Performance of a Drug-Specific Calibration Curve for Monitoring Treatment With Albutrepenonacog Alfa: A Multicenter Study in Argentina.

Abstract

Introduction: Laboratory testing is important for ensuring treatment effectiveness of hemophilia B. The most widely used laboratory test to measure factor IX (FIX) activity is the modified activated partial thromboplastin time (aPTT, one-stage clotting assay [OSA]). Concerns emerged about albutrepenonacog alfa (Idelvion) impact on laboratory measurement. We aimed to evaluate a product-specific calibration curve for determining the activity of Idelvion in Argentina.

Methods: In our nationwide, prospective, noninterventional study, a product-specific calibration standard (PCS) was prepared from a reconstituted vial. Commercial FIX-deficient plasma (FIXdp) spiked with Idelvion was used as a normal control (NC:0.7 IU/mL) and low control (LC:0.1 IU/mL). A drug-specific OSA calibration curve was constructed starting from 1.0 IU/mL, followed by serial dilutions. Thirteen different aPTT reagents were used.

Results: Thiry-six results from 27 Care Centers were retrieved. Median (interquartile range [IQR]) NC local standard human plasma (LSH) and NC PCSs were 0.48 IU/mL (0.38-0.92) and 0.72 IU/mL (0.58-0.82), respectively. Coefficients of variation (CVs) for NC LSH and PCS were 44.6% and 24.8%, respectively; recovery rates (± 20%) were 22% and 83%. Median LC LSH and PCS were 0.09 IU/mL (0.07-0.13) and 0.10 IU/mL (0.07-0.13), respectively; CVs for LC LSH and PCS were 104.8% and 24.7%. Recovery rates (±30%) were 58% and 89%.

Conclusion: Idelvion-specific calibration curve showed better performance and lower CV rates independently of the aPTT reagent or the platform used. Calibration using this specific standard might allow more laboratories to obtain acceptable FIX values when processing NC and LC levels and patients' plasmas.