Study finds JAK inhibitors and tocilizumab effective in VEXAS syndrome

A recent study presented at ACR Convergence 2023 has offered newfound hope for individuals battling VEXAS syndrome, a rare and often lethal autoimmune disorder resulting from a UBA1 gene mutation. The research demonstrates the superior effectiveness of JAK inhibitors (JAKi) and tocilizumab in managing VEXAS syndrome, in stark comparison to other targeted therapies.

VEXAS syndrome is a debilitating condition characterized by extensive inflammation affecting the skin, lungs, blood vessels, and joints. Typically, high-dose corticosteroids are employed in its management, but these treatments come with severe side effects and limited supporting data. Alarmingly, the five-year survival rate for VEXAS patients is strikingly low.

The study enrolled a predominantly male patient cohort from the French national VEXAS registry, spanning from November 2020 to August 2023. All patients had received at least one targeted therapy, with a significant portion undergoing JAKi ruxolitinib or the interleukin (IL)-6 inhibitor tocilizumab.

After three months, the findings revealed an overall response rate of 24% for JAK inhibitors, 32% for IL-6 inhibitors, 9% for IL-1 inhibitors, and 0% for TNF blockers and other targeted medications. At six months, the overall response rate for JAK inhibitors slightly increased to 30%, while IL-6 drugs dipped to 26%. Notably, the numbers of complete and partial responses were similar, and the withdrawal of corticosteroids exhibited comparable patterns.

A more pronounced contrast arose concerning treatment discontinuation during follow-up: 28% for JAKi (with a median delay of 7.2 months) versus 69% for IL-6 inhibitors (with a median delay of 5.1 months). Although serious side effects were almost double with IL-6 inhibitors, there were fewer fatalities compared to JAKi. This underscores the instrumental role of JAK inhibitors and tocilizumab in revolutionizing VEXAS syndrome treatment.

Reference: AMERICAN COLLEGE OF RHEUMATOLOGY