Jackson, Louis

Abstract Background: Autoimmune hemolytic anemia (AIHA) is a condition in which the immune system erroneously attacks and damages red blood cells. While the epidemiology of AIHA has been examined in various European and Asian nations (Hansen 2020; Kao 2025), there is limited data available from the United States (US). Using US insurance claims data, this research aimed to determine the prevalence and demographic characteristics of AIHA over a five-year span. Methods: Five databases were used: Merative MarketScan Commercial Claims and Encounters; Optum's de-identified Clinformatics® Data Mart Database; Closed and Open claims sourced through HealthVerity; Merative MarketScan Medicare Supplemental Database; Merative MarketScan Multi-State Medicaid. AIHA was defined by ICD-10 diagnosis codes D59.1x in a given calendar year and a second code within 365 days prior. Annual prevalence in years 2019 – 2023 was calculated among people with insurance enrollment for at least 6 months in the calendar year. Annual prevalence was stratified by age group, sex, and prescription fill for an AIHA-related treatment (systemic steroids, immunosuppressants [azathioprine, mycophenolate, cyclosporin, cyclophosphamide, danazol, bortezomib, rituximab], splenectomy) in the calendar year. Extrapolation of prevalence rates for commercial and government assistance insurance to the US population for 2023 was implemented by age and sex-standardization to the US Census population. For data sources that included both commercial and government assistance insurance, patients aged <65 years were analyzed as commercial insurance and aged ≥65 years as government assistance. Results: AIHA prevalence in 2023 across databases ranged from 2.7 to 4.3 per 100,000 for ages <18 years; 4.2 to 9.4 per 100,000 for ages 18 – 34 years; 8.2 to 11.8 per 100,000 for ages 35 – 49 years; 15.4 to 23.9 per 100,000 for ages 50 – 64 years; 26.6 to 37.0 per 100,000 for ages 65 – 74 years; and 30.6 to 61.2 per 100,000 for age 75 years and older. Across databases and over time, the proportion of AIHA patients that were female was 55% – 67%. Across all databases, in year 2023, half (44% - 55%) of patients received any AIHA-related treatment, out of which one third (26%-34%) received systemic steroids, less than one quarter (9% – 17%) received rituximab, and one third (25% – 31%) received a different immunosuppressant. Compared to patients with commercial insurance, Medicaid-insured patients had lower AIHA-related treatment utilization, whereas Medicare-insured patients had higher utilization. Within age group and sex and by insurance type, low and high estimates of prevalence were used to define a range of prevalence. After standardization to the 2023 US Census population, the estimated prevalence in 2023 ranged from 38,459 to 57,235 patients diagnosed with AIHA, corresponding to prevalence rates of 11.6 to 17.3 per 100,000. This marked an increase from 2019 US Census-standardized estimates of 32,777 to 48,482, with corresponding prevalence rates of 10.1 to 14.9 per 100,000. Discussion: AIHA prevalence was higher in older age groups, with a peak prevalence in ages 65 and older. Prevalence increased approximately 15% over a 5-year interval and was notably higher in patients with commercial health insurance compared to government insurance programs, which may in part be due to the older age of the Medicare population. Fewer than half of patients received an AIHA-related treatment in 2023, which could reflect heterogeneity in disease severity necessitating treatment, in addition to the relapse-remitting nature of AIHA whereby patients experience remission for periods of time. Additionally, insurance claims do not specify an indication for treatment nor a reason for discontinuation; some treatments could have been prescribed for an underlying condition contributing to AIHA. Finally, prevalence extrapolation assumes Americans without health insurance are diagnosed with AIHA at the same rate as those with insurance, which may slightly overestimate the total number of diagnosed patients.Conclusion: AIHA prevalence in this study was consistent with estimates from European countries and has been increasing in recent years, providing evidence of consistent disease epidemiology across several geographies.

Abstract INTRODUCTION: Warm autoimmune hemolytic anemia (wAIHA) is a rare, autoimmune-mediated hematologic disorder associated with significant morbidity and mortality and may occur as a primary condition or secondary to an underlying disorder. It is the most common subtype of autoimmune hemolytic anemia (AIHA), accounting for 75-80% of AIHA cases. Older adults with wAIHA are particularly vulnerable, as they often have multiple comorbidities and are already at elevated risk of death. This study aimed to assess mortality associated with wAIHA. METHODS: Adults with wAIHA (wAIHA cohort) and without AIHA (non-AIHA cohort) were identified from the 100% Medicare Fee-for-Service database (10/01/2019–12/31/2023). Evidence of wAIHA was defined as one of the following: 1) a primary wAIHA diagnosis (International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM]: D59.11) in the inpatient setting (first instance of wAIHA diagnosis defined the index date), 2) ≥2 wAIHA diagnosis in any setting ≥30 days apart (second instance of wAIHA diagnosis defined the index date), or 3) a wAIHA diagnosis preceded ≥30 days by any AIHA diagnosis (ICD-10-CM: D59.10, D59.19, D59.8, D59.9; first instance of wAIHA diagnosis defined the index date). Patients in the wAIHA cohort were excluded if they had a diagnosis for cold or mixed-type AIHA (ICD-10-CM: D59.12, D59.13) during the baseline period (12 months before index). The non-AIHA cohort had no diagnoses for any AIHA during the study period; a random index date during continuous Medicare eligibility was selected and patients were matched 1:10 with the wAIHA cohort based on age on index date. Using overlap weighting, age-matched cohorts were further weighted on sex, race, region, index year, and baseline comorbidities associated with mortality, excluding conditions defining secondary wAIHA. Mortality during the follow-up period was evaluated between the weighted cohorts using the Kaplan-Meier method and Cox proportional hazard models. Patients whose death was not observed were censored at the earlier of the end of continuous Medicare eligibility or data availability. RESULTS: 3,112 and 31,120 patients were included in the wAIHA and non-AIHA cohorts, respectively. After weighting, among the wAIHA vs non-AIHA cohorts, mean [standard deviation; SD] age was 74.4 [11.6] vs 74.6 [11.2] years, the proportion of female were 56.1% vs 56.1%, mean [SD] Quan-CCI without secondary wAIHA-defining conditions was 1.9 [2.0] vs 1.9 [2.1], and mean [SD] follow-up time was 17.2 [11.7] vs 14.9 [11.4] months, respectively. In addition, 53.7% of the wAIHA cohort had secondary wAIHA. The most common secondary wAIHA-defining conditions were autoimmune and inflammatory diseases (wAIHA cohort: 27.8%; non-AIHA cohort: 11.0%), hematologic and lymphoproliferative disorders (wAIHA cohort: 23.8%; non-AIHA cohort: 1.3%), and solid tumors (wAIHA cohort: 16.8%; non-AIHA cohort: 12.6%). The most common comorbidities for both cohorts were hypertension (wAIHA cohort: 77.4%; non-AIHA cohort: 78.3%) and dyslipidemia (wAIHA cohort: 72.2%; non-AIHA cohort: 74.7%). Survival rates in the wAIHA and non-AIHA cohorts were 80.3% vs 84.0% at 12 months, 70.7% vs 77.6% at 24 months, and 63.7% vs 73.1% at 36 months, respectively (all p<0.001). Patients with wAIHA were at 20%, 27%, and 30% higher risk of death at 12, 24, and 36 months, respectively, compared to patients without AIHA (hazard ratios: 1.20, 1.27, and 1.30; all p<0.001). CONCLUSIONS: This large retrospective study is the first to assess real-world incremental mortality associated with wAIHA among Medicare beneficiaries. Patients with wAIHA were at significantly greater risk of death following the initial diagnosis. These results may point to potential gaps in early diagnosis and effective disease management, which could contribute to increased mortality. Future research should focus on specific subgroups within the wAIHA cohort to identify differences in mortality as well as characteristics that may be associated with death.

Abstract BackgroundWarm autoimmune hemolytic anemia (wAIHA) is clinically characterized by autoantibody-mediated (typically IgG) erythrocyte destruction at body temperature. While oral corticosteroids remain first-line therapy, rituximab is frequently used as a second-line agent, mostly supported with concomitant background medications, yet real-world evidence is limited and utilization is driven by published retrospective data and expert opinion. Real-world evidence characterizing its utilization patterns and outcomes is needed to inform clinical practice. AimsThis study aimed to: 1) describe treatment patterns among patients with newly diagnosed wAIHA, 2) evaluate rescue therapy use and healthcare resource utilization (HCRU) with current standard of care (SOC), 3) characterize patterns of rituximab use during the first year. MethodsNewly diagnosed wAIHA patients were identified from multiple US databases (MarketScan® Databases, IQVIA PharMetrics, Optum Clinformatics®, and Optum PanTher EHR). Patients with ≥1 wAIHA diagnosis code in any position (ICD-10-CM D59.11) from October 2020 to December 2023 and 12-month post-index follow-up were pooled together. Secondary wAIHA was defined with evidence of hematologic malignancy, solid tumors, immunodeficiencies, or autoimmune diseases in the 6 months prior to diagnosis. Patients on treatment were defined by use of oral corticosteroids (OCS), immunosuppressants (IST) (including azathioprine, mycophenolate mofetil, cyclosporine, cyclophosphamide, or tacrolimus) or rituximab. Initial therapy was defined as the first treatment occurring ≥ 30 days prior to diagnosis. Therapies were identified as combination when initialized within 21 days of each other. The regimen is considered active until all therapies are discontinued or a new agent is initiated. Rituximab regimens were classified as standard (4 weekly doses), alternative (2 doses given 2 weeks apart), single infusion, or extended (>4 infusions). Results Among 2,028 wAIHA patients (median age 62.0 years, 59% female), 55% had secondary wAIHA. Among patients on treatment (n=1,439), 64% received OCS monotherapy; rituximab and IST, alone or in combination with OCS were received by an additional 28% and 5% of patients, respectively. Overall, 80% of treated patients received OCS in some combination during initial therapy. Within 12 months following diagnosis, 1 in 4 patients required ≥ 1 blood transfusion, 1 in 8 required either erythropoiesis-stimulating agents (ESA) or intravenous immunoglobulin (IVIG). Within 12 months of diagnosis, 35% of patients required ≥ 1 hospitalization, average length of stay 3.8 days; AIHA was the principal diagnosis for 65% cases. Greater than 1/3 of patients (38%) had ≥ 1 emergency department visit. Almost all wAIHA patients (98%) had an all-cause outpatient visit with a median of 31 visits per patient. Among patients receiving rituximab in any line (n=613), median time from diagnosis to first administration was 59.0 days (interquartile range: 42.0-171.0). For the first course of rituximab, 62.2% of patients received a complete course (standard, alternative, or extended courses). Among patients with a completed course, 39.8% had >4 infusions without a 90-day gap between administrations with a median of 8 administrations within 12 months. Of the nearly 38% of patients that did not receive a complete course of rituximab, 33% received a single infusion. The use of rescue medications in the period prior to rituximab treatment was compared to the period after treatment (defined as 60 days to 12-months post final rituximab infusion). Use of blood transfusions was observed to increase from 9.0% to 32.8%, while the use of ESA and IVIG were stable at approximately 2% and 4%, respectively.Conclusion With current wAIHA SOC, US HCRU remains high, posing a financial burden in terms of the rate of outpatient and emergency department visits, and inpatient stays. Rituximab is an early line therapy post-diagnosis, typically in combination with OCS. No changes in rescue treatments, and an increase in blood transfusions after rituximab infusion suggest treatment gaps remain. Analysis reveals heterogeneity in rituximab dosing patterns including high deviation from standard dosing practices; this variance from published expert opinion along with common use of rescue therapies suggests continued need for standardized guidelines and development of targeted therapies in wAIHA.