{"doi":"10.1038/s41392-024-01987-x","title":"Ruxolitinib plus steroids for acute graft versus host disease: a multicenter, randomized, phase 3 trial","abstract":"<jats:title>Abstract</jats:title><jats:p>Newly diagnosed patients with high-risk acute graft-versus-host disease (aGVHD) often experience poor clinical outcomes and low complete remission rates. Ruxolitinib with corticosteroids showed promising efficacy in improving response and failure free survival in our phase I study. This study (ClinicalTrials.gov: NCT04061876) sought to evaluate the safety and effectiveness of combining ruxolitinib (RUX, 5 mg/day) with corticosteroids (1 mg/kg/day methylprednisolone, RUX/steroids combined group) versus using methylprednisolone alone (2 mg/kg/day, steroids-only group). Newly diagnosed patients with intermediate- or high-risk aGVHD were included, with risk levels classified by either the Minnesota aGVHD Risk Score or biomarker assessment. Patients were randomized in a ratio of 1:1 into 2 groups: 99 patients received RUX combined with methylprednisolone, while the other 99 received methylprednisolone alone as the initial treatment. The RUX/steroids group showed a significantly higher overall response rate (ORR) on day 28 (92.9%) compared to the steroids-only group (70.7%, Odds Ratio [OR] = 5.8; 95% Confidence Interval [CI], 2.4–14.0; <jats:italic>P</jats:italic> &lt; 0.001). Similarly, the ORR on day 56 was higher in the RUX/steroids group (85.9% vs. 46.5%; OR = 7.07; 95% CI, 3.36–15.75; <jats:italic>P</jats:italic> &lt; 0.001). Additionally, the 18-month failure-free survival was significantly better in the RUX/steroids group (57.2%) compared to the steroids-only group (33.3%; Hazard Ratio = 0.46; 95% CI, 0.31–0.68; <jats:italic>P</jats:italic> &lt; 0.001). Adverse events (AEs) frequencies were comparable between both groups, with the exception of fewer grade 4 AEs in the RUX/steroids group (26.3% vs. 50.5% <jats:italic>P</jats:italic> = 0.005). To our knowledge, this study is the first prospective, randomized controlled trial to demonstrate that adding ruxolitinib to the standard methylprednisolone regimen provides an effective and safe first-line treatment for newly diagnosed high-risk acute GVHD.</jats:p>","journal":"Signal Transduction and Targeted Therapy","year":2024,"id":651179,"datarank":0.4493598410330987,"base_score":2.995732273553991,"endowment":2.995732273553991,"self_citation_contribution":0.4493598410330987,"citation_network_contribution":0.0,"self_endowment_contribution":0.4493598410330987,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1310445,"name":"Yanli Zhao","orcid":"0000-0002-2948-6951","position":1,"is_corresponding":false},{"id":1252719,"name":"Jingjing Yang","orcid":"0000-0002-7915-7881","position":2,"is_corresponding":false},{"id":51189,"name":"Lei Deng","orcid":null,"position":3,"is_corresponding":false},{"id":1192748,"name":"Nan Wang","orcid":"0000-0002-4290-8987","position":4,"is_corresponding":false},{"id":1386907,"name":"Xiawei Zhang","orcid":"0000-0003-4070-9228","position":5,"is_corresponding":false},{"id":1091243,"name":"Qingyang Liu","orcid":"0000-0003-4062-6764","position":6,"is_corresponding":false},{"id":1445821,"name":"Yan Yang","orcid":"0000-0003-1135-8406","position":7,"is_corresponding":false},{"id":43199,"name":"Zhijie Wei","orcid":null,"position":8,"is_corresponding":false},{"id":1698161,"name":"Fuxu Wang","orcid":null,"position":9,"is_corresponding":false},{"id":1698162,"name":"Yifan Jiao","orcid":null,"position":10,"is_corresponding":false},{"id":108153,"name":"Fei Li","orcid":"0000-0003-0720-3129","position":11,"is_corresponding":false},{"id":1698163,"name":"Songhua Luan","orcid":null,"position":12,"is_corresponding":false},{"id":1698164,"name":"Liangding Hu","orcid":null,"position":13,"is_corresponding":false},{"id":1698165,"name":"Sujun Gao","orcid":null,"position":14,"is_corresponding":false},{"id":1698166,"name":"Chuanfang Liu","orcid":null,"position":15,"is_corresponding":false},{"id":4286,"name":"Xiangjun Liu","orcid":"0000-0002-0119-2134","position":16,"is_corresponding":false},{"id":1124639,"name":"Jinsong Yan","orcid":"0000-0003-4109-2602","position":17,"is_corresponding":false},{"id":1400258,"name":"Xuejun Zhang","orcid":"0000-0001-7689-4686","position":18,"is_corresponding":false},{"id":1406358,"name":"Fang Zhou","orcid":"0000-0001-8401-0457","position":19,"is_corresponding":false},{"id":634356,"name":"Peihua Lu","orcid":"0000-0002-6331-7369","position":20,"is_corresponding":false},{"id":1558914,"name":"Daihong Liu","orcid":"0000-0001-5606-4394","position":21,"is_corresponding":false},{"id":1485634,"name":"Liping Dou","orcid":"0000-0001-7352-9560","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Ruxolitinib plus steroids for acute graft versus host disease: a multicenter, randomized, phase 3 trial","abstract":"<jats:title>Abstract</jats:title><jats:p>Newly diagnosed patients with high-risk acute graft-versus-host disease (aGVHD) often experience poor clinical outcomes and low complete remission rates. Ruxolitinib with corticosteroids showed promising efficacy in improving response and failure free survival in our phase I study. This study (ClinicalTrials.gov: NCT04061876) sought to evaluate the safety and effectiveness of combining ruxolitinib (RUX, 5 mg/day) with corticosteroids (1 mg/kg/day methylprednisolone, RUX/steroids combined group) versus using methylprednisolone alone (2 mg/kg/day, steroids-only group). Newly diagnosed patients with intermediate- or high-risk aGVHD were included, with risk levels classified by either the Minnesota aGVHD Risk Score or biomarker assessment. Patients were randomized in a ratio of 1:1 into 2 groups: 99 patients received RUX combined with methylprednisolone, while the other 99 received methylprednisolone alone as the initial treatment. The RUX/steroids group showed a significantly higher overall response rate (ORR) on day 28 (92.9%) compared to the steroids-only group (70.7%, Odds Ratio [OR] = 5.8; 95% Confidence Interval [CI], 2.4–14.0; <jats:italic>P</jats:italic> &lt; 0.001). Similarly, the ORR on day 56 was higher in the RUX/steroids group (85.9% vs. 46.5%; OR = 7.07; 95% CI, 3.36–15.75; <jats:italic>P</jats:italic> &lt; 0.001). Additionally, the 18-month failure-free survival was significantly better in the RUX/steroids group (57.2%) compared to the steroids-only group (33.3%; Hazard Ratio = 0.46; 95% CI, 0.31–0.68; <jats:italic>P</jats:italic> &lt; 0.001). Adverse events (AEs) frequencies were comparable between both groups, with the exception of fewer grade 4 AEs in the RUX/steroids group (26.3% vs. 50.5% <jats:italic>P</jats:italic> = 0.005). To our knowledge, this study is the first prospective, randomized controlled trial to demonstrate that adding ruxolitinib to the standard methylprednisolone regimen provides an effective and safe first-line treatment for newly diagnosed high-risk acute GVHD.</jats:p>","is_dataset_classified":null,"base_score":2.995732273553991,"endowment":2.995732273553991,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39438467","pmcid":"PMC11496732","openalex_id":"https://openalex.org/W4403625850","authors":[],"funders":[],"total_grants":0,"fwci":5.7602,"citation_percentile":0.96900359,"influential_citations":0,"citation_trend":[{"year":2024,"count":1},{"year":2025,"count":12},{"year":2026,"count":6}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.nature.com/articles/s41392-024-01987-x.pdf","host_type":"journal"},{"url":"https://www.nature.com/articles/s41392-024-01987-x.pdf","host_type":"publisher"},{"url":"https://www.nature.com/articles/s41392-024-01987-x","host_type":"publisher"},{"url":"https://doi.org/10.1038/s41392-024-01987-x","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39438467","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11496732","host_type":"repository"},{"url":"https://doaj.org/article/90a2558a440147a28ae8ba0f14f32491","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11496732/pdf/41392_2024_Article_1987.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC11496732","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11496732?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Hematopoietic Stem Cell Transplantation","Acute Myeloid Leukemia Research","Platelet Disorders and Treatments","Humans","Graft vs Host Disease","Nitriles","Pyrimidines","Pyrazoles","Female","Male","Middle Aged","Adult","Methylprednisolone","Aged","Acute Disease","Steroids","Adolescent"],"mesh_terms":["Acute Disease","Adolescent","Adult","Aged","Female","Graft vs Host Disease","Humans","Male","Methylprednisolone","Middle Aged","Nitriles","Pyrazoles","Pyrimidines","Steroids"],"keywords":["Medicine","Methylprednisolone","Hazard ratio","Internal medicine","Odds ratio","Randomized controlled trial","Ruxolitinib","Gastroenterology","Confidence interval","Adverse effect","Clinical endpoint","Corticosteroid","Bone marrow"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T06:46:55.427589Z","pmid":null,"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":[]}