four discontinuations for safety, one possibly related to seladelpar. Among 53 patients who completed 2 years of seladelpar, response rates increased from years 1 to 2 for the composite endpoint (alkaline phosphatase [ALP] <1.67 × ULN, ≥15% decrease in ALP, and total bilirubin ≤ULN) and ALP normalisation from 66% to 79% and from 26% to 42%, respectively. In those with elevated bilirubin at baseline, 43% achieved normalisation at year 2. Conclusions Seladelpar was safe, and markedly improved biochemical markers of cholestasis and liver injury in patients with PBC. These effects were maintained or improved throughout the second year.

dc.format.extent186-200
dc.format.mediumPrint-Electronic
dc.languageen
dc.publisherWiley
dc.subjectHumans
dc.subjectUrsodeoxycholic Acid
dc.subjectLiver Cirrhosis, Biliary
dc.subjectCholestasis
dc.subjectBiomarkers
dc.subjectAlkaline Phosphatase
dc.subjectBilirubin
dc.titleOpen‐label, clinical trial extension: Two‐year safety and efficacy results of seladelpar in patients with primary biliary cholangitis
dc.typejournal-article
dc.typeArticle
plymouth.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/37904314
plymouth.issue2
plymouth.volume59
plymouth.publisher-urlhttp://dx.doi.org/10.1111/apt.17755
plymouth.publication-statusPublished
plymouth.journalAlimentary Pharmacology &amp; Therapeutics
dc.identifier.doi10.1111/apt.17755
plymouth.organisational-group|Plymouth
plymouth.organisational-group|Plymouth|Faculty of Health
plymouth.organisational-group|Plymouth|REF 2021 Researchers by UoA
plymouth.organisational-group|Plymouth|Users by role
plymouth.organisational-group|Plymouth|Users by role|Academics
plymouth.organisational-group|Plymouth|REF 2021 Researchers by UoA|UoA01 Clinical Medicine
plymouth.organisational-group|Plymouth|Faculty of Health|Peninsula Medical School
plymouth.organisational-group|Plymouth|REF 2028 Researchers by UoA
plymouth.organisational-group|Plymouth|REF 2028 Researchers by UoA|UoA01 Clinical Medicine
dc.publisher.placeEngland
dcterms.dateAccepted2023-09-26
dc.date.updated2023-11-28T13:48:25Z
dc.rights.embargodate2023-12-6
dc.identifier.eissn1365-2036
rioxxterms.versionofrecord10.1111/apt.17755


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