SYMPHONY consortium: Orchestrating personalized treatment for patients with bleeding disorders

Cnossen, Marjon H.; Moort, Iris van; Reitsma, Simone H.; Maat, Moniek P.M. de; Schutgens, Roger E. G.; Urbanus, Rolf T.; Lingsma, Hester F.; Mathôt, Ron A. A.; Gouw, Samantha C.; Meijer, Karina; Bredenoord, Annelien L.; Graaf, Rieke van der; Fijnvandraat, Karin; Meijer, Alexander B.; Akker, Emile van den; Bierings, Ruben; Eikenboom, Jeroen; Biggelaar, Maartje van den; Haas, Masja de; Voorberg, Jan; Leebeek, Frank W.G.

doi:10.1111/jth.15778

Cited by 8 publications

(8 citation statements)

References 47 publications

(112 reference statements)

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“…The study team of the coordinating centre meets weekly. A multidisciplinary study steering committee has been installed, consisting of (but not limited to) haemophilia clinicians, pharmacists, representative from the Dutch Haemophilia Patients Organisation and the SYMPHONY consortium for valued based healthcare support and PK guidance 21. Study monitoring will be performed by a professional contract research organisation (Julius Clinical, Zeist, the Netherlands).…”

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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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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“…Women with a bleeding tendency or underlying bleeding disorder may experience various bleeding symptoms in addition to HMB, with which women may present at the outpatient clinic [6] . An overall bleeding history besides a obstetrical-gynecological history is an important factor in reducing diagnostic delay in bleeding disorders and could be crucial in optimizing HMB management [7], [8], [9], [10,11] .…”

Section: Introductionmentioning

confidence: 99%

Total Self-BAT scores associated with choice of heavy menstrual bleeding treatment

Eising,

Punt,

Grimberg

et al. 2024

Preprint

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Background Heavy menstrual bleeding (HMB) is frequently the indicating symptom of an underlying bleeding disorder. The self-administered bleeding assessment tool (self-BAT) provides an overview of the bleeding history and indication of a bleeding tendency. Research about the association between a bleeding tendency and choice of HMB treatment is scarce. Methods The self-BAT was sent to all adult patients with HMB seeking care at a gynecological clinic. Closed questions on medical and surgical HMB management were provided, as well as a free-text question to reflect on personal experiences and opinions concerning HMB management. For clinical assessment of bleeding tendency, the cut-off for an abnormal self-BAT score was ≥5 in young women (18-30 years) or ≥6 for women of 31-52 years. Results Overall, 36% (234/650) of eligible women completed the questionnaire. The median total self-BAT score was 6 (interquartile range: 0–17). An abnormal total self-BAT score was more prevalent in women who underwent a hysterectomy compared to those who had not for women age 31-52 years (OR 4.3; 95%CI,1.2; 15.3; p=0.02). Medical therapy (hormonal, tranexamic acid or iron) was more prescribed in women with an abnormal self-BAT score. The most frequently mentioned responses from patients were related to low awareness of the effects of HMB and the need for patient empowerment. Conclusions Findings imply that there is a substantial group of patients with HMB who experience a bleeding tendency. This bleeding tendency may influence the choice of HMB treatment like a hysterectomy. Structured bleeding assessment tools could guide optimal diagnostics and treatment for women with HMB.

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“…In turn, the medical management of these patients was transformed by molecularly defining their disorder, which has often, though with a number of notable exceptions, led to disease‐specific replacement therapies with better and safer hemostatic efficacy. These complementing endeavors will be further synchronized within SYMPHONY, a new Dutch research consortium described in detail in this issue by Cnossen et al and outlined on their website 3,4 . This enviable scientific program builds on the strong track records of clinical and basic‐science hemostatic research in the Netherlands.…”

mentioning

confidence: 97%

“…These complementing endeavors will be further synchronized within SYMPHONY, a new Dutch research consortium described in detail in this issue by Cnossen et al and outlined on their website. 3,4 This enviable scientific program builds on the strong track records of clinical and basic-science hemostatic research in the Netherlands. SYMPHONY aims to ultimately enhance the clinical care of people with hemorrhagic disorders by better describing their bleeding diathesis to account for interindividual variation in bleeding behavior and response to therapy.…”

mentioning

confidence: 99%

A new harmony for hemorrhagic disorders: The Dutch SYMPHONY consortium

Samelson-Jones

2022

Journal of Thrombosis and Haemostasis

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SYMPHONY consortium: Orchestrating personalized treatment for patients with bleeding disorders

Cited by 8 publications

References 47 publications

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

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

Total Self-BAT scores associated with choice of heavy menstrual bleeding treatment

A new harmony for hemorrhagic disorders: The Dutch SYMPHONY consortium

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