Can treatments for autoimmune diseases cause neoplastic changes?
Long-term use of azathioprine, an anti-proliferative immunosuppressant antimetabolite, is associated with a seven-fold risk in the development of acute myeloid leukaemia or myelodysplastic syndrome, according to a recent US study.
Long term use of azathioprine, an anti-proliferative immunosuppressant antimetabolite, is associated with a seven-fold risk in the development of myeloid malignancy (acute myeloid leukaemia) or myeloid tumours (myelodysplastic syndrome), according to a recent US study.
In this retrospective case control study, researchers examined the association of various therapies used in the treatment of more common autoimmune diseases, including rheumatoid arthritis, psoriasis, and systemic lupus erythematosus, with the risk of neoplastic changes.
The medical records of about 40,000 patients living with autoimmune disease who attended the Mayo Clinic in Phoenix, Arizona were examined from more than a decade of treatment. The researchers compared a variety of data – including disease type, drug exposure and duration of cytotoxic, anti-inflammatory and other disease-modulating medications – with the data of patients without bone marrow disorder. Drugs studied in the analysis included azathioprine and cytotoxic chemotherapies such as cyclophosphamide, mitoxantrone, methotrexate and mercaptopurine.
The study identified 86 patients with therapy-related myeloid neoplasm, with 55 developing myelodysplastic syndrome, 21 de novo acute myeloid leukaemia and 10 who developed acute myeloid leukaemia after a history of myelodysplastic syndrome. The median length of time from the onset of the autoimmune disease to the formation or presence of abnormal growth was eight years.
There was no significant association between the extent of exposure to the treatment and the class of agent. Other agents were also examined, such as anti-tumour necrosis factor agents. However, only azathioprine was associated with a statistically significant increased risk of life-threatening magnitude.
Ertz-Archambault N, Kosiorek H, Taylor G et al (2017). Association of therapy for autoimmune disease with myelodysplastic syndromes and acute myeloid leukemia. JAMA Oncology doi:10.1001/jamaoncol.2016.6345