TOPLINE: 

Canakinumab, an interleukin-1 inhibitor, yielded significantly higher clinical response rates, longer drug survival, and fewer adverse events than anakinra in male patients with vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome.

METHODOLOGY:

• Researchers conducted a retrospective study using data from French and Israeli registries and an Italian center to compare the efficacy, drug survival, and safety of two interleukin-1 inhibitors, anakinra and canakinumab, in patients with VEXAS syndrome.
• They included 47 male patients with VEXAS syndrome (mean age, 72 years): 44 received anakinra (100 mg/d), nine received canakinumab (150 or 300 mg/mo), and six received both drugs at different timepoints.
• The primary outcome was global response, defined as the sum of complete response (absence of inflammatory symptoms, prednisone dose < 10 mg/d or equivalent, and C-reactive protein [CRP] level ≤ 10 mg/L) and partial response (absence of inflammatory symptoms with ≤ 50% reduction in CRP levels and prednisone doses).
• Drug survival and adverse events were also assessed.

TAKEAWAY:

• Canakinumab yielded a significantly higher rate of global response than anakinra at 1 month (100% vs 34%; P < .001) and 3 months (78% vs 22%; P = .001).
• At 3 months, treatment with canakinumab was associated with higher odds of achieving global response (adjusted odds ratio, 28.78; P = .004).
• Patients treated with canakinumab had significantly longer median drug survival than those treated with anakinra (15 months vs 1 month; P = .006). The risk for treatment withdrawal was higher with anakinra compared with 300-mg canakinumab (hazard ratio, 6.27; P = .013).
• Adverse events were more frequent in the anakinra group than in the canakinumab group (P = .028), with injection-site reactions occurring only in the anakinra group.

IN PRACTICE:

"When considering financial factors, IL1i [interleukin-1 inhibitor] for VEXAS patients may be used sequentially, with canakinumab regarded as a rescue therapy for patients who do not tolerate anakinra. Specifically, canakinumab at 300 mg/month may be considered an additional steroid-sparing therapeutic option for VEXAS patients, alongside ruxolitinib, tocilizumab, and azacitidine," the authors wrote.

SOURCE:

This study was led by Tali Eviatar, MD, Tel Aviv Medical Center and Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel. It was published online on September 22, 2025, in Arthritis & Rheumatology.

LIMITATIONS:

The lack of full independence between treatment groups may have affected the analysis, as six patients received both anakinra and canakinumab one after the other. The groups were not randomly assigned, and patients were treated on the basis of local practices. The small sample size of the canakinumab group may have led to unstable estimates. 

DISCLOSURES:

This research received no specific funding. Some authors reported receiving honoraria, consulting fees, and/or support for attending meetings or serving as advisors for various pharmaceutical companies, including AbbVie, AstraZeneca, and Novartis. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.