scholarly journals Patient satisfaction and acceptability of an on-demand and on-prophylaxis device for factor VIII delivery in patients with hemophilia A

2019 ◽  
Vol Volume 13 ◽  
pp. 233-240 ◽  
Author(s):  
Giovanni Di Minno ◽  
Elena Santagostino ◽  
Massimo Morfini ◽  
Cosimo Ettorre ◽  
Dorina Cultrera ◽  
...  
Keyword(s):  
Patient Satisfaction ◽  
Factor Viii ◽  
Hemophilia A ◽  
On Demand

scholarly journals Factor VIII Use in the Treatment of Breakthrough Bleeds in Hemophilia A Patients without Inhibitors on Emicizumab Prophylaxis: The Phase 3 HAVEN 3 Study Experience

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2395-2395
Author(s):  
Michael Callaghan ◽  
Benjamin Trzaskoma ◽  
Richard H. Ko ◽  
Lucy Lee ◽  
Anisha M. Patel ◽  
...  
Keyword(s):  
Factor Viii ◽  
Exposure Time ◽  
Cumulative Dose ◽  
Research Funding ◽  
Hemophilia A ◽  
Phase 3 ◽  
Breakthrough Bleeding ◽  
On Demand ◽  
Equity Ownership ◽  
The Individual

Introduction HAVEN 3 was a phase 3 study investigating the use of emicizumab as prophylaxis in adult and adolescent (≥12 years old) persons with hemophilia A (PwHA) without factor VIII (FVIII) inhibitors (NCT02847637; Mahlangu et al. 2018). HAVEN 3 demonstrated that emicizumab prophylaxis once weekly or every two weeks was safe and highly effective in bleed prevention. The primary analysis of HAVEN 3 included an intrapatient comparison of 48 participants who received FVIII prophylaxis in a non-interventional study (NIS) prior to enrollment in HAVEN 3. Compared with emicizumab prophylaxis during the HAVEN 3 study, emicizumab prophylaxis resulted in an annualized bleed rate that was 68% lower than the rate with previous FVIII prophylaxis (1.5 vs 4.8, p<0.001). No dosing guidance was provided regarding the use of on-demand FVIII in HAVEN 3, and investigators prescribed FVIII at their own discretion. In this subsequent analysis, we characterize the dose and frequency of replacement FVIII used for the treatment of breakthrough bleeding in these 48 participants. Methods The primary comparisons in our analyses are focused on on-demand FVIII use for breakthrough bleeding while participants were on FVIII prophylaxis during the NIS versus its use while on emicizumab prophylaxis during HAVEN 3. Any use of on demand FVIII other than to manage breakthrough bleeding (e.g. prior to activity) was not included in our analyses. Given that, collectively, the total exposure time to emicizumab during HAVEN 3 was more than twice the exposure time to FVIII prophylaxis during the NIS (75.8 vs 28.6 years respectively), any treatment comparisons are drawn on an annualized basis. Annualized on-demand FVIII use was calculated by dividing by the number of days in the efficacy period and multiplying the resulting daily consumption by 365.25 days. The number of infusions and cumulative doses of on-demand FVIII use are described at the participant level as well as at the individual bleed level and are presented descriptively for both the NIS and HAVEN 3 exposure periods. No formal statistical inferences (i.e. calculation of p-values) have been conducted. All analyses were based on an October 2018 data cutoff. Results A total of 48 participants who were treated with FVIII prophylaxis during the NIS were then treated with emicizumab prophylaxis during HAVEN 3 and thus make up the total cohort for our analyses. Annualized infusion rates of on-demand FVIII per participant and cumulative doses of on-demand FVIII (in international units [IU] per kilogram) per participant were higher during the FVIII prophylaxis period when compared with the emicizumab exposure period (mean 15.3 vs 7.2; median 3.6 vs 0.6 annual infusions per participant and mean 602.4 IU/kg vs 209.0 IU/kg; median 75.5 IU/kg vs 19.1 IU/kg, respectively). At the individual bleed level, FVIII infusions and total cumulative dose suggested that participants were administered a similar amount of medication to treat bleeds during both the NIS and HAVEN 3 study periods: median number of infusions per bleed were 1.0 (interquartile range [IQR]=1.0) versus 2.0 (IQR=3.0) and median cumulative doses were 43.5 (IQR=35.1) versus 50.0 (IQR=72.7) IU/kg, respectively (Table 1). Conclusions This analysis revealed a lower annualized infusion rate and a correspondingly lower annualized cumulative dose of FVIII for treatment of breakthrough bleeds during emicizumab prophylaxis compared with FVIII prophylaxis. At the individual bleed level, the amount of on-demand FVIII used per bleeding episode was comparable between NIS and HAVEN 3 exposure periods. Thus, based on this single analysis, it appears that patients received less on-demand FVIII during emicizumab prophylaxis compared with FVIII prophylaxis, as a result of overall reduction of bleed frequency, while the treatment of individual bleeds appeared similar regardless of the prophylaxis therapy administered. Disclosures Callaghan: Octapharma: Consultancy; Novonordisk: Consultancy, Speakers Bureau; Global Blood Therapeutics: Consultancy; Sanofi: Consultancy; Takeda: Consultancy, Research Funding; Bayer: Consultancy, Speakers Bureau; Alnylum: Equity Ownership; Biomarin, Bioverativ, Grifols, Kedrion, Pfizer, Roche/Genentech, Shire, and Spark Therapeutics: Consultancy; Roche/Genentech: Speakers Bureau; Shire/Takeda: Speakers Bureau; Pfizer: Research Funding; Roche: Research Funding. Trzaskoma:Genentech: Employment, Equity Ownership. Ko:Genentech, Inc.: Employment. Lee:Genentech, Inc.: Employment. Patel:Genentech: Employment; Roche/Genentech: Equity Ownership. Tzeng:Genentech, Inc.: Employment. Shah:Genentech: Employment. Chang:Genentech, Inc.: Employment; Genentech/Roche: Equity Ownership. Niggli:F. Hoffmann-La Roche Ltd: Employment. Dhalluin:F. Hoffmann-La Roche Ltd: Employment. Mahlangu:Sanofi: Research Funding; Pfizer: Research Funding; Novartis: Research Funding; Biomarin: Research Funding; Spark: Consultancy, Honoraria, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Honoraria, Research Funding, Speakers Bureau; Catalyst Biosciences: Consultancy, Honoraria, Research Funding, Speakers Bureau; CSL Behring: Consultancy, Honoraria, Research Funding, Speakers Bureau; Baxalta: Consultancy, Honoraria, Research Funding, Speakers Bureau; Unique: Research Funding.

Efficacy and Safety of Secondary Prophylactic Versus On-Demand Sucrose-Formulated Recombinant Factor VIII Treatment in Adults with Severe Hemophilia A: Results from a 13-Month Crossover Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 516-516 ◽  
Author(s):  
Peter Collins ◽  
Albert Faradji ◽  
Massimo Morfini ◽  
Monika Maas Enriquez ◽  
Eduard Gorina ◽  
...  
Keyword(s):  
Health Economics ◽  
Factor Viii ◽  
Crossover Study ◽  
Hemophilia A ◽  
Recombinant Factor Viii ◽  
Severe Hemophilia ◽  
Joint Function ◽  
On Demand ◽  
History Of ◽  
Male Patients

Abstract Many of the physical, psychosocial, and financial difficulties associated with severe hemophilia can be attributed to the effects of recurrent joint bleeds and chronic arthropathy. Regimens for clotting factor replacement treatment for hemophilia include prophylactic and on-demand therapy. A study in pediatric male patients with severe hemophilia A showed that prophylactic treatment with sucrose-formulated recombinant factor VIII (rFVIII-FS) resulted in prevention of joint damage and a decrease in the frequency of joint and other bleeds compared with on-demand therapy (Manco-Johnson MJ, et al. N Engl J Med.2007;357:535). A clinical trial was conducted in adult patients with severe hemophilia A and history of frequent bleeding to evaluate the effect of secondary rFVIII-FS prophylaxis on the number of joint bleeds after switching from on-demand rFVIII-FS therapy. Secondary study objectives were to compare these treatment strategies with regard to joint function, number of all bleeds, health-related quality of life, health economics, and safety. Male patients who were aged 30–45 years, had a negative inhibitor status, had a history of FVIII treatment (&gt;100 exposure days), and were using on-demand FVIII treatment before the study were eligible to participate in this prospective 13-month crossover study. During the first 6 months, all patients received on-demand rFVIII-FS treatment. Patients were then switched to prophylactic rFVIII-FS treatment (20–40 IU/kg 3 times per wk at a stable dose as determined by investigators based on the patient’s bleeding history) for the remaining 7 months, with the first month constituting a washout/stabilization run-in period. Patients were monitored throughout the 13 months for bleeds and health-economics parameters and were evaluated by the Gilbert score (joint function) and the Haemo-QoL questionnaire at baseline and at the end of the on-demand (at 6 mo) and prophylactic (at 13 mo) treatment periods. A total of 20 patients from 9 international sites participated in the study. Patients received a mean dose of 31 IU/kg/wk during the on-demand period, which increased to 86 IU/kg/wk during the prophylaxis period. Although 16/20 patients already had 1 to 4 target joints, mean (±SD) numbers of joint and total bleeds per patient significantly decreased during the prophylaxis period (1.5±2.1 and 1.9±3.3, respectively) compared with the on-demand period (18.5±11.6 and 23.7±13.3; P&lt;0.001 for both). Mean (±SD) total Gilbert scores indicated better joint function at the end of prophylaxis (19.8±11.7) vs on-demand (25.3±11.7; P&lt;0.001) treatment. During this short observation period, there was no statistically significant difference between treatments in the pharmacoeconomic variables assessed (days off work, general practitioner visits, and hospitalization days) or in the mean total Haemo-QoL score, although patients reported significantly fewer restrictions at work or school by the end of the prophylaxis period compared with the end of the on-demand period (P=0.016). There was a trend toward improved patient activity levels with prophylaxis. Similar numbers of patients reported adverse events (AEs) during on-demand (n=9, 45.0%) and prophylactic (n=10, 52.6%) treatment; AEs occurring in 2 patients (dysgeusia and headache) were considered treatment related. Serious AEs were reported by 1 patient during each treatment; neither serious AE was related to treatment. No de novo inhibitor development was observed during either treatment. In summary, prophylaxis with rFVIII-FS was well tolerated and reduced the frequency of joint and other bleeds compared with on-demand treatment in previously treated adults with severe hemophilia A and target joints.

A Post-Marketing Surveillance Study of the Safety and Efficiacy of Refacto® (Moroctocog Alfa, B-Domain Deleted Recombinant Factor VIII) (St. Louis-Derived Active Substance in the Treatment and Prevension of Bleeding Episodes in Hemophilia a Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4023-4023
Author(s):  
Jay M. Feingold ◽  
Mark P. Smith ◽  
Richard Littlewood ◽  
Paul Giangrande ◽  
Keyword(s):  
Factor Viii ◽  
Active Substance ◽  
Hemophilia A ◽  
High Titre ◽  
Surveillance Study ◽  
Point Scale ◽  
On Demand ◽  
Post Marketing Surveillance ◽  
Post Marketing ◽  
Bleeding Episodes

Abstract This was an open-label, multicenter, post-marketing surveillance study conducted in Belgium, France, Germany, Italy, Netherlands, New Zealand, Switzerland, and UK. The objectives were to assess the safety and clinical efficacy of ReFacto St Louis-derived active substance (STL) in the treatment and prevention of bleeding episodes in patients with hemophilia A in the usual care setting. 60 patients with moderate to severe hemophilia A (FVIII:C <5%) with no history of FVIII inhibitor were enrolled (58 were previously treated patients and 2 were previously untreated patients). Data on infusions, concomitant medications, adverse events, and inhibitor development were collected from patients at regular intervals. Efficacy for prophylaxis was assessed by the investigator approximately every 3 months until 50 exposure days, 6 months or study termination using the number of breakthrough bleeding episodes and the 3-point scale (excellent, effective, and inadequate). The efficacy of each on-demand treatment administered was assessed using the 4-point scale (excellent, good, moderate, and no response). The investigator and surgeon assessed efficacy of surgical prophylaxis jointly after each surgery using the 4-point scale (excellent, good, moderate, and no response). Factor VIII inhibitor (using local laboratory Bethesda assay) was evaluated at screening, after 10 EDs, after 30 EDs, and at the end of treatment. The investigator determined all dosing and treatment regimens. In the prophylaxis treatment group, no particular prophylaxis regimen was enforced. A total of 32 patients aged 0–66 years initially received prophylaxis treatment: 10 (31%) patients reported no breakthrough bleeds. A median of 6.25 bleeds per year occurred in all prophylaxis patients. Twenty-nine assessments of the prophylactic treatment final outcome were made: 93% of these assessments were excellent or effective. A total of 28 patients aged 1–71 years initially received on-demand treatment with ReFacto STL. 95.2% of bleeds were resolved with 1 or 2 infusions. The assessment of treatment response was excellent or good in 98% of cases. Seven patients underwent 7 surgical procedures, haemostasis was achieved all cases and ReFacto STL was rated as providing an excellent or good response as the final outcome in each case. As this was a post-marketing study, safety evaluation was focused on collection of serious AEs and product-related non-serious AEs. One PTP (1/58, 1.7%) developed a high titre inhibitor and 1/58 (1.7%) developed a low titre transient inhibitor. One PUP developed a low titre transient inhibitor (0.4 BU). SAEs included 1 fatal intracranial hemorrhage (considered unrelated to ReFacto), 5 preplanned surgeries, 1 episode of gastroenteritis, and 1 hemorrhage. There were no allergic events. Three patients were withdrawn from treatment for safety reasons (1 patient due to death, 1 PTP due to high titre inhibitor and 1 PTP due to low titre transient inhibitor). The nature and incidence of non-serious AEs did not raise new safety concerns. The majority of AEs were mild or moderate in severity.

Prophylactic Use of rFVIIa in a Young Hemophilia A Patient with Factor VIII Inhibitor.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4068-4068
Author(s):  
Annie Borel-Derlon ◽  
Mounia Slaoui ◽  
Philippe Gautier ◽  
Patricia Guillon
Keyword(s):  
Quality Of Life ◽  
Factor Viii ◽  
Immune Tolerance ◽  
Hemophilia A ◽  
Factor Viia ◽  
High Dose ◽  
Factor Viii Inhibitor ◽  
On Demand ◽  
Viii Inhibitor

Abstract The prevention of bleeding by prophylaxis regimen particularly for joint rehabilitation, could be considered a more effective treatment for hemophilia patients. In hemophiliacs with factor VIII inhibitor (F VIII inh) prophylaxis is not generally proposed because the bypassing agents for these patients may be less effective than F VIII concentrates. We report the regimen and results of a 6 months rFVIIa (Recombinant factor VIIa) prophylaxis, in a young hemophilia A patient (4 years old), with F VIII inh and immune tolerance induction (ITI) treatment and compared, with rFVIIa, the on demand treatment results for the 6 months prior to prophylaxis. After 2 years of a high dose regimen ITI, the FVIII inh titer was less than 50 BU and the immune tolerance treatment remains on going. Due to the development of a right knee target joint the rFVIIa prophylaxis was decided as an active rehabilitation approach to prevent the development of chronic arthropathy as well as to improve the quality of life of the child. During the 6 months period, prior to the initiation of rFVIIa prophylaxis 22 bleeds occurred i.e., 9 right knee hemarthrosis and 13 other joint bleedings and hematoma including elbow, wrist, ankle, foot, arm and chest. These bleeds were all treated with rFVIIa with a dose ranging from 100 to 200 μg/kg depending on the severity of the episodes and the duration of treatment ranged from 1 to 8 days. After 6 recurrent right knee hemarthrosis, a lavage of the joint was performed and prophylaxis with rFVIIa was subsequently initiated. A 120 μg/kg rFVIIa injection was performed 3 times a week concomitantly with the ITI treatment infusion and just before the physiotherapy course. During the 6 months of prophylaxis regimen we observed 9 bleeds with 3 major post traumatic bleedings which were treated by one 200 μg/kg/day rFVIIa injection which was resolved in one to three days. This prophylaxis treatment was effective for the arthropathy evolution and permitted the patient to return to school on a regular basis compared to the previous year. The total dose of on demand rFVIIa treatment used before prophylaxis was 458 mg/6 months. This amount decreased by 25% during the six months of prophylaxis with rFVIIa to reach 343 mg. The results of this significant observation led us to conclude that rFVIIa could be effectively used as prophylactic treatment in patients with FVIII inh and administered safely via a portacath device even in cases of high doses, as demonstrated in this young patient. This prevention approach resulted in a decrease of bleeding episodes, injections, and a significant improvement in the quality of life.

scholarly journals Clinicopathological parameters influencing inhibitor development in patients with hemophilia A receiving on-demand therapy

2018 ◽  
Vol 9 (8) ◽  
pp. 213-226 ◽  
Author(s):  
Sanya Arshad ◽  
Anshima Singh ◽  
Namrata Punit Awasthi ◽  
Swati Kumari ◽  
Nuzhat Husain
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Age At Onset ◽  
North India ◽  
Clinicopathological Parameters ◽  
Factor Viii Inhibitor ◽  
Inhibitor Development ◽  
On Demand ◽  
Group B ◽  
Subtype A

Background: Development of inhibitors to transfused factor VIII in patients with hemophilia A continues to be a challenge for professionals involved in hemophilia care. The majority of patients in India receive ‘on-demand’ rather than prophylactic therapy. The present study was done to assess the prevalence of factor VIII inhibitors in patients with hemophilia A (PWHA) receiving ‘on-demand’ therapy in a North Indian population and to study the clinicopathological parameters influencing the development of inhibitors. Methods: The study group comprised of 300 PWHA. Detailed clinical parameters, treatment history, bleeding profile including family history were recorded. Diagnosis of hemophilia A was confirmed by relevant coagulation tests. Inhibitors were screened using mixing based studies followed by quantification by Bethesda assay and Nijmegen modified Bethesda assay. Samples were collected from five cities in North India where a free supply of factor VIII was available and effectively used in three of these cities. Results: In the 300 PWHA, disease phenotype was severe in 219 (73%), moderate in 62 (20.67%) and mild in 19 (6.34%), based on the factor VIII bioassay. Inhibitor prevalence was 9.6% ( n = 29) and seen only in the severe phenotype. Inhibitor titers ranged from 0.8 to 108.8 BU/ml. A total of 12 PWHA had low and 17 had high titers. Correlation of various clinicopathological parameters in inhibitor-positive versus negative PWHA showed significant correlation with age at onset of disease, severity of disease, age at first exposure to treatment, annual factor intake (IU/kg/year), intense treatment episodes and bleeding manifestations like central nervous system bleed and hematuria. The total study sample had blood group B in 33.34% PWHA, followed by O (27.34%), A (24.34%) and AB (15%), however, in inhibitor-positive samples, significant inhibitor formation was associated with the ABO subtype A (19/29, 65.51%). Conclusions: Factor VIII inhibitor prevalence in PWHA receiving ‘on-demand’ therapy was 9.6%. Clinicopathological correlates of inhibitor development in such PWHA have been analyzed in this novel study.

scholarly journals Patterns of Prior Treatment and Bleeds Among Patients with Severe Hemophilia a: Impact on Frequency of Dosing with Bay 81-8973 in the Leopold I Trial

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1103-1103 ◽  
Author(s):  
Nikki Church ◽  
Rajeev Ayyagari ◽  
Jennifer Pocoski ◽  
Gautam Sajeev ◽  
Sneha S Kelkar ◽  
...  
Keyword(s):  
Factor Viii ◽  
Research Funding ◽  
Hemophilia A ◽  
Prior Treatment ◽  
Recombinant Factor Viii ◽  
Average Dose ◽  
Severe Hemophilia ◽  
On Demand ◽  
Dosing Frequency ◽  
The Impact

Abstract Background: BAY 81-8973 is an investigational recombinant factor VIII (FVIII) product with recommended prophylactic dosing of 20-40 IU/kg at least 2x or 3x weekly for patients with severe hemophilia A. The frequency of dosing with FVIII is among several decisions made by treating physicians and potentially affects effectiveness and cost. The impact of prior bleeds or prior FVIII treatment on the choice of BAY 81-8973 dosing frequency has not been studied previously and may help clarify the association of dosing frequency with effectiveness. This study examines the association between prior treatment patterns and bleeds with dose frequency assignment in patients from the LEOPOLD I (LEO I) trial. Methods: Data from part B of the phase II/III randomized, open-label crossover LEO 1 trial were analyzed. The sample consisted of patients who received prophylactic treatment with BAY 81-8973 during the 12-month LEO I study period. At study start, patients were assigned to a dose and a frequency of either 2x/week or 3x/week at the investigator's discretion; once assigned, the dose and frequency were unchanged through the study period. This analysis compared physician-recorded pre-enrollment FVIII treatment frequencies and bleeds during the last 12 months prior to enrollment between the 2x/week and 3x/week groups. Wilcoxon rank sum tests were used to compare average dose per FVIII injection and number of bleeds, and chi-square tests were used for mode of treatment (on-demand or prophylaxis) and FVIII treatment frequencies. Results: Among 62 patients in the trial, mean age was 31.5 years and 89% were Caucasians. FVIII prophylaxis frequencies ranged from daily to 1x/week prior to enrollment. 11 patients in the 2x/week group had received pre-enrollment FVIII prophylaxis at a frequency of 2x/week (Table 1). 28 patients in the 3x/week group had received FVIII injections at a frequency of 3x/week prior to enrollment. Some of these patients in each group had also received pre-enrollment FVIII prophylaxis at other frequencies. Average FVIII doses per injection in IU/kg were higher in the 2x/week group for prior on-demand and prophylactic therapy, but these differences were not statistically significant. The majority of patients in the 2x/week group (56%) and the 3x/week group (59%) had received Bayer's sucrose-formulated recombinant factor VIII prior to enrollment. Regardless of prior mode of treatment, the average number of bleeds in the last 12 months before enrollment was higher in the 3x/week group (13.4 bleeds) than in the 2x/week group (7.1 bleeds). Conclusions: Investigator selection of 2x/week or 3x/week dosing frequency was correlated with the regimen patients were on prior to enrollment. Patients receiving FVIII 3x/week had, overall, more frequent bleeding episodes than patients in the 2x/week group in the year prior to enrollment, suggesting that a phenotypic approach can well be used for dosing with Bay 81-8973. Disclosures Church: Bayer Healthcare Pharmaceuticals: Employment. Ayyagari:Bayer Healthcare Pharmaceuticals: Consultancy, Research Funding. Pocoski:Bayer Healthcare Pharmaceuticals: Employment. Sajeev:Bayer Healthcare Pharmaceuticals: Consultancy, Research Funding. Kelkar:Bayer Healthcare Pharmaceuticals: Consultancy, Research Funding. Du:Bayer Healthcare Pharmaceuticals: Consultancy, Research Funding. Mass-Enriquez:Bayer Healthcare Pharmaceuticals: Employment. Xie:Bayer Healthcare Pharmaceuticals: Consultancy, Research Funding.

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.

Sign in / Sign up

Export Citation Format

Share Document