Background: Anemia can be triggered after ruxolitinib treatment among patients with myelofibrosis (MF). However, the association between anemia developed after ruxolitinib treatment and adverse clinical outcomes related to MF in routine clinical practice is not fully evaluated.

Objective: To assess the risk of all-cause death, cardiovascular disease (CVD) hospitalization, serious infection, and acute myeloid leukemia (AML) among patients with ruxolitinib-related anemia.

Methods: We conducted a nationwide, population-based cohort study using the National Health Insurance Service database (2014–2023) of South Korea. Eligible patients were patients with MF who initiated ruxolitinib and did not have anemia within 180 days prior to ruxolitinib initiation. Anemic status was assessed within 180 days after ruxolitinib initiation, and the index date was defined as the date 180 days after ruxolitinib initiation. The outcomes were all-cause death, CVD hospitalization, serious infection, and AML. Patients were followed from the index date until the earliest of outcome occurrence, all-cause death, hematopoietic stem cell transplantation (HSCT), or the study end date (December 31, 2023). Cox proportional hazard models were used to estimate crude and adjusted hazard ratios (HRs) of the study outcomes; demographic and clinical characteristics were used for adjustments.

Results: Among a total of 687 eligible patients, 350 patients (45.1% older than 70 years; 43.7% male) developed anemia after ruxolitinib treatment while 337 patients (32.9% older than 70 years; 57.0% male) did not. Compared to non-anemic patients, ruxolitinib-related anemia was associated with increased risk of all-cause death (crude HR 1.56, 95% CI, 1.17–2.07), CVD hospitalization (1.44, 1.00–2.06), and serious infection (1.50, 1.21–1.85), but not with AML (0.92, 0.55–1.54). After adjustment, this association was attenuated and became non-significant except serious infection (adjusted HR 1.29 [0.95–1.75] for all-cause death; 1.24 [0.84–1.81] for CVD hospitalization; 1.36 [1.08–1.72] for serious infection).

Conclusion: Ruxolitinib-related anemia may be associated with increased risks of all-cause death, CVD hospitalization, and serious infection. These findings suggest that physicians should consider routine monitoring for CVD or serious infections in patients with MF receiving ruxolitinib according to their anemic status.