Azathioprine linked to increased myeloid neoplasm risk
medwireNews: Azathioprine sodium exposure in patients with autoimmune disorders is associated with an elevated risk of developing myeloid neoplasms, shows a chart review published in JAMA Oncology.
“Therapy-related myeloid neoplasms are a potentially life-threatening consequence of treatment for autoimmune disease,” explain the researchers who examined the relationship between different classes of systemic agents and the risk for myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).
Of 40,011 individuals diagnosed with an autoimmune disorder at one of two US centers during a 10-year period, 86 developed MDS or AML no earlier than a month after the initial diagnosis, and were matched by age, gender, and autoimmune condition to 172 controls without myeloid neoplasms.
During a median follow-up of 21.6 months, the overall use of cytotoxic agents did not vary between cases and controls, but azathioprine was used significantly more often by patients who did versus did not develop myeloid neoplasms, at an odds ratio (OR) of 7.05. The association remained significant in a multivariate analysis adjusting for other cytotoxic agents (OR=6.92).
Cyclophosphamide and mitoxantrone use was more frequent in cases than controls, whereas methotrexate sodium, mercaptopurine, and mycophenolate mofetil hydrochloride were used less frequently by cases. But the associations did not reach statistical significance, which the authors attribute to the small sample sizes of the individual drug subgroups.
Raoul Tibes, from the Mayo Clinic in Phoenix, Arizona, and collaborators note that exposure to immunomodulating agents, including tumor necrosis factor (TNF) blockers, anti-inflammatory drugs or corticosteroids, was not associated with an increased risk of myeloid neoplasm formation in the study population.
Given the “documented risk for lymphoma” with TNF inhibitor treatment, they believe their finding is “very important,” but admit the need for confirmation in other datasets.
Tibes et al write that the results “are expected to contribute to knowledge of therapy-related myeloid malignant neoplasms in patients treated for [autoimmune disease], suggesting that individualized drug selection and monitoring during treatment could become possible, especially for patients requiring treatment with azathioprine and cytotoxic agents.”
But they add: “Although our results are intriguing, they should at this stage not change or replace the clinical judgments, monitoring, and current standard treatments or interventions in [autoimmune disease].”
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