Ruxolitinib is more effective than other JAK inhibitors to treat VEXAS syndrome: a retrospective multicenter study

Heiblig, Maël; Ferrada, Marcela; Koster, Matthew J.; Barba, Thomas; Gerfaud‐Valentin, Mathieu; Mékinian, A.; Coelho, Henrique; Fossard, Gaëlle; Barraco, Fiorenza; Galicier, Lionel; Bienvenu, Boris; Hirsch, Pierre; Vial, Guillaume; Boutin, Anne-Blandine; Galland, J.; Guenno, G. Le; Bigot, A.; Warrington, Kenneth J.; Kermani, Tanaz A.; Grayson, Peter C.; Patel, Bhavisha; Beck, David B.; Jamilloux, Yvan; Fenaux, Pierre; Sujobert, Pierre

doi:10.1182/blood.2022016642

Cited by 116 publications

(126 citation statements)

References 12 publications

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“…In patients who fail colchicine and anti-IL-1 therapy, JAKi are increasingly used in a similar, empirical fashion. 142 …”

Section: Discussionmentioning

confidence: 99%

“…In patients who fail colchicine and anti-IL-1 therapy, JAKi are increasingly used in a similar, empirical fashion. 142 Recent discovery of VEXAS syndrome provides a paradigm shift in thinking around the role of somatic mutations in the disease pathogenesis other than malignancy. The role of such acquired process in the development of many more common disorders is just starting to be fully appreciated.…”

Section: Discussionmentioning

confidence: 99%

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Improving Diagnosis and Clinical Management of Acquired Systemic Autoinflammatory Diseases

Al‐Hakim¹,

Mistry²,

Savic³

2022

JIR

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Systemic autoinflammatory diseases (SAID) are conditions caused by dysregulation or disturbance of the innate immune system, with neutrophils and macrophages the main effector cells. Although there are now more than 40 distinct, genetically defined SAIDs, the genetic/molecular diagnosis remains unknown for a significant proportion of patients with the disease onset in adulthood. This review focuses on new developments related to acquired/late onset SAID, including phenocopies of monogenic disorders, Schnitzler’s syndrome, Adult onset Still’s disease, VEXAS syndrome, and autoinflammatory complications associated with myelodysplastic syndrome.

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“…In patients who fail colchicine and anti-IL-1 therapy, JAKi are increasingly used in a similar, empirical fashion. 142 …”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Improving Diagnosis and Clinical Management of Acquired Systemic Autoinflammatory Diseases

Al‐Hakim¹,

Mistry²,

Savic³

2022

JIR

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“…One hypothesis raised is that the gain in efficacy of ruxolitinib compared to other inhibitors is related to the target specificity of ruxolitinib, with an inhibitory action essentially of JAK1, JAK2. However, these treatments do not allow the eradication of the UBA1 clone, since the UBA1 clone is still visible by sequencing on the follow-up samples [ 18 ].…”

Section: Vexas Syndromementioning

confidence: 99%

“…They also propose that one solution may be to inhibit cellular stress pathways such as the UPR pathway that are frequently activated in IAD [ 7 ]. The disappearance of the UBA1 clone at molecular sequencing after the introduction of a new therapeutic line would indeed be a good argument for the effectiveness of the treatment [ 18 ].…”

Section: Vexas Syndromementioning

confidence: 99%

VEXAS Syndrome: A Novelty in MDS Landscape

Templé

Kosmider

2022

Diagnostics

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Fever, inflammation and vacuoles in hematopoietic cells represent the main features associated with VEXAS syndrome, a new prototype of autoinflammatory disorders genetically characterized by somatic mutation of the UBA1 gene which encodes the enzyme1-activating enzyme (E1) required for ubiquitin signaling. Described very recently, patients with VEXAS syndrome present a systemic autoinflammatory syndrome associated with hematological impairments, especially cytopenias whose pathophysiology is mainly non-elucidated. Initially diagnosed in elderly male patients, VEXAS syndrome was frequently associated with a diagnosis of myelodysplastic syndromes (MDS) leading the medical community to first consider VEXAS syndrome as a new subtype of MDS. However, since the first description of VEXAS patients in 2021, it appears from the multitude of case reports that MDS associated with VEXAS are different from the classically described MDS.

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“…B. Interleukin-1-, Interleukin-6-oder JAK-Blockade) werden meist hohe Glukokortikoiddosen zur Krankheitskontrolle benötigt. Interessanterweise scheint Ruxolitinib in der antiinflammatorischen Kontrolle besser geeignet zu sein als andere JAK-Inhibitoren [18]. Auch wird der Nutzen einer Kombinationstherapie aus Interleukin-1-Blockade und Ciclosporin beschrieben [19].…”

Section: Therapie Und Prognoseunclassified

Das VEXAS-Syndrom

Krusche¹,

Kötter²

2022

Arthritis und Rheuma

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ZUSAMMENFASSUNGDas VEXAS-Syndrom ist eine neu identifizierte autoinflammatorische Systemerkrankung. Dabei steht das Akronym VEXAS für Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic. Zugrundeliegend für die Erkrankung ist eine somatische Mutation des UBA1-Gens. Dieses kodiert für das E1-Enzym, welches für die Ubiquitinierung von Proteinen verantwortlich ist. Aufgrund der fehlerhaften Ubiquitinierung kommt es zu einer Überregulierung von proinflammatorischen Zytokinen. Da das UBA1-Gen auf dem X-Chromosom liegt, sind von der Erkrankung fast nur Männer betroffen. Interessanterweise tritt das VEXAS-Syndrom erst in der 2. Lebenshälfte auf und die Betroffenen können eine Vielzahl von inflammatorischen klinischen Symptomen aufweisen. Insbesondere das Vorliegen von zytoplasmatischen Vakuolen im Knochenmark ist charakteristisch. Hierbei kommt es in der klinischen Ausprägung häufig zu Überlappungen aus hämatologischen, dermatologischen und rheumatologischen Krankheitsbildern. Der Artikel gibt einen Überblick über die Pathophysiologie, Klinik und Diagnostik des Erkrankungsbildes.

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Ruxolitinib is more effective than other JAK inhibitors to treat VEXAS syndrome: a retrospective multicenter study

Cited by 116 publications

References 12 publications

Improving Diagnosis and Clinical Management of Acquired Systemic Autoinflammatory Diseases

Improving Diagnosis and Clinical Management of Acquired Systemic Autoinflammatory Diseases

VEXAS Syndrome: A Novelty in MDS Landscape

Das VEXAS-Syndrom

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