Risk of myelodysplastic syndrome and myeloproliferative neoplasms in patients with stable coronary artery disease and autoimmune conditions treated with colchicine.

e18581 Background: Patients with stable coronary artery disease (CAD) and autoimmune diseases (AI) are at increased risk of myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN), driven by chronic inflammation and clonal hematopoiesis. This multicenter cohort study assesses the impact of colchicine on MDS and MPN incidence compared to methotrexate and prednisone in this high-risk population. Methods: We queried TriNetX, an aggregated electronic health record platform to identify adults with stable CAD and AI conditions (Behçet syndrome, gout, Sjögren syndrome, myositis, fibrosclerosis, polymyalgia rheumatica, vasculitis, or calcium pyrophosphate arthritis)—key indications for colchicine use—between January 2015 and January 2024. Exclusion criteria included preexisting MDS, MPN, AML, dialysis, advanced heart failure, recent myocardial infarction, or critical care admissions. Patients with ≥3 prescriptions of colchicine, prednisone, or methotrexate were propensity score-matched for 50 covariates such as age, sex, race, cardiovascular/cardiometabolic comorbidities, personal/family history of neoplasm, occupational exposure, chemotherapy, radiation, percutaneous coronary intervention, smoking/alcohol use, CRP/ESR, and medications (antihypertensives, DAPT, cholesterol medications, antiplatelets) and followed for 120 months. The primary outcome was the incidence of MDS, MPN, or AML; secondary outcomes included major adverse cardiovascular events and overall survival. Kaplan-Meier analysis estimated risk with hazard ratios (HR) and 95% confidence intervals (CI). Results: After 1:1 matching, 68,680 patients were included in the colchicine vs. prednisone analysis (mean age 68.1 ± 12.0 years; 24.7% female; 61.5% White) and 11,856 in the colchicine vs. methotrexate analysis (mean age 66.4 ± 12.0 years; 50.3% female; 67.1% White). Compared to prednisone, colchicine reduced the risk of MDS by 19.5% (HR 0.81, CI 0.69–0.94) and AML by 30.5% (HR 0.70, CI 0.55–0.87). Compared to methotrexate, colchicine reduced MDS risk by 30.5% (HR 0.67, CI 0.50–0.97) and AML risk by 62.7% (HR 0.37, CI 0.26–0.53). No significant differences were observed in MPN risk or cardiovascular event rates or overall survival. Conclusions: Colchicine significantly reduced the risk of MDS and AML compared to prednisone and methotrexate, likely due to its anti-inflammatory effects on clonal hematopoiesis. The lack of impact on MPN suggests distinct mechanisms less driven by inflammation.