Autoimmune Disease Treatments May Increase Risk of Myeloid Neoplasm
Azathioprine exposure linked to myeloid neoplasm.
A drug commonly used to treat autoimmune diseases may increase the risk of myeloid neoplasm.
Across the clinical landscape, myeloid neoplasms associated with treatments for autoimmune disease is becoming an emerging phenomenon.
In a study published in JAMA Oncology, investigators sought to determine the association between the risk of developing myeloid neoplasm and the use of cytotoxic, anti-inflammatory, and immunomodulating agents that treat autoimmune diseases.
Included in the retrospective, multicenter, case-control study and medical record review were 40,011 patients with primary autoimmune diseases—–such as lupus and rheumatoid arthritis––who were observed at 2 centers from January 1, 2004, to December 31, 2014.
Of the 40,011 participants, 311 had a concomitant coded diagnosis of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Eighty-six cases met the inclusion criteria, and the case-control match was performed at a 2:1 ratio.
In total, 57 of 86 cases received a cytotoxic or immunomodulating agent. In the comparison group of 172 controls, 105 received either agent.
The results of the study showed that exposure to the autoimmune drug azathioprine was associated with a 7-fold risk for myeloid neoplasm. The control and case cohorts had similar systemic exposures by agent category, the investigators noted. There was no association found for anti-tumor necrosis factor agents.
“This study, along with our current knowledge of therapy-related myeloid neoplasm, suggests that individualized drug selection and monitoring during treatment could be possible,” said co-author Natalie Ertz-Archambault, MD.
The findings indicated that only azathioprine showed a statistically significant association with an increased risk of therapy-related myeloid neoplasm. However, other agents demonstrated a similar trend, but it was not statistically significant.
“Similar associations were already documented in case reports and case series, but have never been evaluated in a broad spectrum of autoimmune diseases in that many patients and in context of individual medications,” said senior author Raoul Tibes, MD, PhD. “Interestingly, there was no association with length of time on therapy and resulting myeloid neoplasm.
“Future genomic profiling studies may help to identify patients at risk for myeloid neoplasms when exposed to azathioprine of other drugs.”
Limitations to the study were that it was a retrospective study; many different autoimmune diseases were analyzed; only MDS and AML were assessed; no definitive casual association was made between taking a particular drug and MDS or AML; and the number of patients with autoimmune disease who develop MDS or AML is still low overall.
Although the findings are of interest, the authors stress that they should not change or replace clinical judgements, monitoring, and current standard treatments in patients with autoimmune disease.
In the next phase of the study, the investigators plan to perform molecular investigations into the genetic susceptibility for treatment-related myeloid neoplasm.