Alimentary Pharmacology & Therapeutics, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 28, 2025
We thank Vuppalanchi R. and Liangpunsakul S. for highlighting our recent article entitled "Clinical Trial to Assess the Safety Tolerability of Anti-IL 23 Monoclonal Antibody Guselkumab in Patients With Alcohol-Associated Liver Disease" (ALD) [1, 2]. This Phase 1 dose-escalation study included patients with ≥ 2 Diagnostic Statistical Manual Mental Disorders, Fifth Edition (DSM-5) criteria alcohol use disorder (AUD) [3], significant hepatic steatosis based on magnetic resonance imaging-proton density fat fraction (MRI-PDFF) 8%, elastography (MRE) < 3.63 kPa. was administered subcutaneously days 29 safe doses up 100 mg, without serious adverse events or changes liver enzymes over time. also observed reductions peripheral cytokines time, including IL-17, IL-23, IL-1β, TNF-α. acknowledge limitations raised this editorial, focus early-stage ALD absence a control group [1]. However, it is important highlight that main objective clinical trial assessment safety profile associated Guselkumab. Consequently, we excluded severe phenotypes avoid exposure those advanced stages ALD, while placebo not due dose-elevation nature its design. agree further studies comparing could provide better insights into efficacy reducing inflammation lowering intake. latter aspect particularly relevant trials involving intake mitigate Hawthorne effect. Of note, explores new standards conducting non-invasive biomarkers identify fibrosis. biopsy has been traditionally considered gold standard assessing fibrosis treatment response [4]. an expensive invasive procedure carries potential risks, interpretation scoring results are subject inter- intra-observer variability [5]. Thus, tests facilitate development trials, increasing number participants costs Moreover, selection AUD self-reported questionnaires current past DSM-5 [2]. approach, together phosphatidylethanol (PEth) testing at enrollment—as performed trial—could individuals [6, 7]. Finally, despite high prevalence overall population significance [8, 9], underrepresented research within disease field [10]. Additionally, there substantial heterogeneity among targeting fibrosis, chronic decompensated disease, alcohol-associated hepatitis. Therefore, promotes novel pharmacological therapies innovative designs. Given these findings, data emerging from promising, IL-23/IL-17 pathway more warranted. Luis Antonio Díaz: conceptualization, investigation, writing – original draft, methodology, validation, visualization, review editing, curation. Rohit Loomba: funding acquisition, project administration, supervision, curation, resources. The authors have nothing report. Loomba serves as consultant Aardvark Therapeutics, Altimmune, Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse bio, Hightide, Inipharma, Intercept, Inventiva, Ionis, Janssen Inc., Madrigal, Metacrine NGM Biopharmaceuticals, Novartis, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89 Terns Pharmaceuticals Viking Therapeutics. In addition, his institutions received grants Boehringer-Ingelheim, Galectin Galmed Hanmi, Janssen, Madrigal Sonic Incytes Pharmaceuticals. He co-founder LipoNexus Inc. linked Diaz et al papers. To view articles, visit https://doi.org/10.1111/apt.70026 https://doi.org/10.1111/apt.70045. Data sharing applicable no were created analyzed study.
Language: Английский