Background: Rituximab (RTX) is one of the preferred initial treatment options for patients living with warm autoimmune hemolytic anemia (wAIHA), a clinical subtype of autoimmune hemolytic anemia (AIHA) characterized by the presence of autoantibodies that react optimally at body temperature (37oC). Recommended RTX dosing in wAIHA is cyclical, with patients receiving either four weekly doses of 375 mg/m2 or two doses of 1000 mg on day 1 and 15, with consideration for initiating a new cycle after subsequent treatment relapse (Jäger et al. Blood 2020). Recommended treatment options after relapse are limited. The real-world utilization of RTX and treatment outcomes, including relapse events, after RTX initiation have not been well established among a US patient population.

Objective: To describe treatment patterns and relapse events among wAIHA patients receiving RTX.

Methods: A retrospective cohort study using HealthVerity data from January 2019 to June 2023 was conducted. Individuals were included as wAIHA patients if they had ≥1 claim with a wAIHA diagnosis code (International Classification of Diseases, 10th Revision, Clinical Modification [ICD-10-CM]: D59.11) in the primary position during an inpatient visit, ≥2 claims with D59.11 ≥30 days apart, or ≥1 claim with D59.11 plus one AIHA diagnosis code (ICD-10-CM D59.1x) ≥30 days apart. The date of the earliest AIHA diagnosis code was defined as the diagnosis date. Included patients were aged ≥18 years on the diagnosis date and had ≥12 months' continuous enrollment before and after diagnosis. Patients were excluded if they had ≥2 claims with diagnosis codes for cold or mixed type AIHA (ICD-10-CM: D59.12 or D59.13) ≥30 days apart during the study period. Patients receiving ≥1 RTX infusion post wAIHA diagnosis were classified as RTX users, and the date of the first infusion was classified as the index date. Post-index analyses included a description of RTX treatment cycles and relapse episodes. Relapse episodes were characterized by a composite of relapse events including initiation of a new RTX cycle, blood transfusion, splenectomy, erythropoiesis stimulating agent administration, immunoglobulin administration, or a hospitalization with an AIHA code in the primary billing position. Relapse events occurring within 30 days of the previous event were counted as part of the same episode, and a gap of at least 30 days between RTX doses was used to define the start of a new RTX cycle. Summary statistics of continuous variables and the count and frequency of categorical variables were calculated.

Results: Among the 1,309 wAIHA patients identified, 380 (29.0%) received at least one administration of RTX during a mean (standard deviation [SD]) follow up of 24.2 (8.0) months post-diagnosis. 274 (72.1%) RTX-treated patients received only one cycle of RTX, and 106 (27.9%) received ≥2 cycles. At diagnosis, the mean (SD) age of the RTX-treated patients was 51.5 (17.8) years, 60.5% of patients were female, and the mean (SD) Quan-Charlson comorbidity index score was 2.6 (2.4). After the index RTX dose, patients were followed for a mean (SD) of 20.6 (8.6) months. Patients received a mean (SD) of 2.4 (1.5) doses of RTX per cycle. Among the 106 patients who received more than one cycle of RTX, patients received a mean (SD) of 2.5 (1.9) doses of RTX per cycle, with 16 (15.1%) patients receiving >4 doses for at least 1 cycle. During post-index follow up, 197 (51.8%) patients experienced at least 1 relapse episode. 80 (21.1%) RTX-treated patients experienced at least 1 relapse episode within 6 months after the index date, and 122 (32.1%) RTX-treated patients experienced at least 1 relapse within 12 months after index. 70 (18.4%) RTX-treated patients experienced at least 1 wAIHA-related hospitalization during follow up, and 220 wAIHA-related hospitalizations were observed in total. 40 (10.5%) RTX-treated patients received a total of 69 blood transfusions.

Conclusions: Given the high relapse frequency observed within this study, a considerable burden remains among wAIHA patients initiating RTX. Relapses were largely characterized by wAIHA hospitalizations and blood transfusions, both suggestive of clinically meaningful hemolysis among many patients within this cohort. RTX dosing patterns were variable, with many patients receiving more than 4 administrations per cycle. An unmet need remains for improved control of wAIHA, particularly among patients experiencing relapses after RTX initiation.

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2025
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