An observational analysis of disease burden in patients with cold agglutinin disease: Results from a large US electronic health record database.

Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia (AIHA). Information regarding the impact of CAD from the patient and health care system perspective is limited. To understand longitudinal trends in outcomes in patients with CAD, including anemia severity, hemolytic status, administration of CAD-related therapies, and health care resource utilization (HCRU). This retrospective, observational cohort study used data from the US Optum Electronic Health Record database. Included patients were aged 18 years and older at the index date (first CAD mention in physician"s notes), had 1 or more medical encounters with an AIHA-related diagnosis code during the study period, and had 3 or more CAD mentions during the patient identification period (January 2008 to March 2019). The baseline period was the 12 months preceding the index date. Anemia severity (severe, hemoglobin < 8.0 g/dL; moderate, 8.0-10.0 g/dL; mild, 10.1-11.9 g/dL; no anemia, ≥ 12.0 g/dL) and hemolytic status (elevated lactate dehydrogenase [LDH; > 250 μ/L] and/or elevated bilirubin [> 1.2 mg/dL]) were assessed at baseline and 6-monthly followup intervals. Use of CAD-related therapies, blood transfusions, and all-cause HCRU were analyzed every 6 months; results were stratified by anemia severity. The analysis included 610 adults with CAD (median [interquartile range; IQR] age 72.0 [61.0-78.0] years; 65.4% female). Median (IQR) duration of follow-up was 42.8 (22.8-68.4) months. The proportion of patients with moderate/severe anemia was 51.0% at baseline, 57.7% over 12 months' follow-up, and 66.6% over full follow-up. During the full follow-up period, approximately 50% of patients had elevated bilirubin and LDH levels. Corticosteroids were the most frequently used medication (65.6% of patients) over full follow-up. Mean (SD) number of blood transfusions per patient was 3.26 (9.21) over 12 months and 5.47 (17.11) over the full follow-up. At full follow-up, 68.7% of patients with severe anemia received a transfusion vs 12.6% and 0.0% with moderate or mild anemia, respectively. At 12 months, 34.1%, 97.7%, and 29.3% of patients had 1 or more hospitalizations, outpatient services, or emergency department visits (full follow-up: 52.5%, 99.0%, and 53.9%), respectively. Across all time periods, HCRU was greater in patients with severe anemia vs mild or moderate anemia. CAD imposed a substantial long-term burden on patients and health care systems, and despite the use of several therapies, hemolysis and anemia still occurred. The use of CAD-related therapies and HCRU was generally greater with greater anemia severity. These results suggest a lack of effective treatment options available for patients with CAD at the time of this analysis. This study was sponsored by Sanofi. Dr Wilson, Dr Joly, Mr Carita, and Ms Miles are employees and stockholders of Sanofi. Dr Adeyemi was an employee and may have held stocks at Sanofi at the time of the study. Ms Miles and Ms Kuang were employees of Aetion Inc at the time of this study; Aetion Inc is a software company that received funding from Sanofi for the current study. Dr Pham is a consultant for Sanofi and Argenx.