New research presented at the annual meeting of the American College of Rheumatology (ACR) has revealed that JAK inhibitors (JAKi) and tocilizumab have demonstrated higher response rates in the treatment of VEXAS syndrome compared to other targeted therapies. VEXAS syndrome is a rare autoimmune condition caused by a mutation in the UBA1 gene, resulting in widespread inflammation and various symptoms affecting the skin, lungs, blood vessels, and joints.
Previously, VEXAS syndrome was primarily managed with high doses of corticosteroids, which come with significant side effects and limited evidence supporting their effectiveness. To explore alternative treatments, researchers conducted a multicenter retrospective study involving 110 predominantly male patients from the French national VEXAS registry. The patients had received various targeted therapies, with the majority receiving JAK inhibitors or tocilizumab. Other therapies included IL-1 inhibitors and TNF blockers.
The study measured the response to treatment at three and six months, defining complete response as clinical remission with CRP levels less than 10 mg/L and reduced corticosteroid use. Partial response was indicated by clinical remission with a 50% reduction in CRP and corticosteroids. The results showed that at three months, JAK inhibitors achieved an overall response rate of 24%, while IL-6 inhibitors, particularly tocilizumab, had a response rate of 32%. In contrast, IL-1 inhibitors had a response rate of 9%, and TNF blockers and other targeted drugs had no response. By six months, JAK inhibitors maintained a response rate of 30%, while IL-6 inhibitors slightly decreased to 26%.
Additionally, the study revealed that JAK inhibitors had a significantly lower rate of treatment discontinuation during follow-up compared to IL-6 inhibitors. The main reasons for discontinuation were treatment failure, severe side effects, or death. Serious side effects were more common with IL-6 inhibitors, although the number of deaths was lower compared to JAK inhibitors.
Lead author Jerome Hadjadj emphasized the surprising nature of the results, as previous studies in France had highlighted the efficacy of JAK inhibitors as a first-line therapy for VEXAS syndrome. Based on their findings, Hadjadj suggests that tocilizumab could be a viable alternative, while other drugs showed limited effectiveness. He also highlighted that JAK inhibitors demonstrated longer survival without treatment withdrawal, primarily due to serious adverse events associated with other targeted therapies.
The study does have limitations, including its retrospective nature and the use of various targeted therapies by patients, which could introduce biases. Nevertheless, the results present valuable insights for clinicians and pave the way for future prospective studies to improve the treatment of VEXAS syndrome.
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
