Clinical Trial to Assess the Safety and Tolerability of Anti-IL 23 Monoclonal Antibody Guselkumab in Patients With Alcohol-Associated Liver Disease

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dc.catalogadorjlo
dc.contributor.authorDíaz Piga, Luis Antonio
dc.contributor.authorMorris, Sheldon
dc.contributor.authorDave, Shravan
dc.contributor.authorKim, Susy M.
dc.contributor.authorSarik, Wathnita
dc.contributor.authorRichards, Lisa
dc.contributor.authorMadamba, Egbert
dc.contributor.authorBettencourt, Ricki
dc.contributor.authorFulinara, Christian
dc.contributor.authorPham, Thuy
dc.contributor.authorMiller, Grant
dc.contributor.authorCarvalho-Gontijo Weber, Raquel
dc.contributor.authorMomper, Jeremiah D.
dc.contributor.authorHe, Feng
dc.contributor.authorJain, Sonia
dc.contributor.authorJamieson, Catriona
dc.contributor.authorKisseleva, Tatiana
dc.contributor.authorBrenner, David
dc.contributor.authorLoomba, Rohit
dc.date.accessioned2025-03-11T15:38:29Z
dc.date.available2025-03-11T15:38:29Z
dc.date.issued2025
dc.description.abstractBackgroundThere are no FDA-approved therapies for alcohol-associated liver disease (ALD). Preclinical studies indicate that blocking IL-23/IL-17 signalling may reverse liver injury. Guselkumab, an IL-23-specific antibody approved for psoriasis, may be beneficial for ALD. AimsWe aimed to assess the safety and tolerability of guselkumab in patients with ALD. MethodsThis phase-1 dose-escalation study included patients with >= 2 DSM-5 criteria for alcohol use disorder, significant steatosis (MRI-PDFF >= 8%) and MRE < 3.63 kPa (to exclude advanced disease). Guselkumab was given subcutaneously on Days 1 and 29 in 30, 70 or 100 mg dose cohorts. Primary endpoints were adverse events (AEs) and dose-limiting toxicity. ResultsWe enrolled 13 patients (three 30 mg, three 70 mg, and seven 100 mg). Eleven completed the study and two early discontinued in the 100 mg group. Of them, 77% were men, and the median age was 53 [IQR 49-61] years. The median MRI-PDFF and MRE were 18.4% [IQR 8.4%-34.0%] and 2.5 [2.2-2.6] kPa, respectively. The most frequent AEs were hyperuricemia (13%, mild only) and elevated lipase (11%, mild and moderate). There were no serious adverse events or significant variations in liver enzymes. There was a suppression of peripheral interleukin (IL)-17, IL-23, IL-1b and TNF-alpha in the 70 and 100 mg groups, and a significant decrease in alcohol consumption over time (AUDIT-C: 6 [3-7] vs. 5 [1-6], p = 0.023). Conclusions Guselkumab is safe in doses up to 100 mg and may reduce inflammation markers in ALD. These findings support further phase 2 studies to evaluate the efficacy of guselkumab in ALD, particularly in patients with severe phenotypes.
dc.fechaingreso.objetodigitalNo aplica
dc.fuente.origenWOS
dc.identifier.doi10.1111/apt.70026
dc.identifier.eissn1365-2036
dc.identifier.issn0269-2813
dc.identifier.urihttps://doi.org/10.1111/apt.70026
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/102490
dc.identifier.wosidWOS:001421560400001
dc.information.autorucEscuela de Medicina; Díaz Piga, Luis Antonio; 0000-0002-8540-4930; 179253
dc.language.isoen
dc.nota.accesosin adjunto
dc.revistaAlimentary Pharmacology & Therapeutics
dc.rightsregistro bibliográfico
dc.subjectAlcoholic cirrhosis
dc.subjectAlcohol-related liver disease
dc.subjectALD
dc.subjectCirrhosis
dc.subjectLiver disease
dc.subjectSteatotic liver disease
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.titleClinical Trial to Assess the Safety and Tolerability of Anti-IL 23 Monoclonal Antibody Guselkumab in Patients With Alcohol-Associated Liver Disease
dc.typepreprint
sipa.codpersvinculados179253
sipa.trazabilidadWOS;2025-03-01
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