{"doi":"10.1093/immadv/ltab022","title":"A phase 1b open-label dose-finding study of ustekinumab in young adults with type 1 diabetes","abstract":"OBJECTIVES: We assessed the safety of ustekinumab (a monoclonal antibody used in psoriasis to target the IL-12 and IL-23 pathways) in a small cohort of recent-onset (<100 days of diagnosis) adults with type 1 diabetes (T1D) by conducting a pilot open-label dose-finding and mechanistic study (NCT02117765) at the University of British Columbia. METHODS: We sequentially enrolled 20 participants into four subcutaneous dosing cohorts: (i) 45 mg loading weeks 0/4/16, (ii) 45 mg maintenance weeks 0/4/16/28/40, (iii) 90 mg loading weeks 0/4/16, and (iv) 90 mg maintenance weeks 0/4/16/28/40. The primary endpoint was safety as assessed by an independent data and safety monitoring board (DSMB) but we also measured mixed meal tolerance test C-peptide, insulin use/kg, and HbA1c. Immunophenotyping was performed to assess immune cell subsets and islet antigen-specific T cell responses. RESULTS: Although several adverse events were reported, only two (bacterial vaginosis and hallucinations) were thought to be possibly related to drug administration by the study investigators. At 1 year, the 90 mg maintenance dosing cohort had the smallest mean decline in C-peptide area under the curve (AUC) (0.1 pmol/ml). Immunophenotyping showed that ustekinumab reduced the percentage of circulating Th17, Th1, and Th17.1 cells and proinsulin-specific T cells that secreted IFN-γ and IL-17A. CONCLUSION: Ustekinumab was deemed safe to progress to efficacy studies by the DSMB at doses used to treat psoriasis in adults with T1D. A 90 mg maintenance dosing schedule reduced proinsulin-specific IFN-γ and IL-17A-producing T cells. Further studies are warranted to determine if ustekinumab can prevent C-peptide AUC decline and induce a clinical response.","journal":"Immunotherapy Advances","year":2021,"id":175895,"datarank":0.7775429916362888,"base_score":3.1354942159291497,"endowment":3.1354942159291497,"self_citation_contribution":0.47032413238937254,"citation_network_contribution":0.30721885924691633,"self_endowment_contribution":0.47032413238937254,"citer_contribution":0.30721885924691633,"corpus_percentile":null,"corpus_rank":null,"citation_count":22,"citer_count":17,"citers_with_citation_signal":16,"citers_with_endowment":16,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.833,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02117765"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":718457,"name":"Samuel Chow","orcid":null,"position":1,"is_corresponding":false},{"id":717727,"name":"Anne M. Pesenacker","orcid":"0000-0002-7968-0277","position":2,"is_corresponding":false},{"id":717728,"name":"Laura Cook","orcid":"0000-0003-3153-2045","position":3,"is_corresponding":false},{"id":718458,"name":"Annika C. Sun","orcid":null,"position":4,"is_corresponding":false},{"id":308289,"name":"S. Alice Long","orcid":"0000-0002-0281-1240","position":5,"is_corresponding":false},{"id":717729,"name":"Jennie H. M. Yang","orcid":"0000-0001-6171-833X","position":6,"is_corresponding":false},{"id":717730,"name":"Kirsten A. Ward‐Hartstonge","orcid":"0000-0003-1225-0843","position":7,"is_corresponding":false},{"id":717731,"name":"Evangelia Williams","orcid":"0000-0002-5348-7313","position":8,"is_corresponding":false},{"id":717732,"name":"Clara Domingo‐Vila","orcid":"0000-0002-1086-4684","position":9,"is_corresponding":false},{"id":718459,"name":"Khalif Halani","orcid":null,"position":10,"is_corresponding":false},{"id":256536,"name":"Kristina M. Harris","orcid":"0000-0002-6957-514X","position":11,"is_corresponding":false},{"id":393223,"name":"Timothy Tree","orcid":"0000-0002-6973-5377","position":12,"is_corresponding":false},{"id":685436,"name":"Megan K. Levings","orcid":"0000-0002-0305-5790","position":13,"is_corresponding":false},{"id":231202,"name":"Thomas G. Elliott","orcid":"0000-0002-4626-6440","position":14,"is_corresponding":false},{"id":266199,"name":"Rusung Tan","orcid":"0000-0002-2204-2004","position":15,"is_corresponding":false},{"id":696573,"name":"Jan Dutz","orcid":"0000-0003-3035-0522","position":16,"is_corresponding":false},{"id":717726,"name":"Ashish Marwaha","orcid":"0000-0003-1234-0224","position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":null,"created_at":"2026-07-18T23:47:19.591542Z","pmid":"35072168","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":[]}