Donners Anouk A M T, van der Zwet Konrad, Rademaker Carin M A, Egberts Toine C G, Schutgens Roger E G, Fischer Kathelijn
Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Van Creveldkliniek, Center for Benign Haematology, Thrombosis and Haemostasis, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
Res Pract Thromb Haemost. 2023 Feb 8;7(2):100074. doi: 10.1016/j.rpth.2023.100074. eCollection 2023 Feb.
Prophylaxis with emicizumab provides effective bleeding protection in persons with hemophilia A (PwHA) but pressures healthcare budgets. The body weight-adjusted dosing at 7-, 14-, or 28-day intervals, according to the label, often mismatches the vial content. Entire-vial dosing resulted in therapeutic concentrations according to pharmacokinetic simulations and was introduced to avoid waste.
The objective of this study was to evaluate the efficacy of entire-vial dosing of emicizumab by investigating real-world evidence of plasma concentrations, bleeds, and drug waste.
This is a single-center, observational study with PwHA receiving emicizumab in mg/kg doses according to label but dosing interval extrapolated to the nearest vial size. Patient characteristics and bleeds were compared 1 year before starting emicizumab and during emicizumab until January 2022. Concentrations were assessed at weeks 4, 12, and annually. The mean (95% CI) annualized bleed rates were compared by using negative binomial regression. Drug waste between label-based dosing and entire-vial dosing was compared.
A total of 112 individuals (94% severe phenotype and 9% positive FVIII inhibitors) were followed for a median of 56 weeks (interquartile range [IQR] 52-68) before and 51 weeks (IQR 29-75) after starting emicizumab. The median emicizumab dose was 5.9 (IQR 5.5-6.2) mg/kg/4 wk with median concentrations of 63 (IQR 51-80) μg/mL. The annualized bleed rate of treated bleeds before emicizumab was 3.6 (95% CI 2.9-4.4) and was 0.8 (95% CI 0.6-1.1) during emicizumab ( < .001). Drug waste was reduced by 9%.
The entire-vial dosing of emicizumab is an attractive treatment option for PwHA leading to therapeutic plasma concentrations, good bleeding control, and drug waste avoidance.
使用艾美赛珠单抗进行预防可为甲型血友病患者（PwHA）提供有效的出血保护，但会给医疗预算带来压力。根据标签，按体重调整剂量，每7、14或28天给药一次，通常与药瓶内容量不匹配。根据药代动力学模拟，整瓶给药可达到治疗浓度，因此采用整瓶给药以避免浪费。
本研究的目的是通过调查血浆浓度、出血情况和药物浪费的真实世界证据，评估艾美赛珠单抗整瓶给药的疗效。
这是一项单中心观察性研究，PwHA按照标签以mg/kg剂量接受艾美赛珠单抗治疗，但给药间隔根据最接近的药瓶大小进行外推。比较开始使用艾美赛珠单抗前1年以及使用艾美赛珠单抗至2022年1月期间的患者特征和出血情况。在第4周、第12周和每年评估浓度。使用负二项回归比较平均（95%CI）年化出血率。比较基于标签给药和整瓶给药之间的药物浪费情况。
共纳入112例患者（94%为重型表型，9%为FVIII抑制剂阳性），在开始使用艾美赛珠单抗前中位随访56周（四分位间距[IQR]52 - 68），开始使用后中位随访51周（IQR 29 - 75）。艾美赛珠单抗的中位剂量为5.9（IQR 5.5 - 6.2）mg/kg/4周，中位浓度为63（IQR 51 - 80）μg/mL。使用艾美赛珠单抗前治疗性出血的年化出血率为3.6（95%CI 2.9 - 4.4），使用期间为0.8（95%CI 0.6 - 1.1）（P <.001）。药物浪费减少了9%。
艾美赛珠单抗整瓶给药对于PwHA是一种有吸引力的治疗选择，可导致治疗性血浆浓度、良好的出血控制并避免药物浪费。
