Abstract
Background
The efficacy and safety of emicizumab in preventing bleeds in patients with Hemophilia A has been established through clinical trials and real-world experience. However, certain individuals still experience breakthrough bleeding while on emicizumab and there is currently no guidance on the optimal work up in individuals with persistent breakthrough bleeding or suspected therapy failure. Emicizumab plasma levels have emerged as a possible method of monitoring treatment response and drug activity, but its clinical utility in predicting occurrence of breakthrough bleeds while on emicizumab remains yet to be established. Our study aimed to evaluate the possible correlates of breakthrough bleeding and emicizumab plasma levels among individuals with severe Hemophilia A.
Methods The study was a retrospective study carried out at the Louisiana Center for Bleeding and Clotting Disorders involving all individuals ≥ 12 years with hemophilia A being treated with emicizumab collected from Jan 2019 - July 2025. A total of 36 patients were included in the analysis. Sociodemographic data was collected as well as information on a) medication adherence b) breakthrough bleeding while on emicizumab c) use of factor replacement therapy as rescue therapy and d) emicizumab plasma levels after loading dose had been completed and patients were on maintenance if measured. Statistical analyses including t-test, chi-square test, and simple logistic regression were utilized to identify associations. All statistical analyses were performed in R.
Results The mean age of the cohort was 29.67 ± 14.45 and 72% self-identified as white non-Hispanic. 58% of our patient sample had breakthrough treated bleeds while on emicizumab. Medication adherence, history of inhibitors and BMI category were not significantly associated with bleeding while on emicizumab. Emicizumab plasma levels were measured in 21 of the patients in our study and ranged from < 5 to 68.9 µg/mL. In individuals who were adherent to their treatment regimen, mean emicizumab levels appeared slightly higher at 35.66 ± 19 compared with 25.66 ± 22.5 in the non-adherent group, however this difference was not statistically significant (p= 0.297). Among the patients who had breakthrough bleeding while on emicizumab, the mean annualized bleeding rates trended lower in those who had measured emicizumab concentrations > 30µg/mL (0.91 ± 0.64) vs 3.07 ± 4.65 in those with emicizumab levels < 30µg/mL, however this difference was not statistically significant (p =0.08). Having breakthrough bleeding while on emicizumab was also not significantly associated with emicizumab plasma levels. Mean emicizumab levels among patients who bled and those who did not were similar (bleeds - 32.06 ± 22.47, no bleeds- 32.87 ± 16.51, p = 0.93). There was no significant association between age, BMI, dosing schedule, or history of inhibitors and emicizumab activity levels in our study sample.
Conclusion Emicizumab plasma levels do not appear to correlate with bleeding events among patients with hemophilia A on emicizumab. However, our study is limited by its small sample size and observational nature. Further clinical studies into the clinical utility of measuring emicizumab plasma levels as well as expanding the inquiry on factors impacting breakthrough bleeding while on emicizumab are necessary.
