A Phase II prospective trial of azacitidine in steroid-dependent or refractory systemic autoimmune/inflammatory disorders and VEXAS syndrome associated with MDS and CMML

Mékinian, A.; Zhao, Lin; Chevret, Sylvie; Desseaux, Kristell; Pascal, Laurent; Comont, Thibaut; Maria, A.; Péterlin, Pierre; Terriou, Louis; Piney, Maud D’Aveni; Gourin, Marie-Pierre; Vey, Norbert; Rauzy, Odile Beyne; Grobost, Vincent; Bézanahary, H.; Dimicoli‐Salazar, Sophie; Banos, Anne; Wickenhauser, Stefan; Renzis, Benoît de; Durot, Éric; Natarajan-Amé, Shanti; Voillat, Laurent; Chermat, Fatiha; Lemaire, Karine; Jachiet, Vincent; Himberlin, Chantal; Thépot, Sylvain; Diaz, José Miguel Torregrosa; Frenzel, Laurent; Gyan, Emmanuel; Denis, Guillaume; Hirsch, Pierre; Kosmider, Olivier; Adès, Lionel; Fain, Olivier; Fenaux, Pierre

doi:10.1038/s41375-022-01698-8

Cited by 59 publications

(89 citation statements)

References 15 publications

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“…All 5 primary studies [14][15][16][17][18] were non-randomized studies. Four of the studies [14][15][16][17] were retrospective cohort studies; 3 of these [15][16][17] were uncontrolled (i.e., single-arm cohort studies), and the fourth 14 included within-patient comparisons (i.e., the same patient may have received multiple lines of therapy) between outcomes associated with ruxolitinib, tocilizumab, and azacitidine, compared with corticosteroids.…”

Section: Methodsmentioning

confidence: 99%

“…Four of the studies [14][15][16][17] were retrospective cohort studies; 3 of these [15][16][17] were uncontrolled (i.e., single-arm cohort studies), and the fourth 14 included within-patient comparisons (i.e., the same patient may have received multiple lines of therapy) between outcomes associated with ruxolitinib, tocilizumab, and azacitidine, compared with corticosteroids. The fifth study 18 was a single-arm prospective clinical trial, in which the diagnosis of VEXAS was made retrospectively because the UBA1 mutation associated with VEXAS was discovered after the trial had been started.…”

Section: Methodsmentioning

confidence: 99%

“…In 1 study, 15 the study eligibility criteria aligned with the current report, while in the other 4 studies, 14,[16][17][18] the eligibility criteria were broader, yet the data were summarized for relevant subgroups.…”

Section: Methodsmentioning

confidence: 99%

“…All 5 studies [14][15][16][17][18] were published in 2021 14 or 2022, [15][16][17][18] with study periods ranging from July 2017 18 to February 2022 16 (where reported).…”

Section: Methodsmentioning

confidence: 99%

“…The characteristics of the 5 primary studies [14][15][16][17][18] are summarized in the subsequent sections, and additional details are provided in Appendix 2.…”

Section: Summary Of Study Characteristicsmentioning

confidence: 99%

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Treatment Options for VEXAS Syndrome

Goring¹,

Horton²

2022

cjht

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VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a disorder caused by a genetic mutation, and is characterized by hematologic and autoinflammatory symptoms that are severe and progressive. It is typically seen in older men and is considered to be rare. Proposed treatments for VEXAS syndrome include DNA hypomethylating agents such as azacitidine, anti-IL6 monoclonal antibodies such as tocilizumab, and Janus kinase inhibitors such as ruxolitinib. We found 5 non-randomized studies on the effectiveness of the proposed treatments — 4 on azacitidine; 1 on ruxolitinib; and 1 on azacitidine, ruxolitinib, and tocilizumab. There are several limitations to the research studies, most notably that they included a small number of patients who were retrospectively identified as having VEXAS syndrome. Therefore, the effectiveness of tocilizumab, ruxolitinib, and azacitidine for treating VEXAS syndrome is uncertain. We did not find any evidence-based guidelines on the management of VEXAS syndrome.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…All 5 studies [14][15][16][17][18] were published in 2021 14 or 2022, [15][16][17][18] with study periods ranging from July 2017 18 to February 2022 16 (where reported).…”

Section: Methodsmentioning

confidence: 99%

“…The characteristics of the 5 primary studies [14][15][16][17][18] are summarized in the subsequent sections, and additional details are provided in Appendix 2.…”

Section: Summary Of Study Characteristicsmentioning

confidence: 99%

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Treatment Options for VEXAS Syndrome

Goring¹,

Horton²

2022

cjht

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VEXAS syndrome: Clinical, hematologic features and a practical approach to diagnosis and management

Koster,

Lasho,

Olteanu

et al. 2023

American J Hematol

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VEXAS (Vacuoles, E1 enzyme, X‐linked, Autoinflammatory, Somatic) syndrome is a newly identified disease caused by somatic alterations in UBA1 which produce a recalcitrant inflammatory state along with hematologic disturbances. Patients with VEXAS can have a wide spectrum of clinical symptoms and providers should be familiar with the heterogeneity of associated clinical features. While hematologic parameters may be generally non‐specific, peripheral blood features of macrocytosis, monocytopenia, and/or thrombocytopenia coupled with bone marrow vacuolization of erythroid or myeloid precursors should raise suspicion for this condition. Due to an increased mortality, prompt recognition and accurate diagnosis is paramount. Access to testing for confirmation of UBA1 variants is not yet universally available but clinicians should understand the current available options for genetic confirmation of this disease. Treatment options are limited due to lack of prospective clinical trials but cytokine directed therapies such as interleukin‐6 inhibitors and JAK–STAT inhibitors as well as hypomethylating agents such as azacitidine have shown evidence of partial effect. Though cases are limited, allogeneic stem cell transplantation holds promise for durable response and potential cure. The intent of this review is to outline the pathophysiology of VEXAS syndrome and to provide a practical approach to diagnosis and treatment.

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