PB0539 - Analysis of emicizumab plasma concentrations in single centre cohort of people with Haemophilia A on emicizumab prophylaxis

Background: The FVIIIa-mimicking monoclonal antibody emicizumab is increasingly widely used as bleed prophylaxis in haemophilia A. Dosing is fixed weight-based and monitoring of plasma concentration is not routinely required

Aims: To (i) assess emicizumab plasma concentrations in people with haemophilia A (PwHA) treated with standard weight-based dosing and (ii) assess the clinical utility of such measurements.

Methods: Emicizumab plasma concentrations were routinely measured in all PwHA receiving maintenance-phase emicizumab attending for clinical review in a regional haemophilia centre, between October 2018 and October 2023. A modified one-stage APTT-based assay calibrated against emicizumab was used. Levels were retrospectively analysed.

Results: 267 emicizumab plasma concentrations were available in 83 PwHA, corresponding to a median of 3 levels per patient (range 1-11). Included PwHA had median age 37 years (18-77), weight 81kg (52-164) and 27.7% had FVIII inhibitors. Median emicizumab duration was 35 months (2-87). 63.9% were on weekly dosing and 36.1% fortnightly. Median emicizumab concentration was 58 mg/ml (IQR 36-58) for all patients. Levels tended to be lower with weekly vs fortnightly dosing (45 vs 55 mg/ml, p< 0.0001 (Mann Whitney)) (Figure 1). Significant intra-individual variation was observed (Figure 2), not explained by dose- or weight- changes. No thrombotic complications were observed. 14/83 (16.8%) of patients had
≥1 level < 30 mg/ml. No spontaneous joint/muscle bleeds occurred in this subgroup, but 2/14 experienced rectal bleeding. 6/14 weighed over 115kg and 8/14 were not fully compliant with the treatment regime.

Conclusion(s): Emicizumab appears to be clinically effective over a wide range of plasma concentrations. Observed variability in levels may be explained in part by blood draw at varying points in the dosing cycle, but extreme BMI, treatment compliance and presence of anti-emicizumab antibodies could also contribute. Routine monitoring allows identification of individuals with low levels, so that treatment concordance can be reviewed and anti-emicizumab antibody investigation considered.