Limited Generalizability of a Retrospective Chart Review Comparing 3 Recombinant FVIII Products for Hemophilia A Prophylaxis

Introduction. Advances in hemophilia care and treatment have led to increases in the life expectancy among hemophiliacs. As a result, persons with hemophilia are reaching an older age and experiencing various age-related health conditions never seen before in this population.Aim. To determine the prevalence of comorbidities among middle-aged and elderly hemophilia A and hemophilia B patients.Methods. Retrospective chart review among all hemophilia patients, who attended the Gulf States Hemophilia and Thrombophilia Center.Results. All patients had at least one comorbid condition other than hemophilia, and the majority had between 3 and 6 comorbidities. The most common conditions identified were chronic hepatitis C, hypertension, HIV, chronic arthropathy, and overweight/obesity.Conclusions. Since persons with comorbidities are more likely to have poorer health outcomes and require greater care in managing their health needs, caring for aging hemophiliacs is likely to pose various social and economic challenges for both patients and providers.

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Safety and Efficacy Profile of rAHF-PFM for Immune Tolerance Induction as Assessed In 3 Clinical Trials (PUP ITI, PRE-PAIR, and PAIR).

Blood ◽

10.1182/blood.v116.21.3670.3670 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3670-3670

Author(s):

Gerald Spotts ◽

Brigitt E. Abbuehl ◽

Huong D. Luu ◽

Clara K. Song ◽

Jacqueline A. Dyck-Jones ◽

...

Keyword(s):

Safety Assessment ◽

Chart Review ◽

Hemophilia A ◽

Retrospective Chart Review ◽

Severe Hemophilia ◽

Success Rates ◽

Plasma Albumin ◽

Safety And Efficacy ◽

Antihemophilic Factor ◽

Partial Success

Abstract Abstract 3670 Introduction: Development of neutralizing antibodies to FVIII is the most serious complication in the management of hemophilia A today. Eradication of the inhibitor with ITI therapy is a common treatment practice however, there are few reports of controlled studies, and much of the current ITI experience is reported from international registries and small site-based case studies. A previous case-series demonstrated successful tolerance in 9/12 (75%) patients using ADVATE [Antihemophilic Factor (Recombinant) Plasma/Albumin Free Method] (rAHF-PFM). Data on the safety and efficacy of rAHF-PFM in ITI therapy have now been formally captured in the recently completed Previously Untreated Patient (PUP-ITI) study, a retrospective chart review (PRE-PAIR), and an ongoing Prospective ADVATE ITI Registry (PAIR). Objectives: To provide a critical assessment of the safety and efficacy of rAHF-PFM in ITI therapy through a review of the cumulative data from PUP-ITI, PRE-PAIR, and PAIR. Methods: PUP study was a prospective, multicenter, open-label, clinical study in PUPs <6 years of age with severe or moderately severe hemophilia (FVIII level ≤2%) who underwent on-demand or prophylactic treatment with rAHF-PFM. Subjects who developed inhibitors against rAHF-PFM could enter the PUP-ITI study and receive ITI. PRE-PAIR was a multicenter, retrospective, chart review of PTPs of any age and any severity of hemophilia A with history of ITI with rAHF-PFM. PAIR is an ongoing non-interventional safety surveillance registry of subjects prescribed rAHF-PFM for ITI. In all three studies, the choice of ITI regimen was at the discretion of the investigator; however, for the PUP-ITI study, the ITI regimen was based on site-specific ITI data and/or institutional guidelines, or as described in peer reviewed literature. The primary endpoints for PUP-ITI and PRE-PAIR were the success rate of ITI. The PAIR report was an interim safety assessment that did not examine efficacy endpoints. For PUP-ITI and PRE-PAIR, the definitions of success required the subject to have achieved 2 consecutive negative inhibitor test results and if data available, demonstrated normalized FVIII recovery. For PRE-PAIR, partial success was defined as achieving negative titer but without normalized recovery. Results: In PUP-ITI, a total of 11 subjects initiated ITI; 3 withdrew and 8 completed ITI. In PRE-PAIR, 35 subjects were enrolled, 30 of which were evaluable per protocol. Of these 30 subjects, 20 had moderately severe to severe hemophilia A (FVIII ≤2%), and high-titer (>5 BU) inhibitor. As of Sept 4, 2010, 18 subjects had been enrolled in PAIR and were included in an interim safety assessment. Over all 3 studies, most commonly prescribed initial dose regimen in subjects with high inhibitor titer prior to initiation of ITI was 100 IU/kg QD (17/37 [46%]), followed by 200 IU/kg QD (11/37 [30%]), and any dose at a frequency of <1/day (9/37 [24%]). In the low titer inhibitor subjects the most commonly prescribed regimen were various doses with a frequency of <1/day (13/22 [59%] subjects). Of the 11 subjects in the PUP study who participated in the PUP-ITI study, 3 withdrew and 8 (72.7%) achieved success (95% CI: 43.4%, 90.3%). All 8 subjects (100%) achieved success, with 1st negative titer at a median time of 1.8 months (0.0 - 4.1 months) and the 2nd negative titer at 3.0 months (1.1 – 9.0 months). In PRE-PAIR, sum of complete and partial success rates gave a total success rate of 76.7% (23/30) in subjects who met inclusion criteria (95% CI: 59.1, 88.2%). During these 3 studies, there were no SAEs related to rAHF-PFM ITI therapy and 6 non-serious AEs in 3 subjects considered to be related to rAHF-PFM (diarrhea, vomiting, pain following bleed, mild urticaria, and mild fever). Conclusions: In 2 clinical studies of rAHF-PFM therapy in ITI treatment, rAHF-PFM was found to be efficacious in a variety of dosing regimens reflective of current standards of practice in hemophilia care. Overall success rates ranged from 72.7% in PUP-ITI to 76.7% in PRE-PAIR. Success rates in these 2 rAHF-PFM studies are similar to those reported in published literature. In all 3 ITI studies, there were no product related SAEs and 6 non-serious AEs in 3 subjects considered to be related to rAHF-PFM, suggesting that rAHF-PFM used for ITI has a similar risk profile established in routine clinical use. These data suggest that ITI treatment with rAHF-PFM was both effective and safe. Disclosures: Spotts: Baxter Bioscience: Employment. Off Label Use: ADVATE [Antihemophilic Factor (Recombinant) Plasma/Albumin Free Method] (rAHF-PFM)use in ITI therapy. Abbuehl:Baxter Bioscience: Employment. Luu:Baxter Bioscience: Employment. Song:Baxter Bioscience: Employment. Dyck-Jones:Baxter Bioscience: Employment. Guzman-Becerra:Baxter Bioscience: Employment. Wu:Baxter Bioscience: Employment. Oh:Baxter Bioscience: Employment. Zoerer:Baxter Bioscience: Employment. Sosa:Baxter Bioscience: Employment. Stephens:Baxter Bioscience: Employment. Yamamoto:Baxter Bioscience: Employment. Ewenstein:Baxter Bioscience: Employment.

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Cardiovascular Comorbidities in a United States Patient Population with Hemophilia a: A Comprehensive Chart Review

Blood ◽

10.1182/blood.v128.22.4966.4966 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4966-4966

Author(s):

Jennifer Pocoski ◽

Brittny Rule ◽

Augustina Ogbonnaya ◽

Lois Lamerato ◽

Michael Eaddy ◽

...

Keyword(s):

Risk Factors ◽

Arterial Thrombosis ◽

Research Funding ◽

Chart Review ◽

Hemophilia A ◽

Small Sample Size ◽

Retrospective Chart Review ◽

Small Sample ◽

Control Group ◽

Control Cohort

Abstract Introduction: Two previous retrospective claims database analyses (Pocoski J, et al. Haemophilia. 2014;20(4):472-478 and Humphries TJ, et al. Am J Hematol. 2016;91(5):E298-299) reported increased prevalence and earlier onset of cardiovascular (CV) comorbidities in patients with vs without hemophilia A (HEM A). Because of many known limitations of claims databases, a comprehensive chart review at a large integrated delivery network was conducted to assess differential CV comorbidities. Aim: This study was designed to confirm the previous findings on CV risk factors and associated diseases in 2 large claims databases of male patients with HEM A in the United States. Methods: This was a retrospective chart review study conducted at the Henry Ford Health System in patients diagnosed with HEM A (n=74) and matched Control patients (3:1) without a diagnosis of HEM A (Control, n=222). Baseline demographics, bleeding events, treatment parameters, co-existing diseases, hemophilia-associated events, and the prevalence of 12 CV risk factors and associated diseases were compared between the HEM A and Control cohorts. P values generated from a chi-square test for categorical variables and a t test for continuous variables were reported. To address the small sample size, statistical differences between the cohorts were also assessed using absolute standardized difference (SDiff), where a value ≥0.10 was considered statistically meaningful. Results: The Control cohort was well matched to the HEM A group by age, race, healthcare payer, and study year. As expected, the prevalence of hepatitis B and C, hepatocellular carcinoma, and HIV/AIDS was much higher in the HEM A cohort. Gastrointestinal, intracranial, muscle, and joint bleeds occurred only in HEM A patients. Bleeds of various types were recorded in 35 HEM A patients vs 1 in the Control group. HEM A was severe in 52.7% of patients, moderate and mild in 10.8% each, and unknown in 25.7%. The prevalence of hypertension, diabetes, obesity, hyperlipidemia, coronary artery disease, heart failure, stroke, venous and arterial thrombosis, ventricular arrhythmias, atrial fibrillation, and chronic renal disease was numerically higher in the Control cohort, but differences were statistically significant (P≤0.05) for diabetes and hyperlipidemia only. Statistical significance using SDiff was not reached for venous and arterial thrombosis and atrial fibrillation. Conclusions:The results of this retrospective chart review did not confirm diffuse statistically significant differences in CV comorbidities and their earlier onset in HEM A vs Controls. Reasons for the lack of confirmation are not clear but may include differences in methodology and patient populations among the studies. The Control group in this current study may have a greater medical burden than in the published studies. Our current results suggest numerically higher comorbidities in Controls for most variables. The conclusions of this study are limited by the small sample size of the hemophilia cohort and a potential selection bias associated with identification of the Control cohort. Disclosures Pocoski: Bayer: Employment. Rule:Bayer: Employment. Ogbonnaya:Takeda: Research Funding. Lamerato:Amgen, Inc.: Research Funding. Lunacsek:Bayer: Research Funding. Humphries:Bayer: Employment.

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Prevalence of Inhibitors in a Population of 3435 Hemophilia Patients in France

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648507 ◽

1992 ◽

Vol 67 (06) ◽

pp. 600-602 ◽

Cited By ~ 85

Author(s):

Y Sultan ◽

Keyword(s):

Hemophilia A ◽

Hemophilia B ◽

Study Group ◽

Cooperative Study ◽

Population Prevalence ◽

French Study ◽

Number Of Patients ◽

High Incidence ◽

Recombinant Fviii ◽

High Responders

SummaryA cooperative study between the 37 centers of the French Hemophilia Study Group was undertaken to establish the prevalence of inhibitor patients in the French hemophilia population. The prevalence reported in the literature varies widely from 3.6% to 17.5%. Some of the studies are dealing with a small number of patients and inhibitor patients are reported either to the total number of hemophiliacs or to the severely affected ones. The French study provided information concerning 3,435 hemophiliacs and showed a prevalence of 6.2% for the overall population. Prevalence of inhibitors was found to be 7% in the population of hemophilia A patients and 12.8% in the population of severely affected ones. The prevalence of inhibitors in the population of hemophilia B patients was 2% and 4% in the population of severely affected hemophilia B patients. The cooperative study also showed that 47.5% of inhibitors are detected before 10 years of age and that 82% of inhibitor patients are high responders. Analysis of inhibitor detection in patients under the age often showed that there was a peak in the population of 2 years old children. Although not comparable to the present study the high incidence of inhibitors with ultrapurified and recombinant FVIII reported in previously untransfused patient may be borne in mind.

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A Multicenter Pharmacosurveillance Study for the Evaluation of the Efficacy and Safety of Recombinant Factor VIII in the Treatment of Patients with Hemophilia A

Thrombosis and Haemostasis ◽

10.1055/s-0038-1665410 ◽

1997 ◽

Vol 78 (05) ◽

pp. 1352-1356 ◽

Cited By ~ 45

Author(s):

Emel Aygören-Pürsün ◽

Inge Scharrer ◽

Keyword(s):

Factor Viii ◽

Hemophilia A ◽

Parvovirus B19 ◽

Subjective Evaluation ◽

Recombinant Factor Viii ◽

Fviii Inhibitor ◽

Previously Treated Patients ◽

Previously Treated ◽

Bleeding Episodes ◽

Recombinant Fviii

SummaryIn this open multicenter study the safety and efficacy of recombinant factor VIII (rFVIII) was assessed in 39 previously treated patients with hemophilia A (factor VIII basal activity ≤15%).Recombinant FVIII was administered for prophylaxis and treatment of bleeding episodes and for surgical procedures. A total of 3679 infusions of rFVIII were given. Efficacy of rFVIII as assessed by subjective evaluation of response to infusion and mean annual consumption of rFVIII was comparable to that of plasma derived FVIII concentrates. The incremental recovery of FVIII (2.4 ± 0,83%/IU/kg, 2.12 ± 0.61%/IU/kg, resp.) was within the expected range. No clinical significant FVIII inhibitor was detected in this trial. Five of 16 susceptible patients showed a seroconversion for parvovirus B19. However, the results are ambiguous in two cases and might be explained otherwise in one further case. Thus, in two patients a reliable seroconversion for parvovirus B19 was observed.

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