Real‐World Use of Rituximab in the Treatment of Cold Agglutinin Disease in the United States: A Retrospective Study

Introduction: Rituximab is used off-label for treating cold agglutinin disease (CAD) in the United States; however, real-world data on its use are limited. Methods: This study examined (1) treatment patterns, (2) prespecified safety outcomes, and (3) changes in hemolytic markers post rituximab infusion (threshold change from baseline: hemoglobin [Hb]: ≥2 g/dL increase; bilirubin or lactate dehydrogenase [LDH]: ≥50% decrease). Of 611 patients with CAD (Cohort 1) identified using Optum's de-identified Market Clarity database (2007-2021), 94 who received rituximab (Cohort 2) were included. Results: Rituximab was predominantly used as monotherapy; the median (interquartile range; IQR) number of rituximab courses per patient was 1.0 (1.0-2.0); 24 (25.5%) patients had ≥1 incomplete course and 37 (39.4%) required blood transfusion. The incidence rate (IR) of serious infections per 1000 patient-years (95% CI) post rituximab initiation was three times higher than before rituximab initiation (637.1 [242.2-1032.0] vs. 245.4 [125.1-365.6]). Cohort 2 had a similar IR of thromboembolic events and slightly higher hospitalization rates and deaths than Cohort 1. After the first course of rituximab, 69.5% (41/59), 59.6% (28/47), and 31.3% (10/32) of patients reached thresholds for Hb, bilirubin, and LDH, respectively. The median (IQR) duration of improvement was 44 (13.3-90.8), 98 (29.0-257.0), and 93 (21.3-161.8) days for Hb, bilirubin, and LDH, respectively. Reversal from threshold occurred in 68.3% (28/41), 53.6% (15/28), and 80.0% (8/10) of patients for Hb, bilirubin, and LDH, respectively. Conclusion: Rituximab showed a limited durability of response and an increased risk of infection, suggesting the need for more effective and safer treatment options. : The authors have confirmed clinical trial registration is not needed for this submission.