OBJECTIVES: The aim of the study was to evaluate the treatment response to Interleukin-6-receptor inhibitition (IL-6Ri), primarily tocilizumab, in patients with VEXAS.

METHODS: Data were obtained from review of hospital based clinical records and included symptoms, laboratory data, transfusion history, pathology reports, imaging, and treatment.

RESULTS: Fifteen patients were treated with tocilizumab intravenously. Two patients changed treatment to subcutaneous sarilumab. Three discontinued treatment due to treatment failure.Of the 10 patients with treatment-response and prednisone use prior to IL-6Ri one was tapered off prednisone, one used it intermittently, and seven patients could be reduced to 10 mg or less daily.Three patients exhibited a marked decrease in UBA1-levels during IL-6Ri which corresponded with symptom control and normalization of haemoglobin levels. However, in most a progressive marrow failure occurred as indicated by decreasing platelet levels, increasing MCV, and for some, declining haemoglobin levels and transfusion dependence in spite of control of the inflammatory symptoms and low c-reactive protein levels.One patient became refractory to both tocilizumab and sarilumab, and had previously failed conventional DMARDs, JAK-inhibition, TNFa-inhibition, and interleukin-1R-inhibiton. Treatment with 9 cycles of azacytidine resulted in complete symptom remission, discontinuation of prednisone, normalization of biochemical parameters and undetectable UBA1 mutation levels which has now lasted for 10 months since cessation of azacytidine.

CONCLUSION: IL-6Ri induces control of inflammatory symptoms and allows decreased prednisone usage in a large subset of VEXAS patients. However, most experience progressive bone marrow failure during IL-6Ri.Azacytidine could be a promising treatment strategy and warrants further investigation.