Bleeding and safety outcomes in persons with haemophilia A without inhibitors: Results from a prospective non‐interventional study in a real‐world setting

Kruse‐Jarres, Rebecca; Oldenburg, Johannes; Santagostino, Elena; Shima, Midori; Kempton, Christine L.; Kessler, Craig M.; Lehle, Michaela; Chebon, Sammy; Bienz, Nives Selak; Asikanius, Elina; Mahlangu, Johnny

doi:10.1111/hae.13655

Cited by 34 publications

(66 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While real-world data are available for many high-income countries, no such analysis has yet been performed in Austria [ 5 , 6 , 10 ]. The majority of persons with SHA (55.3%) and SHB (83.3%) were on prophylaxis.…”

Section: Discussionmentioning

confidence: 99%

Treatment patterns and bleeding outcomes in persons with severe hemophilia A and B in a real-world setting

Perschy

Rejtő

et al. 2020

Ann Hematol

View full text Add to dashboard Cite

The current standard of care treatment for severe hemophilia A and B (SHA and SHB) is the prophylactic intravenous replacement of coagulation factor VIII or IX (FVIII/FIX) to prevent spontaneous bleeding. Persons with hemophilia without prophylactic treatment receive therapy in case of bleeding, i.e., on demand. To assess treatment patterns, utilization of products, and bleeding outcomes in a real-world cohort of persons with SHA and SHB, defined as FVIII or FIX activity < 1%, data was retrospectively collected from hemophilia-specific patient diaries used for home treatment, medical records, and entries into the Austrian Hemophilia Registry from the year 2012 to 2017. Fifty-three male persons with SHA (n = 47) and SHB (n = 6) were included; 26 with SHA and 5 with SHB were on prophylaxis, 8 and 1 switched therapy regimen, and 13 and 0 received on-demand therapy. Persons on prophylaxis used a mean factor FVIII or FIX dose of 71.7 and 40.1 IU/kg/week. Median (IQR) annualized bleeding rates (ABR) in SHA were 28.0 (23.4–31.3) in the on-demand, 4.9 (1.6–13.5) in the prophylaxis group, and 3.0 (2.0–6.8) in the prophylactic group of SHB. Three persons with SHA had zero bleeds during the observation period. On-demand therapy and hepatitis B and C were associated with higher ABR but not age, weight, and HIV positivity. Bleeding rates and the proportion of on-demand therapy in persons with hemophilia were high in our real-world cohort. Further improvement is needed, which might be facilitated with the advent of factor products with extended half-life or non-factor therapies.

show abstract

Section: Discussionmentioning

confidence: 99%

Treatment patterns and bleeding outcomes in persons with severe hemophilia A and B in a real-world setting

Perschy

Rejtő

et al. 2020

Ann Hematol

View full text Add to dashboard Cite

show abstract

“…The designs, baseline characteristics, and clinical findings of those studies are summarized in Table 1. The data set included data from a total of 445 PwHA; 60 of them only participated in the non-intervention studies [30][31][32], thus data from 385 emicizumab-treated PwHA were included. Study arms where emicizumab was not given were included in the analysis to provide more information on the distribution of bleeds in the absence of emicizumab.…”

Section: Clinical Studies Subjects and Datamentioning

confidence: 99%

Exposure–Bleeding Count Modeling of Emicizumab for the Prophylaxis of Bleeding in Persons with Hemophilia A with/Without Inhibitors Against Factor VIII

et al. 2021

View full text Add to dashboard Cite

Background and Objective Emicizumab is a monoclonal antibody that bridges activated coagulation factor IX and factor X to restore effective hemostasis in persons with hemophilia A. It is indicated for routine prophylaxis of bleeding episodes in persons with hemophilia A. The aim of the present study is to describe the exposure-response relationship between emicizumab concentrations and bleeding frequency, and to confirm adequate bleeding control of the investigated dosing regimens 1.5 mg/kg once weekly, 3 mg/kg every 2 weeks, and 6 mg/kg every 4 weeks. Methods Treated bleeding events were pooled from 445 persons with hemophilia A with and without inhibitors against factor VIII, participating in six clinical studies. Emicizumab concentrations were predicted using a previously developed population pharmacokinetic model. A count model was used to quantify the exposure-response relationship. These models were used to illustrate the relationship between emicizumab concentrations and cumulative count of bleeding over 1 year (annualized bleeding rate). Results The final exposure-response model, based on a generalized Poisson distribution and an inhibitory E max relationship, adequately describes the relationship between daily emicizumab concentrations and daily bleed frequency. A significant effect of factor VIII prophylaxis among persons with hemophilia A without inhibitors was found. Annualized bleeding rate simulations show that the three emicizumab dosing regimens maintain the concentrations close to the plateau of the effect. At the average steady-state concentration across all regimens (53.5 µg/mL), the predicted mean annualized bleeding rate is 1.28, corresponding to a 94.0% reduction from baseline. Conclusions These results confirm that average emicizumab concentrations achieved with all three emicizumab dosing regimens provide adequate bleeding control.

show abstract

“…Prophylactic replacement of FVIII reduces the rate of bleeds and the associated long-term morbidity, and is recognized as optimal care for patients with hemophilia A without inhibitors [8][9][10] . However, even with FVIII prophylaxis, patients experience a residual bleed rate and appreciable long-term joint morbidity 11 . As such, there remains a need for more efficacious therapies.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of emicizumab prophylaxis versus factor VIII prophylaxis for treatment of hemophilia A without inhibitors: network meta-analysis and sub-group analyses of the intra-patient comparison of the HAVEN 3 trial

Reyes

Révil

Niggli

et al. 2019

Current Medical Research and Opinion

Self Cite

View full text Add to dashboard Cite

2019) Efficacy of emicizumab prophylaxis versus factor VIII prophylaxis for treatment of hemophilia A without inhibitors: network meta-analysis and sub-group analyses of the intra-patient comparison of the HAVEN 3 trial, ABSTRACT Objectives: To compare the efficacy of emicizumab prophylaxis with that of factor VIII (FVIII) prophylaxis in patients with hemophilia A without inhibitors using two approaches: network meta-analyses (NMA) and additional sub-group analyses from the HAVEN 3 trial. Methods: The NMA used data from trials identified using a systematic literature review and compared bleed rates in patients receiving emicizumab prophylaxis and patients receiving FVIII prophylaxis using a Bayesian, random effects generalized linear model with log link Poisson likelihood. Additional subgroups of the HAVEN 3 trial included here were defined as patients whose dose-taking behavior met either European label or World Federation of Hemophilia guidelines. A negative binomial regression model was used to conduct an intra-patient comparison of bleed rates within the sub-groups, during treatment with FVIII prophylaxis before entering HAVEN 3 and treatment with emicizumab prophylaxis during HAVEN 3. Results: Four studies were included in the base-case NMA. Evidence showed that the total treated bleed rate was lower with emicizumab prophylaxis compared with FVIII prophylaxis (rate ratio [RR] ¼ 0.36 [95% credible interval (CrI) ¼ 0.13-0.95]). Similar associations were observed in sensitivity analyses. The additional HAVEN 3 analyses also showed lower rates of treated bleeds with emicizumab prophylaxis than with FVIII prophylaxis (RRs [95% confidence interval (CI)] ¼ 0.380 [0.186-0.790] and 0.472 [0.258-0.866] in two sub-groups). These results confirm the original HAVEN 3 intra-patient comparison findings. Conclusions: Combined findings from NMA and additional sub-group analyses of HAVEN 3 support the superiority of emicizumab prophylaxis over FVIII prophylaxis in patients with hemophilia A without inhibitors. ARTICLE HISTORY

show abstract

Bleeding and safety outcomes in persons with haemophilia A without inhibitors: Results from a prospective non‐interventional study in a real‐world setting

Cited by 34 publications

References 24 publications

Treatment patterns and bleeding outcomes in persons with severe hemophilia A and B in a real-world setting

Treatment patterns and bleeding outcomes in persons with severe hemophilia A and B in a real-world setting

Exposure–Bleeding Count Modeling of Emicizumab for the Prophylaxis of Bleeding in Persons with Hemophilia A with/Without Inhibitors Against Factor VIII

Efficacy of emicizumab prophylaxis versus factor VIII prophylaxis for treatment of hemophilia A without inhibitors: network meta-analysis and sub-group analyses of the intra-patient comparison of the HAVEN 3 trial

Contact Info

Product

Resources

About