{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:58:21Z","timestamp":1786978701939,"version":"build-2736575974"},"reference-count":30,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sobi Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>VEXAS (Vacuoles, E1 ubiquitin-activating enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a systemic disorder characterized by an overlap of hematologic and inflammatory features. Most patients require chronic use of moderate-to-high doses of glucocorticoids (GCs) to maintain disease control. Data on GC-sparing therapies is limited, and there have been no prospective pharmacotherapeutic trials in VEXAS syndrome published to date. Pacritinib, an oral inhibitor of IRAK1, JAK2, and ACVR1, has emerged as a promising therapeutic option for VEXAS syndrome. The PAXIS trial is the first prospective, randomized pharmacotherapeutic study conducted in this rare and severe disease. Utilizing a novel study design and disease-specific endpoints, the trial will evaluate the efficacy and safety of two dose levels of pacritinib compared with placebo in patients with VEXAS syndrome (NCT06782373, EUCTR: 2024-516347-41-00).<\/jats:p>","DOI":"10.3390\/jcm15041426","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T17:45:36Z","timestamp":1770831936000},"page":"1426","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["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"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5884-6231","authenticated-orcid":false,"given":"David B.","family":"Beck","sequence":"first","affiliation":[{"name":"Center for Human Genetics and Genomics, 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Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1111\/bjd.20805","article-title":"Further characterization of clinical and laboratory features in VEXAS syndrome: Large-scale analysis of a multicentre case series of 116 French patients","volume":"186","author":"Terrier","year":"2022","journal-title":"Br. J. Dermatol."},{"key":"ref_3","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. 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Arthritis Rheumatol., Epub ahead of printing.","DOI":"10.1002\/art.43287"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/S0140-6736(25)02164-6","article-title":"VEXAS syndrome: A comprehensive review of pathogenesis, clinical spectrum, and therapeutic strategies","volume":"407","author":"Groarke","year":"2026","journal-title":"Lancet"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1038\/s41467-024-44811-4","article-title":"VEXAS syndrome is characterized by inflammasome activation and monocyte dysregulation","volume":"15","author":"Kosmider","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4690","DOI":"10.1038\/s41467-025-59890-0","article-title":"In depth transcriptomic profiling defines a landscape of dysfunctional immune responses in patients with VEXAS syndrome","volume":"16","author":"Mizumaki","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e193011","DOI":"10.1172\/JCI193011","article-title":"UBA1-depleted neutrophils disrupt immune homeostasis and induce VEXAS-like autoinflammatory disease in mice","volume":"135","author":"Dong","year":"2025","journal-title":"J. Clin. Investig."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1038\/s41591-025-03623-9","article-title":"Mechanisms of hematopoietic clonal dominance in VEXAS syndrome","volume":"31","author":"Molteni","year":"2025","journal-title":"Nat. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1182\/blood.2024028216","article-title":"Impaired cytotoxic function and exhausted phenotype of natural killer cells in VEXAS syndrome","volume":"146","author":"Breillat","year":"2025","journal-title":"Blood"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Smith, J.A. (2018). Regulation of cytokine production by the unfolded protein response; implications for infection and autoimmunity. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00422"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3872","DOI":"10.1093\/rheumatology\/keae530","article-title":"Low remission rates and high incidence of adverse events in a prospective VEXAS syndrome registry","volume":"64","author":"Kirino","year":"2025","journal-title":"Rheumatology"},{"key":"ref_16","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."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2653","DOI":"10.1016\/j.mayocp.2021.06.006","article-title":"Clinical heterogeneity of the VEXAS syndrome: A case series","volume":"96","author":"Koster","year":"2021","journal-title":"Mayo Clin. Proc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1517\/14740338.2016.1140743","article-title":"Long-term side effects of glucocorticoids","volume":"15","author":"Oray","year":"2016","journal-title":"Expert Opin. Drug. Saf."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"152010","DOI":"10.1016\/j.semarthrit.2022.152010","article-title":"The glucocorticoid toxicity index: Measuring change in glucocorticoid toxicity over time","volume":"55","author":"Stone","year":"2022","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1002\/acr.22722","article-title":"Prednisone use and risk of mortality in patients with rheumatoid arthritis: Moderation by use of disease-modifying antirheumatic drugs","volume":"68","author":"Wasko","year":"2016","journal-title":"Arthritis Care Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1002\/art.38210","article-title":"Glucocorticoid dose thresholds associated with all-cause and cardiovascular mortality in rheumatoid arthritis","volume":"66","author":"Battafarano","year":"2014","journal-title":"Arthritis Rheumatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3682","DOI":"10.1182\/blood.2020010177","article-title":"Therapeutic options in VEXAS syndrome: Insights from a retrospective series","volume":"137","author":"Bourbon","year":"2021","journal-title":"Blood"},{"key":"ref_23","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_24","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1136\/annrheumdis-2021-220876","article-title":"Tocilizumab in VEXAS relapsing polychondritis: A single-center pilot study in Japan","volume":"80","author":"Kirino","year":"2021","journal-title":"Ann. Rheum. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"11","DOI":"10.2147\/JEP.S110702","article-title":"Comprehensive kinase profile of pacritinib, a nonmyelosuppressive Janus kinase 2 inhibitor","volume":"8","author":"Singer","year":"2016","journal-title":"J. Exp. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5835","DOI":"10.1182\/bloodadvances.2023010151","article-title":"Pacritinib is a potent ACVR1 inhibitor with significant anemia benefit in patients with myelofibrosis","volume":"7","author":"Oh","year":"2023","journal-title":"Blood Adv."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"eaap8112","DOI":"10.1126\/scisignal.aap8112","article-title":"Interleukin-2 shapes the cytotoxic T cell proteome and immune environment-sensing programs","volume":"11","author":"Rollings","year":"2018","journal-title":"Sci. Signal."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Singer, J.W., Al-Fayoumi, S., Taylor, J., Velichko, S., and O\u2019Mahony, A. (2019). Comparative phenotypic profiling of the JAK2 inhibitors ruxolitinib, fedratinib, momelotinib, and pacritinib reveals distinct mechanistic signatures. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0222944"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Weeks, L.D., Hammond, D., Savic, S., Heiblig, M., Chowdhury, O., Mekinian, A., Gurnari, C., Ramchandren, R., Georgin-Lavialle, S., and Ferrada, M.A. (2025). Establishing a consensus definition of VEXAS flare for clinical research. Rheumatology, Epub ahead of printing.","DOI":"10.1093\/rheumatology\/keaf624"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.ard.2025.05.767","article-title":"Development of a disease activity index for the assessment of VEXAS syndrome (VEXAS-DAI)","volume":"84","author":"Byram","year":"2025","journal-title":"Ann. Rheum. Dis."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/4\/1426\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T10:28:22Z","timestamp":1770892102000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/4\/1426"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,11]]},"references-count":30,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["jcm15041426"],"URL":"https:\/\/doi.org\/10.3390\/jcm15041426","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,11]]}}}