{"doi":"10.1111/apt.70026","title":"Clinical Trial to Assess the Safety and Tolerability of Anti‐<scp>IL</scp> 23 Monoclonal Antibody Guselkumab in Patients With Alcohol‐Associated Liver Disease","abstract":"BACKGROUND: There 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. AIMS: We aimed to assess the safety and tolerability of guselkumab in patients with ALD. METHODS: This 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. RESULTS: We 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-α 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.","journal":"Alimentary Pharmacology & Therapeutics","year":2025,"id":537989,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9581,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":327416,"name":"Sheldon Morris","orcid":null,"position":1,"is_corresponding":false},{"id":1424182,"name":"Shravan Dave","orcid":"0000-0002-2875-4926","position":2,"is_corresponding":false},{"id":234435,"name":"Susy M. 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Momper","orcid":"0000-0002-3154-6685","position":12,"is_corresponding":false},{"id":233617,"name":"Feng He","orcid":"0000-0003-0276-3303","position":13,"is_corresponding":false},{"id":264448,"name":"Sonia Jain","orcid":"0000-0001-8408-1247","position":14,"is_corresponding":false},{"id":477605,"name":"Catriona Jamieson","orcid":"0000-0001-8057-6613","position":15,"is_corresponding":false},{"id":226038,"name":"Tatiana Kisseleva","orcid":"0000-0001-9107-2306","position":16,"is_corresponding":false},{"id":812865,"name":"David Brenner","orcid":null,"position":17,"is_corresponding":false},{"id":235444,"name":"Rohit Loomba","orcid":"0000-0002-4845-9991","position":18,"is_corresponding":false},{"id":480718,"name":"Luis Antonio Díaz","orcid":"0000-0002-8540-4930","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T02:52:16.891390Z","pmid":"39949265","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}