scholarly journals The PUP-GCP Clinical Trial: A Low Inhibitor Rate in Previously Untreated Patients with Severe Hemophilia a Treated with Octanate

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5051-5051
Author(s):  
Sigurd Knaub ◽  
Anna Klukowska ◽  
Vladimir Komrska ◽  
Pawel Laguna ◽  
Vdovin Vladimir ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Rating Scale ◽  
Hemophilia A ◽  
High Titer ◽  
Large Deletion ◽  
Severe Hemophilia ◽  
On Demand ◽  
Intron 22 Inversion ◽  
Bleeding Episodes ◽  
Inhibitor Patient

Abstract Background : Octanate is a highly purified, double virus inactivated, human plasma-derived factor VIII (FVIII) concentrate with all coagulation FVIII bound to its natural stabilizer VWF in a VWF:RCo/FVIII:C ratio of approximately 0.4. A prospective clinical trial has been initiated in 2000 in order to assess the immunogenicity, efficacy and tolerability of Octanate in previously untreated patients (PUPs). Materials and Methods: Patients with severe hemophilia A without previous exposure to FVIII or FVIII-containing products were enrolled. Inhibitor screening, using the modified Bethesda method, was performed prior to treatment, starting every 3-4 EDs (ED 1-20), and afterwards every 10 EDs (ED 21-100), but at least every three months. Efficacy and tolerability were assessed by a 4-point verbal rating scale. Results: The study is clinically completed, after fifty-one subjects with severe haemophilia A, at screening 0,01-5,61 years old (median 0,65 years; median 0,99 years at treatment start) have been enrolled. Three of them developed clinically relevant high titer inhibitors over the course of the study. Another two displayed transient inhibitors that disappeared spontaneously without changing the dose or dosing interval. All inhibitors developed under on-demand treatment and before ED 50. For 4 inhibitor patients an intron 22 inversion, for 1 inhibitor patient a large deletion of exons 7 – 12 was found. From 51 subjects, 45 exceeded 50 EDs. Octanate was well-tolerated and the adverse event profile was consistent with the population studied. The haemostatic efficacy in prophylaxis and treatment of bleeding episodes was generally rated as “excellent” and no complication was reported for any surgical treatment. Conclusion: Despite frequent inhibitor testing and predominant on-demand treatment, the data indicate a low overall inhibitor rate for Octanate in patients who exceeded 50 EDs (5/45) of which only 3 (6.7%) were clinically relevant. Disclosures Knaub: Octapharma AG: Employment. Klukowska:Octapharma AG: Investigator Other. Komrska:Octapharma AG: Investigator Other. Laguna:Octapharma AG: Investigator Other. Vladimir:Octapharma AG: Investigator Other. Jansen:Octapharma AG: Employment.

Latest Results From The PUP-GCP Clinical Trial: A Low Inhibitor Rate In Previously Untreated Patients With Severe Hemophilia A Treated With Octanate

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3596-3596
Author(s):  
Anna Klukowska ◽  
Martina Jansen ◽  
Vladimir Komrska ◽  
Pawel Laguna ◽  
Vladimir Vdovin ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Rating Scale ◽  
Hemophilia A ◽  
Severe Hemophilia ◽  
Observational Period ◽  
Adverse Event Profile ◽  
On Demand ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Bleeding Episodes

Abstract Background Octanate is a highly purified, double virus inactivated, human plasma-derived factor VIII (FVIII) concentrate with all coagulation FVIII bound to its natural stabilizer VWF in a VWF:RCo/FVIII:C ratio of approximately 0.4. Five prospective GCP studies with octanate were conducted in 77 previously treated patients (PTPs) with severe hemophilia A. None of these 77 PTPs developed an inhibitor while treated exclusively with octanate. Aim To assess the immunogenicity in previously untreated patients (PUPs), a prospective clinical trial has been initiated in 2000. This included 50 PUPs with severe hemophilia A for an observational period of 100 exposure days with octanate, for at least 6 months. Methods Patients with severe hemophilia A without previous exposure to FVIII or FVIII-containing products were enrolled. Efficacy and tolerability were assessed by a 4-point verbal rating scale. Inhibitors were assessed according to modified Bethesda method prior to treatment every 3-4 exposure days (ED 1-20), and after treatment every 10 EDs (ED 21-100), but at minimum every three months. Results Two of 50 (4%) subjects developed clinically relevant inhibitor titers over the course of the study. Another two displayed inhibitors that disappeared spontaneously without change of dose or dosing interval. All inhibitors developed under on-demand treatment and before ED 50. From the 50 subjects, 42 had exceeded 50 EDs at the time of this analysis. Octanate was well-tolerated and the adverse event profile was consistent with the population studied. The hemostatic efficacy in prophylaxis and treatment of bleeding episodes was generally rated as “excellent” and no complication was reported for any surgical treatment. Conclusion Despite frequent inhibitor testing and predominant on-demand treatment, the data indicate a low overall inhibitor rate for octanate in patients who exceeded 50 exposure days (4/42) of which only 2 (4.8%) were clinically relevant. Disclosures: Klukowska: Octapharma AG: Investigator Other. Jansen:Octapharma AG: Employment. Komrska:Octapharma AG: Investigator Other. Laguna:Octapharma AG: Investigator Other. Vdovin:Octapharma AG: Investigator Other. Knaub:Octapharma AG: Employment.

scholarly journals Safety and Efficacy of New Moroctocog Alfa Drug (Octofactor) in Prophylactic Treatment in Adolescent Patients with Severe and Moderate Hemophilia a

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4703-4703 ◽  
Author(s):  
Ekaterina Shiller ◽  
Vladimir Vdovin ◽  
Victor Petrov ◽  
Pavel Svirin ◽  
Tatiana Andreeva ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Prophylactic Treatment ◽  
Hemophilia A ◽  
Residual Activity ◽  
Severe Hemophilia ◽  
Efficacy Evaluation ◽  
Spontaneous Bleeding ◽  
On Demand ◽  
Number Of Patients ◽  
Bleeding Episodes

Abstract Efficacy and safety of a new domestically produced rFVIII-BDD (moroctocog alfa, Octofactor, CJSC "GENERIUM", Russia) was investigated in a controlled, open, prospective, multicenter clinical trial. After screening and a 4-days washout period 12 previously treated patients adolescents (age 12-18 years old) with severe hemophilia A (the activity of FVIII was less than 1%) were included in the clinical trial. The patients were given the moroctocog alfa as prophylactic treatment in a dose of 35±5 ME/kg 3 times per week during 21±1 weeks. Before participation in this clinical trial 2 pts had received treatment with another recombinant FVIII, 2 pts had therapy with pdFVIII and 8 pts had been treated with rFVIII and pdFVIII. The main criterion of drug efficacy was the incidence of spontaneous bleeding occurred within 48 hours after of the moroctocog alfa injection. The additional criteria were: · The severity of spontaneous bleeding occurred in 21 ± 1 week. · Number of injections needed for the one episode of bleeding according of its severity. · The total amount of drug administered over a period of prophylactic treatment and treatment "on demand". · The number of patients with severe hemophilia A with a residual activity of FVIII ≥1% in 48 hours after the injection on prophylactic therapy. During the follow up period (21±1 week) 17 bleeding episodes were registered, 2 of them (11,8%) were severe, 10 (58,8%) were moderate and 5 (29,4%) were mild (Tab.1). Number of bleeding episodes (spontaneous and traumatic) was 17 (1.55 in average). Number of spontaneous bleeding was 3 (17,6%), 1 of them was mild and 2 were moderate. The average number of injections that stop one bleeding episode was 1.7±0.8. The total amount of moroctocog alfa administered over a period was 1.502.000 ÌÅ for prophylactic treatment and 64.750 ÌÅ for "on demand" treatment. The number of patients with severe hemophilia A with a residual activity of FVIII ≥1% in 48 hours after injection on prophylactic therapy was 63,6% on visit 2, 90,09% on visit 3 and 81,1% on visit 4. The safety assessment was performed in 12 patients. There were 8 adverse events and 7 of them were not associated with drugs administration. There was one serious adverse effect, allergic reaction accompanied by arthralgia and cephalalgia. The patient was excluded from the trial without consequences for life and health. There were no infection transmissions and de novo inhibitor incident. The study showed that moroctocog alfa is effective and safe in prophylactic treatment and stopping of bleeding in adolescents with severe hemophilia A. Table 1. Efficacy evaluation Table 1. Efficacy evaluation Disclosures No relevant conflicts of interest to declare.

French Previously Untreated Patients with Severe Hemophilia A after Exposure to Recombinant Factor VIII : Incidence of Inhibitor and Evaluation of Immune Tolerance

1998 ◽  
Vol 80 (11) ◽  
pp. 779-783 ◽  
Author(s):  
Y. Laurian ◽  
E. P. Satre ◽  
A. Borel Derlon ◽  
H. Chambost ◽  
P. Moreau ◽  
...  
Keyword(s):  
Factor Viii ◽  
Immune Tolerance ◽  
Hemophilia A ◽  
High Titer ◽  
Recombinant Factor Viii ◽  
High Dose ◽  
Severe Hemophilia ◽  
Inhibitor Development ◽  
Intron 22 Inversion ◽  
Median Period

SummaryFifty French previously untreated patients with severe hemophilia A (factor VIII <1%), treated with only one brand of recombinant factor VIII (rFVIII), were evaluated for inhibitor development, assessment of risk factors and outcome of immune tolerance regimen. The median period on study was 32 months (range 9-74) since the first injection of rFVIII. Fourteen patients (28%) developed an inhibitor, four of whom (8%) with a high titer (≥10 BU). All inhibitor patients but one continued to receive rFVIII either for on-demand treatment or for immune tolerance regimen (ITR). Among these patients, inhibitor was transient in 2 (4%), became undetectable in 6 and was still present in 6. The prevalence of inhibitor was 12%. Presence of intron 22 inversion was found to be a risk factor for inhibitor development. Immune tolerance was difficult to achieve in our series despite a follow-up period of 16 to 30 months: immune tolerance was complete in only one out of the 3 patients undergoing low dose ITR and in one out of the 5 patients with high dose ITR.

scholarly journals Interim Analysis of the Extension Study with rVIII-SingleChain in Previously Untreated Patients (PUPs) with Severe Hemophilia A (CSL627-3001)

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 162-162
Author(s):  
Elena Santagostino ◽  
Kathelijn Fischer ◽  
Christoph Koenigs ◽  
Claudia Djambas Khayat ◽  
Samantha Lucas ◽  
...  
Keyword(s):  
Research Funding ◽  
Low Dose ◽  
Hemophilia A ◽  
High Titer ◽  
Severe Hemophilia ◽  
Bleeding Events ◽  
Safety And Efficacy ◽  
Inhibitor Development ◽  
On Demand ◽  
Peak Titer

Background: rVIII-SingleChain is a novel B-domain truncated recombinant Factor VIII comprised of covalently bonded FVIII heavy and light chains designed to have a high binding affinity to von Willebrand factor. Aims: This multicenter, open-label, phase III extension study investigates the safety and efficacy of rVIII-SingleChain for prophylaxis and on-demand treatment of bleeding episodes in 50 previously untreated patients (PUPs) for at least 50 Exposure Days (EDs). An ITI substudy was implemented to allow the use of rVIII-SingleChain to attempt inhibitor eradication for PUPs who develop an inhibitor to FVIII. Method: PUPs with severe hemophilia A (no prior exposure to any FVIII product, and endogenous Factor VIII &lt;1%) were assigned by the investigator to a prophylaxis or on-demand treatment regimen. Inhibitors were assessed monthly. Patients diagnosed with an inhibitor to FVIII (two consecutive central laboratory [CL] results of ≥0.6 BU/mL) could be enrolled into the ITI substudy or remain in the main study. The ITI substudy regimens are: 50 IU/kg 3x/week (low), 100 IU/kg daily (medium), or 200 IU/kg daily (high). Inhibitor eradication was defined as two consecutive CL results of &lt;0.6 BU/mL. One subject was withdrawn per protocol due to high titer inhibitor diagnosis prior to ITI substudy implementation. Results: As of March 28, 2019, 23 PUPs were treated with rVIII-SingleChain. Median age: 1 y (range 0-5). Mean (SD) time on study: 21.6 (12.6) months. Race distribution; Asian 2, Black 7, White 14. There have been 147 bleeding events treated with rVIII-SingleChain rated for hemostatic efficacy by the investigator. While patients were inhibitor negative, the overall treatment success (rating of excellent/good) was 93%, and the annualized spontaneous bleeding rate (AsBR) was 0.58. The adverse event profile was as expected, as the most frequently occurring adverse events were upper respiratory tract infections and inhibitors. Twelve subjects (52%) [95% CI 31%, 73%] were diagnosed with an inhibitor to FVIII; 6 (26%) high titer (peak titer ≥5 BU/mL), and 6 (26%) low titer (peak titer &lt;5 BU/mL). Seven of 11 inhibitor negative subjects achieved &gt;50 EDs, 1 achieved 47 EDs, and 3 achieved &lt;20 EDs. The median ED for inhibitor development (initial result) was 10, range 4-23. All PUPs enrolled had ≥1 risk factor for inhibitor development (Table 1) including genetic mutation, age of first exposure, initial treatment reason and assigned regimen, as well as bleeding events and infections; inhibitor positive and negative subjects were comparable. Of the 12 inhibitor positive subjects, 11 continued treatment with rVIII-SingleChain, 7 were treated with approximately 50 IU/kg 3x/week (low dose ITI), 3 with an increased prophylaxis regimen, 1 with no change in regimen, and 0 with high or medium dose ITI regimen (Table 2). Eight of 11 (73%) inhibitor positive subjects (2 high titer, 6 low titer) achieved eradication; 5 low titer subjects were eradicated within 6 months. The clinically relevant inhibitor subjects (2 high titer, and 1 persistent low titer) achieved eradication in a median of 15.7 months, 2 using low dose ITI, and 1 using increased prophylaxis. Eradicated patients were negative for a median of 13.6 months, and no inhibitor relapse was observed. Three remaining inhibitor positive patients are early in their rVIII-SingleChain inhibitor treatment (2.1, 3.5, and 5.4 months). Detailed analysis of the antibody signature was performed, and revealed epitope isotypes and subclass distribution comparable to other FVIII molecules. Conclusion: Overall, rVIII-SingleChain demonstrates a positive benefit:risk profile for safety and efficacy in PUPs. The crude high titer inhibitor rate is 26% which is consistent with other rFVIII products, whereas the crude low titer inhibitor rate is currently 26% which is on the higher end in comparison to other rFVIII products. Immunological analyses suggest a low affinity antibody population in subjects with low titer inhibitors. The majority of subjects (73%) who continued treatment with rVIII-SingleChain achieved eradication on a low dose ITI or prophylaxis regimen of approximately 50 IU/kg 3x/week or less. Additional time on study for the currently enrolled subjects is required to determine the final inhibitor and eradication rates in PUPs treated with rVIII-SingleChain. Disclosures Santagostino: Pfizer: Consultancy, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Shire / Takeda: Consultancy, Speakers Bureau. Koenigs:Roche: Consultancy; CSL Behring: Research Funding, Speakers Bureau; Bayer Vital GmbH: Research Funding, Speakers Bureau; Biotest AG: Research Funding, Speakers Bureau; Intersero: Research Funding; Grifols: Speakers Bureau; Pfizer: Research Funding, Speakers Bureau; Shire: Research Funding, Speakers Bureau; Sobi: Research Funding, Speakers Bureau. Djambas Khayat:Novo Nordisk: Consultancy, Speakers Bureau; Pfizer: Speakers Bureau. Lucas:CSL Behring: Employment. Salazar:CSL Behring: Employment. Brainsky:CSL Behring: Employment. Chung:CSL Behring: Employment. Goldstein:CSL Behring: Employment. Mahlangu:Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau; Spark: Consultancy, Honoraria, Research Funding, Speakers Bureau; Biomarin: Research Funding; Novartis: Research Funding; Pfizer: Research Funding; Sanofi: Research Funding; Unique: Research Funding; Catalyst Biosciences: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Honoraria, Research Funding, Speakers Bureau; Baxalta: Consultancy, Honoraria, Research Funding, Speakers Bureau; CSL Behring: Consultancy, Honoraria, Research Funding, Speakers Bureau.

scholarly journals Long-Term Safety and Efficacy Data of a Plasma-Derived Factor VIII Concentrate with von Willebrand Factor for Treatment of Patients with Hemophilia A Covering 18 Years

2019 ◽  
Vol 39 (04) ◽  
pp. 360-367 ◽  
Author(s):  
Sabine Friederike Karolin Kittler ◽  
Wolfgang Miesbach ◽  
Artur Bauhofer ◽  
Thomas Becker ◽  
Jörg Schüttrumpf ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Hemophilia A ◽  
High Titer ◽  
Age Groups ◽  
Real Life ◽  
Severe Hemophilia ◽  
On Demand ◽  
Von Willebrand ◽  
Willebrand Factor

AbstractWe describe the results of the (to our knowledge) longest long-term noninterventional study so far performed to obtain real-life data on the treatment of hemophilia A patients with a single plasma-derived FVIII concentrate containing von Willebrand factor (pdFVIII; Haemoctin/Faktor VIII SDH Intersero). A total of 198 patients (146 in Germany and 52 in Hungary), of whom 160 had severe and 38 nonsevere hemophilia A, representing all age groups (0–88 years; mean ∼25 years at inclusion) were analyzed during prophylactic or on-demand treatment over 18 years (overall 1,418 patient-years; mean >7 years). pdFVIII was very effective and well tolerated. The mean annual bleeding rate, including spontaneous and traumatic bleeds, was considerably lower for patients treated prophylactically (mean 5.4; median 3.1) than for patients treated on demand (mean 26.1; median 21.9). Inhibitors were found in 13% (3/23) and high-titer inhibitors in 4% (1/23) of previously untreated patients with severe hemophilia A. Four previously treated patients with severe hemophilia A developed inhibitors, thereof three high-titer inhibitors (3.3 and 2.5 high-titer inhibitors in 1,000 patient-years). No unexpected adverse effect on the health of the patients, no pdFVIII-related thrombosis, thromboembolic event, or hypersensitivity reaction, and no suspected viral transmission related to pdFVIII were documented.

Effects of “Primary Prophylaxis” and “On-Demand” Therapy on the Clinical Expression of Severe Hemophilia A in Children - Results of a Multicenter Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3146-3146
Author(s):  
Rosemarie Schobess ◽  
Karin Kurnik ◽  
Wolfhart Kreuz ◽  
Frauke Friedrichs ◽  
Anne Krumpel ◽  
...  
Keyword(s):  
Hemophilia A ◽  
Bleeding Episode ◽  
Joint Damage ◽  
Primary Prophylaxis ◽  
Secondary Prophylaxis ◽  
Outcome Variable ◽  
Severe Hemophilia ◽  
On Demand ◽  
Imaging Results ◽  
Bleeding Episodes

Abstract Background: Patients with severe hemophilia A (HA) can either be treated by regular FVIII infusions twice or thrice per week (prophylaxis), or only in case of bleeding episodes (on-demand). Whereas prophylaxis reduces the number of bleeding episodes and may therefore prevent the development of hemophilic arthropathy, recommendations regarding age and dose at start of prophylactic regimens are still a matter of debate. The present cohort study was performed to investigate the role of “primary prophylaxis” versus “on-demand” therapy in HA children. The outcome variable was imaging-proven hemophilic joint damage. Methods: 42 children were initially treated with primary prophylaxis following the first bleeding episode, and were frequency-matched (year of birth, catchment area) to 67 patients receiving “on-demand” therapy with an early switch to “secondary prophylaxis”. Results: In multivariate analysis adjusted for the HA mutation type and the presence or absence of thrombophilia, the Pettersson score investigated at a median age of 12.5 years in joints with at least one documented bleeding episode was no significantly different between the two patient groups (p=0.944), and no statistically significant differences were found in patients with target joints (p=0.3), or in children in which synovitis had occurred (p=0.77). Imaging results obtained showed a substantial agreement (87.14%) beyond that expected by chance alone (42.4%) between local and central readers in the patients tested (kappa=0.77; Z= 17.27; p < 0.001). Conclusion: In cases with severe HA where primary prophylaxis is impossible, the procedure to switch from “on-demand” to early secondary prophylaxis can be achieved in the majority of young children affected. In addition, the needs of parents around the time of diagnosis of severe HA could be better addressed.

Effect on Joint Health of Routine Prophylaxis with Bayer’s Sucrose-Formulated Recombinant Factor VIII (rFVIII-FS) in Adolescents and Adults Previously Treated on Demand: MRI Analyses from the 3-Year Spinart Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2854-2854 ◽  
Author(s):  
Bjorn Lundin ◽  
Walter Hong ◽  
David Raunig ◽  
Sylvia Engelen ◽  
Charles Peterfy ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Factor Viii ◽  
Structural Damage ◽  
Hemophilia A ◽  
Severe Hemophilia ◽  
On Demand ◽  
Routine Prophylaxis ◽  
Bayer Healthcare ◽  
Adolescents And Adults ◽  
Bleeding Episodes

Abstract Introduction: The benefits of primary prophylaxis with a factor VIII (FVIII) product in pediatric patients with severe hemophilia A are well established. Fewer data are available on the benefits of secondary prophylaxis (started after ≥2 joint bleeds but before the onset of documented joint disease). The 3-year SPINART study compared the efficacy and safety of routine prophylaxis vs on-demand treatment in adolescents and adults with severe hemophilia A, all of whom were treated with Bayer's sucrose-formulated recombinant FVIII (rFVIII-FS). Primary 3-year data on magnetic resonance imaging (MRI) joint assessments in SPINART have been recently reported. Here we present additional analyses of the SPINART 3-year MRI data. Methods: SPINART was a 3-year, randomized, controlled, parallel-group, open-label study conducted at 31 centers in the United States, Bulgaria, Romania, and Argentina. Male patients aged 12–50 years were eligible for SPINART if they had severe hemophilia A (FVIII:C <1%), ≥150 exposure days to any FVIII product, no current evidence or history of FVIII inhibitors, no prophylaxis for >12 consecutive months in the past 5 years, and 6–24 documented bleeding events or treatments in the previous 6 months. Eligible patients were randomly assigned 1:1 to on-demand treatment or prophylaxis. Patients assigned to prophylaxis received rFVIII-FS 25 IU/kg 3 times weekly; in patients with ≥12 bleeding episodes per year, dose increases of 5 IU/kg were permitted at years 1 and 2. All patients underwent MRI assessments at baseline and year 3 to evaluate the structure of 6 index joints (knees, ankles, elbows). Each MRI was read by 3 radiologists blinded to treatment assignment who independently completed the Extended MRI (eMRI) scale. The eMRI scale has 2 domains (soft tissue, osteochondral), and total eMRI scores range from 0 to 45 based on soft-tissue domain scores of 0 to 9 and osteochondral domain scores of 0 to 36; higher eMRI scores indicate greater joint structural damage. Change from baseline to year 3 in eMRI total score based on all 6 index joints was analyzed for the following baseline characteristics: region (US vs non-US), age (≤29 vs >29 years), and number of bleeding episodes in the previous 6 months (<8 vs ≥8). For patients with target joints, change from baseline to year 3 in eMRI scores in the worst target joint was analyzed using analysis of covariance adjusted for bleeding frequency during the prior 6 months. Results: Eighty-four patients (42 per treatment group) were enrolled in the SPINART study. Target joint analysis data for patients with target joints who completed the study were available for 28 on-demand and 20 prophylaxis patients. Least squares (LS) mean change from baseline to year 3 in eMRI total score in the analyzed target joint was 0.91 (95% CI, –0.06 to 1.88) and 1.09 (95% CI, 0.12–2.07) for the on-demand and prophylaxis groups, respectively; the difference was not statistically significant (LS mean difference, 0.18; 95% CI, –1.05 to 0.70; P=0.68). Results for the subgroup analyses are shown in the Table. Table.eMRI Total Score (Mean ± SD Change From Baseline to Year 3)Region Age, y Number of Bleeds in Past 6 MonthsUSNon-US≤29 >29 <8≥8On demand0.56±0.77 (n=14)1.24±1.35 (n=16)1.34±1.21 (n=18)0.29±0.70 (n=12)0.88±0.83 (n=4)0.93±1.20 (n=26)Prophylaxis1.05±1.36 (n=10)0.61±1.70 (n=22)0.46±1.88 (n=17)1.08±1.15 (n=15)0.91±0.69 (n=11)0.67±1.91 (n=21) Conclusions: Over 3 years of treatment, change in eMRI total score for target joints was similar for the on-demand and prophylaxis groups in SPINART. In the prophylaxis group, progression of joint structural damage after 3 years of treatment, as indicated by changes in eMRI total scores based on all 6 index joints, did not differ by number of bleeding episodes in the preceding 6 months but appeared to be less pronounced among younger patients compared with older patients and among those in the non-US group compared with the US group; results by age and region in the on-demand group were opposite of those seen in the prophylaxis group. These results must be interpreted with caution given the small patient numbers, the possibility that the study duration was not sufficient to show changes on MRI, and the fact that target joints were assessed. These results may underscore the importance of preventing target joint development and show that once a target joint has developed, MRI may not show reversal of pre-existing damage despite prophylaxis. Disclosures Lundin: Bayer: Received reimbursement from Bayer for symposium attendance, Received reimbursement from Bayer for symposium attendance Other; Bayer HealthCare : Employed by the Center for Medical Imaging and Physiology at Skåne University Hospital and is under contract to Bayer HealthCare for work performed for SPINART Other. Hong:Bayer HealthCare: Employment. Raunig:Employed by ICON Medical Imaging and is under contract to Bayer HealthCare for work performed for SPINART on the validation of the eMRI scale and Colorado Adult Joint Assessment Scale.: Consultancy. Engelen:Bayer HealthCare: Employment. Peterfy:Spire Sciences, Inc.: Owner of Spire Sciences, Inc., which provides central image analysis services to pharmaceutical and medical device companies. Other. Werk:Bayer HealthCare: Under contract to Bayer HealthCare for work performed for SPINART. Other. Manco-Johnson:Bayer: Membership on an entity's Board of Directors or advisory committees.

A large deletion, spanning exons 1 to 25 of F8 gene, and a high‐titer factor VIII inhibitor, in severe hemophilia A

2020 ◽  
Vol 42 (3) ◽  
Author(s):  
Sayed Hamid Mousavi ◽  
Seyed Alireza Mesbah‐Namin ◽  
Sirous Zeinali ◽  
Mohammad Jazebi ◽  
Ali Dabbagh ◽  
...  
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
High Titer ◽  
Large Deletion ◽  
Factor Viii Inhibitor ◽  
Severe Hemophilia ◽  
Viii Inhibitor

Prophylactic Dosing of Anti-Inhibitor Coagulant Complex (FEIBA) Reduces Bleeding Frequency In Hemophilia A Patients with Inhibitors: Results of the Pro-FEIBA Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 720-720 ◽  
Author(s):  
Cindy A. Leissinger ◽  
Eric Berntorp ◽  
Chiara Biasioli ◽  
Shannon Carpenter ◽  
Hyejin Jo ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Allergic Reaction ◽  
Board Of Directors ◽  
Research Funding ◽  
Hemophilia A ◽  
Study Drug ◽  
Advisory Committees ◽  
Patient Age ◽  
On Demand ◽  
Bleeding Episodes

Abstract Abstract 720 Patients with congenital hemophilia and inhibitors are at increased risk for serious bleeding complications and progression to end-stage joint disease. Anecdotal reports and small case series suggest that regular doses of anti-inhibitor coagulant complex (AICC; FEIBA VH) may be effective in preventing bleeding episodes in patients with hemophilia A and inhibitors. The Pro-FEIBA study is the first prospective controlled clinical trial to study the efficacy of AICC in bleed prevention. Study Population and Design: The study was conducted in hemophilia A patients >2 years with a history of high-titer inhibitors who were using bypassing therapy for the treatment of bleeding episodes. Subjects on or planning immune tolerance therapy were excluded as were patients with thrombocytopenia or other bleeding disorders. This randomized, crossover study compared 6 months of AICC prophylactically dosed at 85 U/kg ± 15% on 3 nonconsecutive days per week (Prophy period) to 6 months of on-demand therapy (OD period) (target dose for the treatment of bleeds: 85 U/kg ± 15%). The 2 study periods were separated by a 3-month washout, during which time patients used on-demand therapy for bleeding. Patients were randomized to initially enter either the 6-month Prophy period or the 6-month OD period. Each patient then crossed-over to the alternate study period after a 3-month wash-out. Results: Thirty-four subjects were randomized; 26 subjects completed both study periods and were deemed evaluable per protocol (PP) for efficacy analysis of the primary outcome to compare bleeds in each 6-month treatment period. Eight subjects did not complete the study (1 patient in the Prophy treatment arm and 1 patient in the post-prophylaxis washout period died of complications associated with underlying illness and bleeding, 1 patient experienced an allergic reaction to study drug, 1 patient was lost to follow-up, and 4 patients withdrew from study). All randomized subjects were evaluated for safety. In the PP group, mean patient age was 26.9 years (median: 24.7; range: 2.8–67.9). In the total randomized group, mean patient age was 27.1 years (median: 28.7; range: 2.8–67.9). Of the 26 subjects who completed the study PP, 14 were randomized to enter the Prophy period first and then crossed-over to the OD period, while 12 subjects were initially randomized to enter the OD period and then crossed-over to the Prophy period. For the PP analysis, total bleeds and joint bleeds requiring treatment during the 2 study periods were compared (p-value is for the Wilcoxon signed-rank test of difference between OD and Prophy periods). In addition, bleeds for the 6-month period prior to enrollment were recorded retrospectively on study entry. Efficacy: Both total bleeds and joint bleeds were significantly reduced during the Prophy period as compared with the OD period (p < .0001) Table 1. There was no difference in bleed event rates based on randomization sequence (ie, no carry-over effect was detected when the Prophy period preceded the OD period). Safety: A total of 38 serious adverse events (SAEs) occurred, none of which was thrombotic in nature. One SAE was deemed by the study safety monitor to be related to the study drug (an allergic reaction). Otherwise, treatment was safe and well tolerated. Conclusion: These results in patients with hemophilia A and inhibitors show that AICC, dosed at 85 IU/kg +/&minus; 15% given on 3 non-consecutive days each week was associated with a 62% reduction in all bleeds and a 61% reduction in joint bleeds as compared with on-demand therapy. Disclosures: Leissinger: Baxter: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; NovoNordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Off Label Use: This is a report of a clinical trial using the Anti-Inhibitor Coagulant Complex, FEIBA, as prophylactic therapy to prevent bleeding in hemophilia patients with inhibitors. FEIBA is not currently licensed for use in prophylaxis in the US. Berntorp:Baxter: Consultancy, Honoraria, Research Funding. Negrier:Baxter: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Rocino:Baxter: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; NovoNordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Windyga:Baxter: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Gringeri:Baxter: Consultancy, Honoraria, Research Funding; NovoNordisk: Honoraria.

Prophylaxis in Patients with Hemophilia a and Its Impact on Quality of Life Using the Specific Index Haem-a-Qol at a Hospital in Paraguay

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4959-4959
Author(s):  
Cristobal A Frutos ◽  
Barbara Konkle ◽  
Jorge Batista ◽  
Silvia Brizuela ◽  
Elvira Enciso ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Physical Health ◽  
Prophylactic Treatment ◽  
Hemophilia A ◽  
Minor Trauma ◽  
Severe Hemophilia ◽  
On Demand ◽  
Bleeding Episodes ◽  
The Impact

Abstract Prophylactic replacement therapy with FVIII is considered the standard of care for patients with hemophilia although a protocol for administering the prophylaxis has yet to be defined by the World Federation of Hemophilia. Gaona in 2012 demonstrated a significant reduction in the number of hospitalizations due to bleeding episodes in patients with Hemophilia A treated with secondary prophylaxis at the Hematology Service of the Hospital Central del Instituto de Prevision Social (HCIPS) with a regimen of 25 IU/Kg per week in two infusions by reporting results from such regimen that had started at the HCIPS in 2010. This is a lower dose to those most frequently used in high resource countries like the Malmo or Utrecht protocols. The goal of this study was to assess the impact of our lower dose prophylaxis regimen on bleeding events, hospitalizations and quality of life as an alternative for low resource countries that cannot afford to provide their patients with higher dose treatments. The Dutch group Haemo-QoL designed the specific questionnaire for adult patients with hemophilia, the Haem-A-QoL with a Spanish version available for patients aged 17 and up. Results: The HCIPS currently has 36 patients receiving prophylactic treatment with FVIII. From these 18 patients consented to filling out the questionnaire. The mean age of the patients was 28. 3 of the patients were married, 2 were in a stable relationship and 13 were single. 62% of patients lived within 20 km of the Hospital and 38% lived further away going up to 200 km. 17 of the 18 patients had the highest level of education possible for their age. Only one patient, the oldest one, had stopped his education at primary school. All of them had severe disease with one or more affected joints. The average FVIII use per year was 68,000 IU ranging from 8,000 IU to 96,000 IU or 917 IU/kg/year. The strongest determinant for receiving less FVIII was missing appointments. Distance to the Hospital was not of significance. Bleeding episodes prior to prophylactic treatment was 2-3 minor traumatic bleeding episodes per week (after brushing their teeth, easy bruising from minor trauma), 2-3 joint bleeds per month at which point they would seek medical assistance and 1-2 major bleeding episodes per year requiring hospitalization. In the last year 5 patients were hospitalized once. One for pneumonia, one for phlebitis, one for dengue fever and two for hemathrosis. They reported a decrease in bleeding episodes at home from 2-3 joint bleeds per month to 1 every other month. Patients reported after traumatic events their bleeding was "normal" (i.e. when brushing their teeth if they started bleeding they would continue bleeding for days at a time whereas when in prophylaxis they would bleed right after the brushing and then it stopped which they took to be normal). Converting the results from the Haem-A-QoL questionnaire to a scoring system of 1-100 being 1 the best QoL and 100 the worst, the average QoL was 52. With scores of 60 for physical health, 50 for feelings, 52 for view of themselves, 48 for work/school, 53 for treatment, 56 for future, 47 for family planning and 45 for dating. Scores for sports and leisure though only amounting to 64, 33% of patients said that category did not apply to them since they did not practice any sports and the dealing category with a score of 37 was the lowest of all. When compared to results published by a Blood Center in Brazil with an on demand regimen patients with severe hemophilia in that study showed a physical health score of 55, 40 for feelings, 35 for self-perception, 60 for sports and leisure, 35 for work and school, 20 for coping, 45 for treatment, 45 for future and 25 for dating with an average overall score of 40. With an annual average usage of 63,683 IU on the severely affected patients. In summary, the proposed dosing of 25IU/kgs/week seems at first glance to reduce bleeding episodes among patients with severe hemophilia as well as hospitalizations. In general patients treated at the HCIPS have a regular to poor quality of life as measured by the Haem-A-QoL questionnaire which contrasts with results from the Brazilian study on quality of life from patients with on demand treatment and roughly same FVIII usage per year showing their patients with severe hemophilia had an overall quality of life from regular to good. Perhaps the psychological factor comes in to play? A follow up study after patients receive proper psychological evaluations may help clarify results. Disclosures No relevant conflicts of interest to declare.

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