Background: VEXAS syndrome is an acquired hemato-autoinflammatory disease affecting adult male patients. It is characterized by macrocytosis, anemia, myelodysplastic syndrome (MDS), and episodes of inflammation. While interleukin-1 inhibition (IL1i) is a cornerstone in the treatment of many autoinflammatory diseases, current data suggest that their use in VEXAS may be associated with severe adverse events, mostly severe skin reactions with anakinra usage. In terms of efficacy, Hadjadj et al. reported that only 9% of 33 patients treated with IL1i achieved a response at 3 months [1]. Data regarding canakinumab use is scarce.

Objectives: To describe the experience with IL1i treatment of VEXAS patients, and compare drug survival, and adverse event rates between anakinra and canakinumab.

Methods: This was a retrospective multicenter cohort study, which included patients from the FRENVEX registry (a multicenter registry of French VEXAS patients), the Israeli VEXAS registry, and Italian patients. Demographic and clinical data, including genetic data, medication use and dose (prednisone, immunosuppressive, biologics and targeted synthetic medications), response to treatment and adverse events were collected anonymously from medical files. Statistical analysis was performed comparing patients treated with canakinumab to those treated with anakinra using descriptive statistics (numbers, percentages, mean±standard deviation (SD). Categorical variables were compared using the Fisher exact test, and numeric variables were compared using student T-test. The primary endpoint was drug survival.

Results: The analysis included 50 male VEXAS patients. Of these, 45 participants received anakinra and 10 received canakinumab (five patients used both drugs at different time points) (Table 1). The groups were similar in regard to age, UBA1 mutations, MDS and clinical inflammatory manifestations. All patients treated with anakinra used 100 mg/day dose, with one patient increasing the dosage to 200 mg/day. In the canakinumab group, five patients were treated with 300 mg/4 weeks, while five received 150mg/4 weeks, with two of them increasing the dosage to 300 mg/4 weeks. Prednisone dose, as well as CRP levels at initiation of IL1i treatment were not statistically different between groups, although numerically mildly higher in the anakinra group. The drug survival of canakinumab was statistically longer than for anakinra (26.1±23.75 vs 6.41±10.4 months, respectively, p<0.001). Drug survival for patients receiving 300 mg or 150 mg of canakinumab was 38.86±23.44 and 5.67±15 months respectively. To date, 93.33% of anakinra treated patients compared to 70% of canakinumab treated patients stopped the medication (p=0.003). The rate of infections was similar between groups (pneumonia*5, c. difficile*2, erysipelas/cellulitis*3, COVID19, salmonella, urosepsis with shock). Local skin reactions were reported in 20/37 patients treated with anakinra but none of the canakinumab patients. Neutropenia was reported in 1/10 and 5/35 patients in the canakinumab and anakinra groups, respectively. Although the reasons for discontinuations were statistically similar between the groups, most patients stopped anakinra due to adverse events, while canakinumab was stopped mostly due to disease flares.

Conclusion: Eventhough VEXAS was first described more than 4 years ago, the best treatment approach remains unknown. Drug survival of canakinumab was higher than that of anakinra – with survival in patients receiving the 300 mg/month dose of more than 3 years on average, while in the 150 mg/month dose and anakinra group – survival was ~6 months. This is probably due to a lower adverse event rate and a higher rate of response in the canakinumab group. Adverse events may be the main restriction for survival of anakinra use in VEXAS patients. Canakinumab 300 mg/month may be considered as another steroid sparing therapeutic option for VEXAS patients, along with ruxolitinib, tocilizumab, and azacitidine.

REFERENCES: [1] Hadjadj J, et al. Ann Rheum Dis . 2024;83:1358–67.

Acknowledgements: NIL.

Disclosure of Interests: Tali Eviatar Abbvie, Novartis, GSK, AstraZeneca, AstraZeneca, GSK, Abbvie, AstraZeneca,GSK, Iftach Sagy: None declared, Corrado Campochiaro: None declared, Valentin Lacombe: None declared, Vincent Jachiet: None declared, Oshrat Tayer Shifman: None declared, David Ozeri: None declared, Alessandro Tomelleri: None declared, Benjamin Terrier: None declared, Hagit Peleg: None declared, Thibault Comont: None declared, Karim Sacre: None declared, Woaye-Hune Pascal: None declared, Laurent Arnaud: None declared, Estibaliz Lazaro: None declared, Vincent Grobost: None declared, François Lifermann: None declared, Maxime Samson: None declared, Samuel Ardois: None declared, Alice Garnier: None declared, Alexandre Maria: None declared, Alain Cantagrel: None declared, Aurore Meyer: None declared, Jean-David Bouaziz: None declared, Mael Heiblig: None declared, Michael Zisapel: None declared, Ori Elkayam: None declared, Jérôme Hadjadj: None declared, Sophie Georgin-Lavialle: None declared, Arsene Mekinian: None declared.

© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.