scholarly journals Turoctocog alfa pegol provides effective management for major and minor surgical procedures in patients across all age groups with severe haemophilia A: Full data set from the pathfinder 3 and 5 phase III trials

Haemophilia ◽  
2020 ◽  
Vol 26 (3) ◽  
pp. 450-458
Author(s):  
Alberto Tosetto ◽  
Anne Neff ◽  
Steven R. Lentz ◽  
Elena Santagostino ◽  
Laszlo Nemes ◽  
...  
Keyword(s):  
Surgical Procedures ◽  
Age Groups ◽  
Phase Iii ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Effective Management ◽  
Full Data ◽  
Data Set ◽  
Minor Surgical Procedures ◽  
Phase Iii Trials

Management of Haemophilia in Sweden

1976 ◽  
Vol 35 (03) ◽  
pp. 510-521 ◽  
Author(s):  
Inga Marie Nilsson
Keyword(s):  
Factor Viii ◽  
Total Population ◽  
Age Groups ◽  
Factor Ix ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Haemophilia B ◽  
Human Fraction ◽  
Mild Haemophilia

SummaryThe incidence of living haemophiliacs in Sweden (total population 8.1 millions) is about 1:15,000 males and about 1:30,000 of the entire population. The number of haemophiliacs born in Sweden in 5-year periods between 1931-1975 (June) has remained almost unchanged. The total number of haemophilia families in Sweden is 284 (77% haemophilia A, 23% haemophilia B) with altogether 557 (436 with A and 121 with B) living haemophiliacs. Of the haemophilia A patients 40 % have severe, 18 % moderate, and 42 % mild, haemophilia. The distribution of the haemophilia B patients is about the same. Inhibitors have been demonstrated in 8% of the patients with severe haemophilia A and in 10% of those with severe haemophilia B.There are 2 main Haemophilia Centres (Stockholm, Malmo) to which haemophiliacs from the whole of Sweden are admitted for diagnosis, follow-up and treatment for severe bleedings, joint defects and surgery. Minor bleedings are treated at local hospitals in cooperation with the Haemophilia Centres. The concentrates available for treatment in haemophilia A are human fraction 1-0 (AHF-Kabi), cryoprecipitate, Antihaemophilic Factor (Hyland 4) and Kryobulin (Immuno, Wien). AHF-Kabi is the most commonly used preparation. The concentrates available for treatment in haemophilia B are Preconativ (Kabi) and Prothromplex (Immuno). Sufficient amounts of concentrates are available. In Sweden 3.2 million units of factor VIII and 1.0 million units of factor IX are given per year. Treatment is free of charge.Only 5 patients receive domiciliary treatment, but since 1958 we in Sweden have practised prophylactic treatment of boys (4–18 years old) with severe haemophilia A. At about 5-10 days interval they receive AHF in amounts sufficient to raise the AHF level to 40–50%. This regimen has reduced severe haemophilia to moderate. The joint score is identical with that found in moderate haemophilia in the same age groups. For treatment of patients with haemophilia A and haemophilia B complicated by inhibitors we have used a large dose of antigen (factor VIII or factor IX) combined with cyclophosphamide. In most cases this treatment produced satisfactory haemostasis for 5 to 30 days and prevented the secondary antibody rise.

Safety and efficacy of sucrose-formulated full-length recombinant factor VIII: Experience in the standard clinical setting

2008 ◽  
Vol 99 (01) ◽  
pp. 52-58 ◽  
Author(s):  
Elena Santagostino ◽  
Albert Faradji ◽  
Alfonso Iorio ◽  
Jan van der Meer ◽  
Jørgen Ingerslev ◽  
...  
Keyword(s):  
Observational Study ◽  
Factor Viii ◽  
De Novo ◽  
Observation Time ◽  
Full Length ◽  
Recombinant Factor Viii ◽  
Phase Iii ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Safety And Efficacy

SummaryThe safety of full-length sucrose-formulated recombinant factor VIII (rFVIII-FS; KOGENATE® FS) for up to 24 months of use was evaluated in a postmarketing observational study in Europe. Long-term safety and efficacy data were available for 212 patients with severe haemophilia A, including 13 previously untreated patients (PUPs) and 12 patients with 1–19 exposure days (EDs). Patients accumulated a mean (± SD) of 187 (121) EDs to rFVIII-FS and received a total of 39,627 infusions, mainly for prophylaxis and for the treatment of 4,283 spontaneous or trauma-related bleeds during an average observation time of 710 (136) days. Of these bleeding episodes, 85.4% were successfully treated with one or two infusions of rFVIII-FS. Haemostasis was also evaluated during 46 minor to major surgical pro- cedures, and the response to infusion was “excellent” or “good” in all cases. FVIII inhibitor formation was observed in six patients (two de novo; four persistent or recurrent). The de novo cases represent 8.0% (2 of 25) of patients who reported 0–19 previous EDs at study entry. Four of the five patients who reported possible drug-related adverse effects developed inhibitors. The results of this observational study demonstrate the efficacy and safety of rFVIII-FS during normal clinical use in the treatment of patients with severe haemophilia A. Furthermore, these findings are consistent with those of previous phase III clinical studies with rFVIII-FS, particularly with regard to its efficacy and low incidence of inhibitor formation.

Comparison of the Efficacy and Toxicity of Fludarabine (F) in First Line Therapy of Younger Versus Elderly Patients (Pts) with Advanced Chronic Lymphocytic Leukemia (CLL): Results of a Meta-Analysis of Two Phase III Trials of the German CLL Study Group (GCLLSG).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 717-717 ◽  
Author(s):  
Barbara F. Eichhorst ◽  
Raymonde Busch ◽  
Clemens M. Wendtner ◽  
Michael Hallek ◽  
Keyword(s):  
Age Groups ◽  
The Elderly ◽  
Phase Iii ◽  
First Line ◽  
Two Phase ◽  
First Line Therapy ◽  
Line Therapy ◽  
Phase Iii Trials ◽  
Binet Stage ◽  
Grade 3

Abstract Introduction: F based regimen have become the standard treatment in CLL at least in younger pts. However, in elderly pts chlorambucil is still frequently used since it is easy to administer and has less side effects. Here we compare the efficacy and toxicity of F administered to younger pts and elderly pts treated between 1999 and 2004 within two phase III trials of GCLLSG. Patients: 362 pts (median age 59 [range 37–65] years) were randomized to F (n=182) or F plus cyclophosphamide (n=180) within the CLL4 trial. 191 elderly pts (median age 71 [range 65–79] years) were treated with F (92 pts) or chlorambucil (99 pts) within the CLL5 protocol. Inclusion criteria were identical in both trials except for age limits. All pts were previously untreated and in advanced stage Binet C or Binet B with symptoms which require therapy or Binet A with severe B-symptoms. In both studies the F regimen consisted of 30 mg/m2/day (d) IV for 5 consecutive days, every 28 d for up to 6 cycles. Anti-infective prophylaxis and growth factors were not given routinely in both trials. Results: Most of patients in both age groups were in Binet stage B (54% of the younger pts and 52% of the elderly), 35% in each age group were in Binet stage C, 11% and 13% respectively in Binet stage A. No significant difference in the main clinical features was observed except for a higher incidence of concomitant disease in the elderly (61% versus 36%, p=0.001). A mean number of 5.2 F courses was administered in the CLL4 trial and 4.9 courses in the CLL5 trial. The mean administered cumulative dose of F per pt was lower in the elderly pts (1076 mg vs. 1194 mg, p= 0.05). Overall response rates were similar in both arms, with 82.9% in the younger group and 85.7% in the elderly. The complete remission rate was 6.7% in the younger patients and 10.4% in the elderly (p= 0.3). After a follow up time of 24 months (mo) the progression-free survival (PFS) was significantly shorter in the elderly group with 18.7 mo compared to 19.8 mo in the younger group after 22 mo observation time (p=0.03). The overall survival (OS) was significantly impaired in elderly pts as well (29 mo versus median not reached, p<0.001). Progressive disease was the main cause of death in both age groups. In each group 3 treatment related deaths occurred due to infection or hemolysis. The incidence of side effects was similar in both age groups. Severe, CTC grade 3 and 4, myelosuppression occurred in 39% of the younger and 41% of the elderly pts. No difference in the rate of leukocytopenia, thrombocytopenia or anemia was oberved as well. The incidence rate and severity of infections was similar in both groups (24% vs. 32% all and 8.7% vs. 6.9% CTC grade 3 and 4). The incidence of second neoplasia was significantly higher in the elderly pts (2.2% vs. 12.2%, p=0.001). In comparison the prevalence rate of neoplasia in the U.S. population peaks at 11% in the age group of 70–79 (SEER cancer statistic review: 1972–2002). Conclusion: F is a well tolerated treatment regimen in first line therapy of elderly pts with CLL. Response rates were similar in both age groups. PFS and OS were significantly shorter in the elderly population. The incidence of second neoplasia was significantly higher in the elderly pts, but is only slightly increased in comparison to the normal population.

Xyntha®is effective and safe in previously treated patients with severe haemophilia A: Final results of a pivotal phase III study

Haemophilia ◽  
2009 ◽  
Vol 15 (2) ◽  
pp. 635-635
Author(s):  
KATIA EVANS ◽  
ROBERT JANCO ◽  
CHANDRASEKHAR UDATA ◽  
AMANDA O’BRIEN ◽  
BROOKE HAYWARD ◽  
...  
Keyword(s):  
Phase Iii ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Pivotal Phase ◽  
Phase Iii Study ◽  
Previously Treated Patients ◽  
Previously Treated

scholarly journals Not All Patients Benefit from Switching to Ehl: Results from the Wapps Database

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 21-22
Author(s):  
Olav Versloot ◽  
Emma Iserman ◽  
Pierre Chelle ◽  
Federico Germini ◽  
Tushara Mathew ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Half Life ◽  
Research Funding ◽  
Large Scale ◽  
Age Groups ◽  
Relative Increase ◽  
Pharmacokinetic Data ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Haemophilia B

Introduction: Extended Half-Life (EHL) concentrates were recently introduced to increase trough levels, decrease infusion frequency and potentially limiting the burden of treatment in patients with haemophilia (PWH) and their caregivers. Group-based studies have reported increased terminal half-life (THL) after switching from standard half-life (SHL) to EHL concentrates. However, available reports have included less than 30 patients and large-scale studies on switching from SHL to EHL concentrates are lacking. Aim: to assess individual changes in THL after switching from SHL to EHL concentrates in patients with severe haemophilia. Methods: Data were collected from the WAPPS (Web-Accessible Population Pharmacokinetics Service; www.wapps-hemo.org) database, which aims to assemble a database of pharmacokinetic data in PWH, develop and validate population pharmacokinetics models, and integrate these models within a Web-based calculator for individualized pharmacokinetic estimation. Informed consent was waived by the ethical committee. Data were selected from patients with both SHL and EHL infusions available. In case of multiple data, the last SHL and first EHL infusion were selected. THL was compared according to haemophilia type and age groups (children/adults). Comparisons were made based on haemophilia type and age by means of non-parametric paired testing. Results: Data were collected from 649 patients (1298 infusions) with severe haemophilia (89% haemophilia A; median age: 21.7 (11.5-37.7), weight: 66.0 kg (43.6-80.0) BMI: 22.5 (18.9-25.3); positive inhibitor history: 11.7%). All patients had received both SHL and EHL infusions. THL increased by a median factor 1.4 (1.2-1.7) in FVIII, leading to an absolute median increase of 4.1 hours (IQR: 2.0-6.7). However, THL was extended by less than 20% in 157 (27,2%) patients with haemophilia A after switching to EHL concentrates, leading to less than 48 minutes extension of THL. THL showed a decrease in 57 (9,9%) patients with haemophilia A after switching. For patients switching to EHL FIX, THL increased by a median factor 3.1 (2.4-3.6), leading to a median extension of 70.3 (52.5-90.8) hours in THL of FIX. All patients with haemophilia B showed an extension of THL after switching, with a minimum increase of 25%. Both the absolute and the relative increase in THL were similar for children and adults for both FVIII and FIX. Discussion: This was the first study to report large scale data on PWH switching from SHL to EHL concentrates. The results show that although an increased THL was observed at a group level, this was not the case for all individual patients. THL was extended by less than 20% after switching in 27% of patients with haemophilia A, with an actual decrease in THL in 9.9%. THL was extended by a minimum of 25% in patients with haemophilia B. This seems to support the use of individualized PK assessment in patients with haemophilia to guide clinical decisions on switching from SHL to EHL concentrates. Disclosures Versloot: Bayer: Research Funding. Germini:Bayer: Research Funding; NovoNordisk: Research Funding; Roche: Research Funding; Takeda: Research Funding. Iorio:Freeline: Research Funding; Pfizer: Research Funding; NovoNordisk: Research Funding; CSL: Research Funding; BioMarin: Research Funding; Octapharma: Research Funding; Takeda: Research Funding; Uniqure: Research Funding; Grifols: Research Funding; Roche: Research Funding; Bayer: Research Funding; Sanofi: Research Funding; Spark: Research Funding. Fischer:Bayer, Biogen, Pfizer, Baxter/Shire, and Novo Nordisk: Research Funding; Bayer, Baxter/Shire, SOBI/Biogen, CSL Behring, Octapharma, Pfizer, NovoNordisk: Research Funding; Bayer, Baxter, Biogen, CSL Behring, Freeline, Novo Nordisk, Pfizer, Roche, and Sobi: Consultancy.

Efficacy, Immunogenicity, Pharmacokinetics, and Safety Of Human-cl rhFVIII – a GCP Study In Children With Severe Haemophilia A

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3594-3594
Author(s):  
Raina Liesner ◽  
Martina Jansen ◽  
Anna Klukowska ◽  
Vladimir Vdovin ◽  
Tomasz Szczepanski ◽  
...  
Keyword(s):  
Age Groups ◽  
Human Cell Line ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Central Laboratory ◽  
One Stage ◽  
Previously Treated ◽  
Bleeding Episodes ◽  
The One

Abstract Introduction Human-cl rhFVIIIis the first recombinant factor VIII concentrate expressed in a human cell line (Human Embryonic Kidney 293F cells). Studies in adolescent and adult pre-treated patients with severe haemophilia A showed a favorable PK profile with a median half-life of 17.1 hours (one stage assay) and indicated safety and efficacy in preventing and treating bleeding episodes (BE). Aims The objectives of this international GCP study were to evaluate the efficacy, safety, immunogenicity and pharmacokinetic (PK) properties of Human-cl rhFVIIIin previously treated children between 2 and 12 years of age. Methods All patients started with an in-vivo recovery (IVR) investigation and in a subset of patients, the PK of Human-cl rhFVIII was assessed in comparison to the patient’s previously used FVIII product. After an injection of 50 IU/kg, blood samples were collected up to 48 hours for PK analysis and up to 2 hours for IVR. IVR was repeated in all patients after 3 and 6 months. FVIII plasma levels were measured by chromogenic and one-stage assay in a central laboratory. Patients were treated prophylactically with Human-cl rhFVIII every other day or 3x weekly, injecting 30-40 IU Human-cl rhFVIIIper kg for at least 6 months and > 50 exposure days. Inhibitors were measured before, during and at the end of the study by modified Nijmegen Bethesda assay in a central laboratory. Adverse events were recorded throughout the study. Results 59 patients (29: 2-5 years; 30: 6-12 years) were enrolled from 15 specialized sites in Europe. 13 children of each age group participated in the comparative PK investigation. Mean PK parameters of Human-cl rhFVIII were similar in both age groups for both the chromogenic and the one-stage assay: AUCnorm 0.23 vs. 0.24 h*IU/mL/[IU/kg]); IVR 1.88 vs. 1.61% per IU/kg; T1/2 9.7 vs. 12.5 h. IVR remained stable throughout the study. A total of 108 BEs in 32/59 patients were treated with Human-cl rhFVIII. The majority of treated BEs were traumatic (60.2%) and minor (56.5%). The mean ± SD monthly bleeding rate of all types of BEs/patient was 0.34±0.43 (spontaneous BEs: 0.12±0.27; traumatic BEs: 0.19±0.29). No inhibitor development was reported; no patient discontinued the study because of an AE. Conclusion The data indicate that Human-cl rhFVIII is efficacious and safe in preventing and treating BEs in previously treated children. The PK of Human-cl rhFVIII was comparable in both studied age groups. Disclosures: Liesner: Octapharma AG: Consultancy, Investigator Other. Jansen:Octapharma AG: Employment. Klukowska:Octapharma AG: Investigator Other. Vdovin:Octapharma AG: Investigator Other. Szczepanski:Octapharma AG: Investigator Other. Knaub:Octapharma AG: Employment.

Efficacy of a sucrose-formulated recombinant factor VIII used for 22 surgical procedures in patients with severe haemophilia A

Haemophilia ◽  
2000 ◽  
Vol 6 (6) ◽  
pp. 614-618 ◽  
Author(s):  
I. Scharrer ◽  
H.-H. Brackmann ◽  
Y. Sultan ◽  
T. Abshire ◽  
C. Gazengel ◽  
...  
Keyword(s):  
Factor Viii ◽  
Surgical Procedures ◽  
Recombinant Factor Viii ◽  
Haemophilia A ◽  
Severe Haemophilia

Efficacy and safety of Nuwiq®(human-cl rhFVIII) in patients with severe haemophilia A undergoing surgical procedures

Haemophilia ◽  
2017 ◽  
Vol 24 (1) ◽  
pp. 70-76 ◽  
Author(s):  
N. Zozulya ◽  
C. M. Kessler ◽  
A. Klukowska ◽  
M. von Depka ◽  
K. Hampton ◽  
...  
Keyword(s):  
Surgical Procedures ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Efficacy And Safety
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