{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T18:42:40Z","timestamp":1788979360681,"version":"build-2803163510"},"reference-count":41,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hematology Reports"],"abstract":"<jats:p>Background\/Objectives: VEXAS (Vacuoles, E1-Enzyme, X-linked, Autoinflammatory, and Somatic) syndrome is a recently described adult-onset autoinflammatory disorder. It is characterized by somatic mutations in the UBA1 gene, systemic inflammation, macrocytic anemia, cytopenias, and bone marrow vacuolization and frequently overlaps with Sweet\u2019s syndrome, relapsing polychondritis, and myelodysplastic syndrome (MDS). Because treatment options are evolving, we reviewed the current and latest evidence of clinical features and therapeutic methods. Methods: A comprehensive literature review was conducted using PubMed and MEDLINE for studies published between 1 January 2020 and 1 July 2025. Search terms included \u201cVEXAS\u201d and \u201ctreatment.\u201d Eligible publications comprised clinical trials, multicenter and observational studies, and case reports containing therapeutic data. Findings were analyzed narratively with emphasis on treatment response, steroid-sparing effects, survival outcomes, and molecular responses. Results: Glucocorticoids remain the first-line therapy for acute management; however, this comes with near-universal steroid dependence. DMARDs and TNF-\u03b1 inhibitors showed limited benefits. IL-6 inhibitors and JAK inhibitors showed improvement in overall response, with JAK inhibitors demonstrating a superior effect. Ruxolitinib showed a higher complete response rate and transfusion independence compared to other JAK inhibitors. Hypomethylating agents, particularly azacitidine, improved hematologic responses in patients with co-existing MDS and reduced UBA1 variant allele burden. Allogeneic hematopoietic stem cell transplantation may be the only current curative method, though with notable transplant-related mortality. Conclusions: JAK inhibitors and hypomethylating agents offer promising disease-modifying potential, while transplant may provide curative intent in selected patients. Ongoing clinical trials are taking place to dictate the treatment direction of VEXAS syndrome.<\/jats:p>","DOI":"10.3390\/hematolrep18030030","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T17:04:59Z","timestamp":1776963899000},"page":"30","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["VEXAS Syndrome: Clinical Features, Hematologic Involvement, and Clinical Outcomes of Current and Emerging Therapies"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5135-7347","authenticated-orcid":false,"given":"Chanika","family":"Assavarittirong","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Southwest Healthcare Medical Education Consortium, Temecula, CA 92590, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Grant","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology, Moores Cancer Center, UC San Diego School of Medicine, UC San Diego Health, San Diego, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep S.","family":"Nayak","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Yale New Haven Health Bridgeport Hospital, Bridgeport, CT 06610, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony L.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Division of Hematology and Cellular Therapy, Moores Cancer Center, UC San Diego School of Medicine, UC San Diego Health, San Diego, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.reuma.2023.10.006","article-title":"VEXAS syndrome: Clinical manifestations, diagnosis, and treatment","volume":"20","author":"Ferrada","year":"2024","journal-title":"Reumatol. Clin. (Engl. Ed.)"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1080\/1744666X.2023.2157262","article-title":"An update on VEXAS syndrome","volume":"19","author":"Savic","year":"2023","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1056\/NEJMoa2026834","article-title":"Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease","volume":"383","author":"Beck","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e775","DOI":"10.1097\/HS9.0000000000000775","article-title":"UBA1 Screening in Sweet Syndrome with Hematological Neoplasms Reveals a Novel Association Between VEXAS and Chronic Myelomonocytic Leukemia","volume":"6","author":"Gurnari","year":"2022","journal-title":"HemaSphere"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1182\/blood.2022016985","article-title":"Translation of cytoplasmic UBA1 contributes to VEXAS syndrome pathogenesis","volume":"140","author":"Ferrada","year":"2022","journal-title":"Blood"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1001\/jama.2022.24836","article-title":"Estimated Prevalence and Clinical Manifestations of UBA1 Variants Associated with VEXAS Syndrome in a Clinical Population","volume":"329","author":"Beck","year":"2023","journal-title":"JAMA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s12185-024-03799-9","article-title":"VEXAS syndrome","volume":"122","author":"Nakajima","year":"2025","journal-title":"Int. J. Hematol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1136\/ard-2023-224460","article-title":"Spanish cohort of VEXAS syndrome: Clinical manifestations, outcome of treatments and novel evidences about UBA1 mosaicism","volume":"82","author":"Mascaro","year":"2023","journal-title":"Ann. Rheum. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1053\/j.seminhematol.2021.10.007","article-title":"Characteristic bone marrow findings in patients with UBA1 somatic mutations and VEXAS syndrome","volume":"58","author":"Patel","year":"2021","journal-title":"Semin. Hematol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3203","DOI":"10.1182\/bloodadvances.2021004976","article-title":"Benign and malignant hematologic manifestations in patients with VEXAS syndrome due to somatic mutations in UBA1","volume":"5","author":"Obiorah","year":"2021","journal-title":"Blood Adv."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"644","DOI":"10.18632\/oncotarget.28646","article-title":"UBA1 dysfunction in VEXAS and cancer","volume":"15","author":"Sakuma","year":"2024","journal-title":"Oncotarget"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1002\/ajh.26931","article-title":"Peripheral blood cells vacuoles in VEXAS syndrome","volume":"98","author":"Tosato","year":"2023","journal-title":"Am. J. Hematol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.3324\/haematol.2021.280238","article-title":"VEXAS syndrome in a female patient with constitutional 45,X (Turner syndrome)","volume":"107","author":"Stubbins","year":"2022","journal-title":"Haematologica"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e402","DOI":"10.1093\/rheumatology\/keab392","article-title":"VEXAS syndrome in a woman","volume":"60","author":"Barba","year":"2021","journal-title":"Rheumatology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"107245","DOI":"10.1016\/j.rmed.2023.107245","article-title":"Pulmonary manifestations in VEXAS syndrome","volume":"213","author":"Baqir","year":"2023","journal-title":"Respir. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1001\/jamadermatol.2024.1657","article-title":"Skin Manifestations of VEXAS Syndrome and Associated Genotypes","volume":"160","author":"Tan","year":"2024","journal-title":"JAMA Dermatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s00415-025-12902-x","article-title":"Neurological manifestations in patients with VEXAS syndrome","volume":"272","author":"Fortanier","year":"2025","journal-title":"J. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1007\/s00415-025-13239-1","article-title":"VEXAS syndrome-associated tumefactive demyelination","volume":"272","author":"Eatz","year":"2025","journal-title":"J. Neurol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e2450251","DOI":"10.1001\/jamanetworkopen.2024.50251","article-title":"Nonischemic Cardiac Manifestations in VEXAS Syndrome","volume":"7","author":"Robert","year":"2024","journal-title":"JAMA Netw. Open"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3747","DOI":"10.1093\/rheumatology\/keaf094","article-title":"VEXAS syndrome through a rheumatologist\u2019s lens: Insights from a Spanish national cohort","volume":"64","author":"Dorta","year":"2025","journal-title":"Rheumatology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2739","DOI":"10.1038\/s41375-022-01698-8","article-title":"A Phase II prospective trial of azacitidine in steroid-dependent or refractory systemic autoimmune\/inflammatory disorders and VEXAS syndrome associated with MDS and CMML","volume":"36","author":"Mekinian","year":"2022","journal-title":"Leukemia"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3431","DOI":"10.3324\/haematol.2024.285519","article-title":"De-escalation of corticosteroids and clonal remission in UBA1 mutation-driven VEXAS syndrome with 5-azacytidine","volume":"109","author":"Trikha","year":"2024","journal-title":"Haematologica"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1111\/bjh.18488","article-title":"Allogeneic haematopoietic stem cell transplantation for VEXAS syndrome: UK experience","volume":"199","author":"Poulter","year":"2022","journal-title":"Br. J. Haematol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1182\/bloodadvances.2023012478","article-title":"Allogeneic hematopoietic cell transplantation for VEXAS syndrome: Results of a multicenter study of the EBMT","volume":"8","author":"Gurnari","year":"2024","journal-title":"Blood Adv."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"E28","DOI":"10.1002\/ajh.26786","article-title":"Reduced intensity conditioning allogeneic hematopoietic stem cell transplantation in VEXAS syndrome: Data from a prospective series of patients","volume":"98","author":"Mangaonkar","year":"2023","journal-title":"Am. J. Hematol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1182\/blood.2022016642","article-title":"Ruxolitinib is more effective than other JAK inhibitors to treat VEXAS syndrome: A retrospective multicenter study","volume":"140","author":"Heiblig","year":"2022","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1136\/ard-2024-225640","article-title":"Efficacy and safety of targeted therapies in VEXAS syndrome: Retrospective study from the FRENVEX","volume":"83","author":"Hadjadj","year":"2024","journal-title":"Ann. Rheum. Dis."},{"key":"ref_28","unstructured":"National Cancer Institute (NCI) (2026, February 10). A Phase II Study of Allogeneic Hematopoietic Stem Cell Transplant for Subjects with VEXAS (Vacuoles, E1 Enzyme, X-Linked, Autoinflammatory, Somatic) Syndrome. Clinical Trial Registration NCT05027945, Available online: https:\/\/clinicaltrials.gov\/study\/NCT05027945."},{"key":"ref_29","unstructured":"Groupe Francophone des Myelodysplasies (2026, February 10). A Single-Arm Phase II with Safety-Run-in Multicenter Study of Momelotinib in Patients with VEXAS Syndrome with or Without Associated Myelodysplastic Syndrome. Clinical Trial Registration NCT07098936, Available online: https:\/\/clinicaltrials.gov\/study\/NCT07098936."},{"key":"ref_30","unstructured":"Swedish Orphan Biovitrum (2026, February 10). PAXIS: A Randomized, Double-Blind, Placebo-Controlled Dose-Finding Phase 2 Study (Part 1) Followed by an Open-Label Period (Part 2) to Assess the Efficacy and Safety of Pacritinib in Patients with VEXAS Syndrome. Clinical Trial Registration NCT06782373, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06782373."},{"key":"ref_31","unstructured":"Washington University School of Medicine (2026, February 10). A Phase 1 Study of Pacritinib in Vacuoles, E1 Ubiqutin-Activating Enzyme, X-Linked, Autoinflammatory, Somatic (VEXAS) Syndrome. Clinical Trial Registration NCT06538181, Available online: https:\/\/clinicaltrials.gov\/study\/NCT06538181."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1111\/bjh.19979","article-title":"JAK2 is a critical therapeutic target in VEXAS syndrome treated with ruxolitinib","volume":"206","author":"Ceccardi","year":"2025","journal-title":"Br. J. Haematol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1177\/15353702231165030","article-title":"JAK inhibitors for the treatment of VEXAS syndrome","volume":"248","author":"Bindoli","year":"2023","journal-title":"Exp. Biol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1111\/bjh.17893","article-title":"Azacitidine for patients with Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome (VEXAS) and myelodysplastic syndrome: Data from the French VEXAS registry","volume":"196","author":"Comont","year":"2022","journal-title":"Br. J. Haematol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1002\/art.43287","article-title":"American College of Rheumatology Guidance Statement for Diagnosis and Management of VEXAS Developed by the International VEXAS Working Group Expert Panel","volume":"78","author":"Mekinian","year":"2026","journal-title":"Arthritis Rheumatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"9127126","DOI":"10.1155\/drp\/9127126","article-title":"JAK Inhibitors for Treatment of VEXAS Syndrome: A Systematic Review of 186 Cases","volume":"2025","author":"Bahramian","year":"2025","journal-title":"Dermatol. Res. Pract."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1182\/blood.2025029732","article-title":"Azacitidine as therapy for VEXAS syndrome","volume":"146","author":"Steensma","year":"2025","journal-title":"Blood"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"4427","DOI":"10.1007\/s00277-024-05942-2","article-title":"Role of allogeneic hematopoietic cell transplantation in VEXAS syndrome","volume":"103","author":"Dias","year":"2024","journal-title":"Ann. Hematol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1136\/ard-2023-224819","article-title":"Serious infections in patients with VEXAS syndrome: Data from the French VEXAS registry","volume":"83","author":"Delaune","year":"2024","journal-title":"Ann. Rheum. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2617","DOI":"10.1007\/s00277-025-06382-2","article-title":"Emerging treatment approaches for VEXAS syndrome: A systematic review and meta-analysis","volume":"104","author":"Kilic","year":"2025","journal-title":"Ann. Hematol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3565","DOI":"10.1007\/s10067-024-07160-7","article-title":"Allogenic haematopoietic stem cell transplantation in VEXAS: A review of 33 patients","volume":"43","author":"Ali","year":"2024","journal-title":"Clin. Rheumatol."}],"container-title":["Hematology Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2038-8330\/18\/3\/30\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T17:25:20Z","timestamp":1776965120000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2038-8330\/18\/3\/30"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,23]]},"references-count":41,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["hematolrep18030030"],"URL":"https:\/\/doi.org\/10.3390\/hematolrep18030030","relation":{},"ISSN":["2038-8330"],"issn-type":[{"value":"2038-8330","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,23]]}}}