How to treat VEXAS syndrome: a systematic review on effectiveness and safety of current treatment strategies

Abstract

Objectives To evaluate the effectiveness and safety of current treatment strategies for the vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. Methods A protocolized systematic review according to PRISMA guidelines was performed. Three databases were searched for reports on treatment strategies for VEXAS. Data from the included publications was extracted and a narrative synthesis was performed. Treatment response was recorded as complete (CR), partial (PR) or none (NR) depending on changes in clinical symptoms and laboratory parameters. Patient characteristics, safety data and previous treatments were analyzed. Results We identified 36 publications with a total of 116 patients, 113 (98.3%) were male. The identified reports included azacytidine (CR 9/36, 25%; PR 14/36, 38.9%), JAK inhibitors (CR 11/33, 33%; PR 9/33, 27.3%), tocilizumab (CR 3/15, 20%; PR 6/15, 40%), allogeneic stem cell transplantation (alloSCT) (CR 6/7, 85.7%; one patient died), anakinra (CR 4/5, 80%; NR 1/5, 20%), canakinumab (CR ½, 50%; PR ½, 50%) and glucocorticoid monotherapy (CR 1/6, 16.7%; PR 4/6, 66.7%). Individual reports were available for TNF-inhibitors, rituximab, and methotrexate. Data on adverse events were available for 67 patients (67/116, 57.8%) and included: pneumonia (12/67, 17.9%), other infections (9/67, 13.4%), venous thromboembolisms (VTE) (6/67, 8.9%), cytopenias (4/67, 6.7%), acute (4/67, 5.9%) and chronic graft-versus-host-disease (2/67, 2.9%). Conclusion Current data on VEXAS treatment are limited and inhomogeneous. Treatment decisions should be individualized. For the devolvement of treatment algorithms clinical trials are needed. AEs remain a challenge, especially an elevated risk for venous thromboembolism associated to JAKi treatment should be carefully considered.

Fever, Rash, and Shortness of Breath in a 69-Year-Old

“…2 The diagnosis of VEXAS syndrome is made by identifying UBA1 gene variants with polymerase chain reaction-based sequencing of DNA extracted from peripheral blood, bone marrow, or formalin-fixed paraffin-embedded tissue in a patient with symptoms characteristic of VEXAS syndrome. 7,8 In the absence of rigorous trials, corticosteroids are typically first-line treatment. Trials of steroid-sparing agents such as tocilizumab, azacitidine, Janus kinase (JAK) inhibitors, and allogeneic stem cell transplant have included very small numbers of patients and have produced variable results with high rates of adverse events (eg, pneumonia, thromboembolism).…”

“…9,10 Patients diagnosed with VEXAS syndrome have a 5-year survival of approximately 63%, 6 and those with the p.Met41Val variant had a median survival of 9 years after symptom onset. 8…”

“…On bone marrow biopsy, more than 10% cytoplasmic vacuoles in myeloid and erythroid precursor cells is an indication for UB1A testing . The diagnosis of VEXAS syndrome is made by identifying UBA1 gene variants with polymerase chain reaction–based sequencing of DNA extracted from peripheral blood, bone marrow, or formalin-fixed paraffin-embedded tissue in a patient with symptoms characteristic of VEXAS syndrome …”

VEXAS‐Syndrom, eine neu beschriebene autoinflammatorische Systemerkrankung mit dermatologischen Manifestationen

“…Therapeutisch sind in der Regel hohe Glukokortikosteroiddosen zur Krankheitskontrolle erforderlich, wobei es beim Ausschleichen oft zu Rezidiven kommt. Verschiedene immunmodulierende Systemtherapeutika (DMARDs, disease modifying antirheumatic drugs ) wurden zur Therapie des VEXAS‐Syndroms mit mäßigem Erfolg eingesetzt; 30 erfolgreichere Therapieverläufe wurden mit Interleukin‐1‐Rezeptorantagonisten (Anakinra), 8,13 Anti‐Interleukin‐1β‐Antikörpern (Canakinumab), 31 (auch in Kombination mit Ciclosporin), 32 dem Interleukin‐6‐Rezeptorantagonisten Tocilizumab, 33–35 dem Anti‐IL‐6‐Antikörper Siltuximab 29 und Januskinase (JAK)‐Inhibitoren beschrieben. In einer retrospektiven Analyse von 30 am VEXAS‐Syndrom erkrankten Patienten, die mit JAK‐Inhibitoren behandelt wurden, erwies sich Ruxolitinib als der effektivste.…”

A novel XNA-based Luminex assay to detect UBA1 somatic mutations associated with VEXAS syndrome

“…Patients often show clinical manifestations of fever, extreme fatigue, chondritis, pulmonary infiltrates, cytopenia, vasculitis and neutrophilic dermatosis. Moreover, on many occasions patients with VEXAS present strong association with hematologic malignancy including myelodysplastic syndrome (MDS) and multiple myeloma [ 2 ].…”