JAK, IL-6 inhibitors outperform other targeted therapies for VEXAS syndrome
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SAN DIEGO — Janus kinase and interleukin-6 inhibitors are superior to other targeted agents as a first-line therapy for VEXAS syndrome, according to data presented at ACR Convergence 2023.
“Only described 3 years ago, VEXAS syndrome is an autoimmune disease mainly affecting men over 50 years, due to an acquired somatic mutation in the UBA1 gene in hematopoietic stem cell,” Jerome Hadjadj, MD, PhD, an internist at Assistance Publique-Hôpitaux de Paris, said during a press conference. “Due to the recent description of the disease, there are no guidelines to treat these patients, with some data [coming] from very small retrospective studies. Before 3 years ago, many patients did not even have a clear diagnosis [and now] there are different ways to treat these patients all over the world.”
To assess the efficacy and safety of targeted therapies among patients with VEXAS syndrome, Hadjadj and colleagues examined patient data from the national French VEXAS registry from November 2020 to August 2023. The researchers included a total of 110 patients who demonstrated genetically proven VEXAS syndrome who had been administered at least one targeted therapy.
The majority of patients in the cohort had been prescribed either the JAK inhibitor ruxolitinib (Jakafi, Incyte) or the IL-6 inhibitor tocilizumab (Actemra, Genentech), with 40% and 26%, respectively, receiving these drugs. Other assessed targeted therapies included the IL-1 inhibitor anakinra (Kineret, Swedish Orphan Biovitrum) (17%), TNF inhibitors (10%) and additional targeted agents (6%). Hadjadj and colleagues noted that 48% of patients in the cohort had received more than one targeted therapy.
The researchers defined complete response to treatment as clinical remission with a CRP of less than 10 mg/L and daily corticosteroid doses of less than 10 mg, whereas partial response was defined as clinical remission with a 50% reduction in CRP and corticosteroids.
According to study results, overall response at 3 months was highest for IL-6 inhibitors (32%) and JAK inhibitors (24%), compared with IL-1 inhibitors (9%), TNF inhibitors and other targeted therapies (0%). At 6 months, the overall response rate for JAK inhibitors had increased marginally to 30%, while the IL-6 response rate had dropped to 26%.
The researchers observed that compared with JAK inhibitors, other targeted therapies exhibited a significantly higher risk for treatment withdrawal. Treatment was discontinued in 28% of patients who received JAK inhibitors, compared with 69% of patients who received IL-6 inhibitors. However, the researchers noted that serious adverse events were significantly higher for IL-6 inhibitors compared with JAK inhibitors — 31% vs. 19%. Additionally, there were more deaths associated with JAK inhibitors than IL-6 — 19% vs. 9%.
“In terms of clinical response, both ruxolitinib and tocilizumab are similar, but in general, we still think that ruxolitinib is superior to tocilizumab,” Hadjadj said. “[However,] tocilizumab could be a good alternative to ruxolitinib in the case of older adults, and those with cytopenia or infections.
“We think that all the other targeted therapies, such as anti-TNF and anti-IL-1, should not be used as the first-line treatment for VEXAS syndrome,” he added. “At present, we are trying to design a randomized prospective study to compare tocilizumab and ruxolitinib, and I hope we will present this data in a future Congress.”
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Hadjadj J, et al. Abstract L03. Presented at: ACR Convergence 2023; Nov. 10-15, 2023; San Diego.
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