Emicizumab Dosing in Children and Adults with Hemophilia A: Simulating a User-Friendly and Cost-Efficient Regimen

Bukkems, Laura H.; Fischer, Kathelijn; Kremer-Hovinga, Idske; Donners, Anouk A. M. T.; Fijnvandraat, Karin; Schutgens, Roger E.G.; Cnossen, Marjon H.; Mathôt, Ron A. A.

doi:10.1055/a-1499-0030

Cited by 8 publications

(5 citation statements)

References 13 publications

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“…the other suggests an alternative dosing regimen based on vial size and injection interval. 49 As yet, of the NRTs that may be effective in haemophilia B, none is licensed.…”

Section: Non-replacement Therapy (Nrt)mentioning

confidence: 99%

“…Both studies used Monte Carlo simulations and concluded that rounding the dose is possible and results in cost savings 48,49 . One study refers to an online resource that can help identify the optimum dose 48 ; the other suggests an alternative dosing regimen based on vial size and injection interval 49 …”

Section: Recommendations and Suggested Approachesmentioning

confidence: 99%

“…Two recent studies examined rounding the emicizumab dose to whole vials. Both studies used Monte Carlo simulations and concluded that rounding the dose is possible and results in cost savings 48,49 . One study refers to an online resource that can help identify the optimum dose 48 ; the other suggests an alternative dosing regimen based on vial size and injection interval 49 …”

Section: Recommendations and Suggested Approachesmentioning

confidence: 99%

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Prophylaxis in children with haemophilia in an evolving treatment landscape

et al. 2021

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Introduction For children with haemophilia, early initiation of prophylaxis is crucial to prevent life‐threatening bleeds and maintain joint health throughout life. Options for prophylaxis have recently increased from replacement therapy with standard or extended half‐life coagulation factor products to include other haemostasis products, such as the non‐replacement therapy emicizumab. Aim To review key factors that determine the choice of prophylaxis in young children. Methods Key clinical questions on the implementation of prophylaxis for haemophilia in children were identified and PubMed was searched for evidence supporting guidance on the implementation of prophylaxis. Results The results of the literature search and the practical experience of the authors were used to build consensus on when to start prophylaxis, the pros and cons of the products available to guide the choice of product, and practical aspects of starting prophylaxis to guide the choice of regimen. Conclusions In this era of increasing therapeutic choices, available information about the range of treatment options must be considered when initiating prophylaxis in young children. Parents or care givers must be sufficiently informed to allow informed shared decision making. Although plentiful data and clinical experience have been gathered on prophylaxis with clotting factor replacement therapy, its use in young children brings practical challenges, such as the need for intravenous administration. In contrast, our relatively brief experience and limited data with subcutaneously administered non‐replacement therapy (i.e., emicizumab) in this patient group imply that starting emicizumab prophylaxis in young children requires careful consideration, despite the more convenient route of administration.

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“…the other suggests an alternative dosing regimen based on vial size and injection interval. 49 As yet, of the NRTs that may be effective in haemophilia B, none is licensed.…”

Section: Non-replacement Therapy (Nrt)mentioning

confidence: 99%

Section: Recommendations and Suggested Approachesmentioning

confidence: 99%

Section: Recommendations and Suggested Approachesmentioning

confidence: 99%

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Prophylaxis in children with haemophilia in an evolving treatment landscape

et al. 2021

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“…The research pharmacists of the SYMPHONY consortium will provide a PK-guided dose advice based on a maximum a posteriori (MAP) Bayesian analysis of the individual observed concentration using an online platform https://opticlot.nl 21 22. MAP Bayesian will be performed using NONMEM software (V.7.4.1, Icon Development Solutions, Gaithersburg, Maryland, USA).…”

Section: Methods and Analysismentioning

confidence: 99%

DosEmi study protocol: a phase IV, multicentre, open-label, crossover study to evaluate non-inferiority of pharmacokinetic-guided reduced dosing compared with conventional dosing of emicizumab in people with haemophilia A

et al. 2023

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IntroductionEmicizumab effectively prevents bleeding in people with haemophilia A (PwHA), but is a burden for national healthcare budgets and consequently may limit access. According to the drug label, dosing of emicizumab is based on body weight with fixed intervals of 7, 14 or 28 days, which leads to mean plasma concentrations of 55 µg/mL (SD 15 µg/mL). However, a moderate variability of concentrations and a minimal effective concentration of 30 µg/mL have been suggested in studies. Therefore, a dose of emicizumab that targets a trough concentration of 30 µg/mL is hypothesised to be equally effective as conventional dosing in the prevention of bleeding.Methods and analysisWe designed a phase IV, multicentre, open-label, crossover study to evaluate non-inferiority of bleed control of ≥6 months on conventional dosing in comparison to ≥6 months on dose intervention. This dose intervention consists of reducing the dose of emicizumab to target a trough concentrations of 30 µg/mL using individual pharmacokinetic (PK) parameters. Ninety-five PwHA aged >1 years who received conventional dosing of emicizumab for ≥12 months with good bleeding control during the last 6 months will be recruited from all Dutch haemophilia treatment centres. The study is powered to detect a clinically relevant decrease (risk difference) of 15% in the proportion of patients without treated bleeds during follow-up. Secondary endpoints are spontaneous joint or muscle bleeds, and annualised treated bleeding rates (using negative binomial regression). Cost-effectivity between conventional dosing and individualised PK-guided dosing of emicizumab will be compared.Ethics and disseminationThe DosEmi study was approved by the Medical Ethics Review Committee NedMec of the University Medical Center of Utrecht, The Netherlands. Study results will be communicated through publications in international scientific journals and presentations at (inter)national conferences.Trial registration numberEUCTR2021-004039-10-NL athttps://trialsearch.who.int.Protocol versionV.4.1 on 28 October 2022 (DosEmi protocol_V4.1; NL81112.041.22).

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“…Also, in the Netherlands, Bukkems et al 91 reported an alternative simulated dosing regimen, with a target median emicizumab plasma concentration between 40 and 60 µg/mL at steady state. The authors reported that costs were saved in up to 60% of the virtual population and could reach a median of almost 60 000 euros.…”

Section: Isth 2021 Virtual Congressmentioning

confidence: 99%