Real-World Adherence and Persistence to Emicizumab Using a National US Claims Database

Introduction: Emicizumab is the first bispecific factor IXa- and factor X-directed antibody approved in the US for routine prophylaxis in adult and pediatric people with hemophilia A (PwHA) with or without factor VIII (FVIII) inhibitors. Relative to FVIII-based prophylaxis given 2 or 3 times a week to people with severe HA, emicizumab can be self-administered subcutaneously and dosed every week, every 2 weeks or every 4 weeks. This may translate to higher real-world adherence rates relative to the recently reported adherence rate of 65.2% for intravenously administered FVIII therapies based on clinical chart information and dispensing pharmacy records. Adherence to prophylaxis is important for PwHA and can potentially lead to better bleed control and consequently lower long-term joint problems. The few studies that have evaluated real-world adherence and persistence to emicizumab have included limited sample sizes. This study describes real-world adherence and persistence to emicizumab prophylaxis among a US population of PwHA.

Methods: This retrospective observational cohort study uses adjudicated health plan claims data from IQVIA PharMetrics Plus. PwHA were included if they had ≥1 International Statistical Classification of Diseases, Tenth Revision (ICD-10) diagnosis code for HA during the study period (5/1/2017 to 9/30/2023), ≥2 emicizumab fills ≥2 days apart during the study period and continuous medical and pharmacy benefits for ≥6 months prior and 12 months after the initial emicizumab fill date (index date). PwHA were excluded if they had any ICD-10 diagnosis codes for hemophilia B or other bleeding disorders. Days’ supply was imputed for claims with the days’ supply field missing. Adherence was calculated using the proportion of days covered (PDC) during the 12-month period after the index date. PwHA were considered adherent if they met the PDC ≥80% threshold. Persistence was calculated as the proportion of PwHA continuing emicizumab within 12 months of the index date, where discontinuation was defined as a treatment gap of ≥60 days. Among adherent PwHA, we also evaluated concomitant utilization of FVIII during the 12 months after the index date. Descriptive statistics were used to summarize results.

Results: Among 280 PwHA included in the study, the average (SD) age was 26 (16) years, and most were male (98%). During the 6-month preindex period, 51% of PwHA had ≥1 FVIII claim, and 1.4% had ≥1 claim for a bypassing agent. We estimated that 85% of PwHA (n=237) were persistent with emicizumab therapy over the 12-month period. The median PDC was 92%, with 76% of PwHA (n=213) achieving a PDC rate ≥80%. Adherence and persistence rates were lowest in the 19- to 30-year and ≥51-year age groups as well as in the Northeast region. Among the 213 PwHA who were adherent, less than half (43%) received any FVIII during the 12-month postindex period, with a mean (SD) number of FVIII claims of 1.14 (2.04). The mean (SD) number of days with an FVIII claim during the postindex period was 0.79 (1.20) and ranged from 0 to 5 days. Study limitations include those commonly associated with the use of claims data (claims data only capture medications that were dispensed and do not indicate whether the individual took the medication as intended, potential misclassification bias due to the presence of a diagnosis code on a medical claim not always being positive for the presence of disease or use of over-the-counter medications). Furthermore, the dataset mostly included PwHA enrolled in a commercial health plan; thus, these results may not be generalizable to US PwHA who are enrolled in noncommercial insurance plans or uninsured. Lastly, for the evaluation of FVIII claims, some PwHA may have had FVIII available on hand that was previously filled before initiating emicizumab.

Conclusions: Real-world adherence to emicizumab as measured by claims data continues to be high, with low discontinuation rates. On average, adherent PwHA have 1 FVIII claim during the 12 months after emicizumab initiation. These results complement and are consistent with previous studies for emicizumab.