Pharmacokinetic study of Kovaltry in thirty‐five pediatric patients aged <12 years with severe hemophilia A

Haemophilia ◽  
2021 ◽  
Author(s):  
Kun Huang ◽  
Yingzi Zhen ◽  
Gang Li ◽  
Xinyi Wu ◽  
Runhui Wu ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Pediatric Patients ◽  
Hemophilia A ◽  
Severe Hemophilia

Target Joint Bleeding in Pediatric Patients with Hemophilia Α Receiving Twice Weekly Prophylaxis with a Pegylated Full-Length Recombinant Factor VIII with Extended Half-Life

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3778-3778
Author(s):  
Amy L. Dunn ◽  
Alexis A. Thompson ◽  
Werner Engl ◽  
Marlies Sharkhawy ◽  
Brigitt E. Abbuehl
Keyword(s):  
Factor Viii ◽  
Board Of Directors ◽  
Half Life ◽  
Research Funding ◽  
Pediatric Patients ◽  
Hemophilia A ◽  
Point Estimate ◽  
Severe Hemophilia ◽  
Advisory Committees ◽  
The Mean

Abstract Introduction: Patients with hemophilia A are at risk for acute bleeding which may affect muscles and other soft tissues but characteristically involves joints. Prophylaxis with factor VIII (FVIII) is the optimal treatment to prevent bleeding into joints and, when begun at a young age, may prevent arthropathy. BAX 8551, a polyethylene glycol (peg)ylated, full-length, recombinant FVIII built on ADVATE2, demonstrated extended half-life, efficacy, and safety for prophylaxis and treatment of bleeding in patients with severe hemophilia A. Methods: A phase 3, prospective, uncontrolled, multicenter study was performed in pediatric patients with severe hemophilia A without history of inhibitors. To be eligible, patients aged <6 years had to have ≥50, those aged 6 to <12 years ≥150 previous exposure days (EDs) to FVIII. Patients received twice weekly infusions of 50 ±10 IU/kg of BAX 855 over a period of 6 months or ≥50 EDs. The prevalence of target joints, defined as a single joint with ≥3 spontaneous bleeding episodes in any consecutive 6-month period, was assessed at baseline. Annualized rates of target joint bleeds and the course of target joints were evaluated by age (<6 and 6 to <12 years). The study was performed in accordance with the principles of the Declaration of Helsinki of the World Medical Association. Results:Sixty-six patients were treated with a mean (SD) BAX 855 dose of 51.1 (5.5) IU/kg at a mean (SD) frequency of 1.8 (0.2) infusions/week. Fourteen of 66 patients (21.2%), 3/32 (9.4%) in the younger and 11/34 (32.4%) in the older cohort, had a total of 23 target joints at screening. The number of target joint bleeds decreased during a mean (SD) of 48.5 (7.7; median: 49.0) prophylactic EDs/patient. Five of 66 (7.6%) patients had at least 1 target joint bleed, 1/32 (3.1%) in the younger and 4/34 (11.8%) in the older cohort. The point estimate for the mean (95% CI) annualized rate of target joint bleeds was 0 (0 - infinity; median: 0) compared to an annualized rate of all joint bleeds of 1.1 (0.6 - 1.9; median: 0) and an annualized rate of all bleeds of 3.0 (2.2 - 4.2; median: 2.0) (Table 1). The point estimate for the mean (95% CI) annualized bleeding rate (ABR) in 52 patients without target joints was 2.9 (2.0 - 4.2; median: 2.0) and was similar in 14 patients with target joints at screening at 3.5 (1.9 - 6.6; median: 2.1). In the younger cohort, the ABR was lower in patients with than those without target joints. However, the number of patients <6 years with target joints (N = 3) was too small to draw any conclusions (Table 1). During BAX 855 prophylaxis, no new target joints developed in any patient. Ten of 14 patients had at least 1 target joint revert to a non-target joint. In 8 of these 10 patients, 4 with 1 and 4 with 2 target joints, all target joints resolved. Conclusions:These results suggest that twice weekly infusion of BAX 855 is effective in the prevention of bleeding into target joints and may revert target to non-target joints in pediatric patients with severe hemophilia A. 1BAX 855 (Baxalta US Inc., now part of Shire) is licensed in the US and Japan under the trade name ADYNOVATE. 2ADVATE is a trade mark of Baxalta US Inc., now part of Shire. Disclosures Dunn: NovoNordisk: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kedrion: Research Funding; Pfizer: Research Funding; CSL Behring: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biogen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Baxalta (now part of Shire): Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Research Funding. Thompson:Eli Lily: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; bluebird bio: Consultancy, Research Funding; ApoPharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Mast: Research Funding; Amgen: Research Funding; Baxalta (now part of Shire): Research Funding. Engl:Shire: Employment, Equity Ownership. Sharkhawy:Baxalta (now part of Shire): Employment. Abbuehl:Baxalta (now part of Shire): Employment.

scholarly journals Direct comparison of two extended-half-life recombinant FVIII products: a randomized, crossover pharmacokinetic study in patients with severe hemophilia A

2019 ◽  
Vol 98 (9) ◽  
pp. 2035-2044 ◽  
Author(s):  
Anita Shah ◽  
Alexander Solms ◽  
Sara Wiegmann ◽  
Maurice Ahsman ◽  
Erik Berntorp ◽  
...  
Keyword(s):  
Pharmacokinetic Study ◽  
Half Life ◽  
Hemophilia A ◽  
Severe Hemophilia ◽  
Recombinant Fviii

scholarly journals Aggressive Neuroblastoma in a Pediatric Patient with Severe Hemophilia A

2021 ◽  
Vol 13 (1) ◽  
pp. 125-130
Author(s):  
Lidia Costa ◽  
Maria Eduarda Couto ◽  
Juliana Moutinho ◽  
Ana Maia Ferreira ◽  
Emilia Costa ◽  
...  
Keyword(s):  
Pediatric Patient ◽  
Rare Case ◽  
Pediatric Patients ◽  
Hemophilia A ◽  
Negative Impact ◽  
Severe Hemophilia ◽  
Hemorrhagic Complications ◽  
Extensive Information

Despite the extensive information regarding hemophilia’s hemorrhagic complications, the literature on cancer in hemophilia is scarce, especially in pediatric patients. Many uncertainties remain concerning diagnosis and workup. We report a rare case of two severe diseases (neuroblastoma and hemophilia A (HA)) concomitantly present in the same pediatric patient. We highlight that the diagnosis of severe HA did not have a negative impact on the patient’s oncologic course. This case also illustrates the significance of the cooperation among different specialties and hospitals when caring for the same patient.

scholarly journals Every 2 Weeks or Every 4 Weeks Subcutaneous Injection of Emicizumab in Pediatric Patients with Severe Hemophilia A without Inhibitors: A Multi-Center, Open-Label Study in Japan (HOHOEMI Study)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1186-1186 ◽  
Author(s):  
Midori Shima ◽  
Keiji Nogami ◽  
Sayaka Nagami ◽  
Seitaro Yoshida ◽  
Koichiro Yoneyama ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Interim Analysis ◽  
Research Funding ◽  
Pediatric Patients ◽  
Hemophilia A ◽  
Bispecific Antibodies ◽  
Severe Hemophilia ◽  
Advisory Committees ◽  
Favorable Safety ◽  
Cutoff Date

Abstract Introduction: Emicizumab is a novel, subcutaneously injectable, recombinant humanized bispecific monoclonal antibody which mimics the function of activated coagulation factor VIII. Due to its mechanism of action and lack of sequence homology, emicizumab is not expected to induce or be affected by anti-factor VIII (FVIII) antibodies (inhibitors). Emicizumab once-weekly dosing has been approved for hemophilia A patients with inhibitors of all ages in several countries. A clinically meaningful prophylactic effect and favorable safety of emicizumab given every 2 weeks (Q2W) and every 4 weeks (Q4W) in adult/adolescent patients has been demonstrate in HAVEN3 study (NCT02847637) and HAVEN4 study (NCT03020160). This is the first report to assess emicizumab prophylaxis in pediatric patients without inhibitors including a patient previously untreated with FVIII. Methods: The present study (JapicCTI-173710) enrolled Japanese patients aged <12 years with hemophilia A without inhibitors. Patients received a loading dose of 3 mg/kg weekly for the first 4 doses, followed by a maintenance dose of 3 mg/kg Q2W or 6 mg/kg Q4W. This interim analysis was performed after at least 6 patients in each dosing cohort had completed at least 12 weeks of treatment with emicizumab prophylaxis. Results: A total of 13 male patients were enrolled in 2 cohorts. The numbers of patients aged 0 - < 2, 2 - < 6, and 6 - < 12 years were 1, 2, and 3 in the Q2W cohort and 2, 2, and 3 in the Q4W cohort. All patients had been previously treated with FVIII prophylaxis except for 1 patient aged 4 months in the Q4W cohort who was previously untreated. As of the data cutoff date of March 14, 2018, the medians (range) of treatment duration were 21 (18.3 - 22.1) and 16 (4.3 - 16.6) weeks in the Q2W and Q4W cohorts, respectively. The interim analysis results showed a clinically meaningful effect of emicizumab prophylaxis with the Q2W and Q4W regimens. As of the data cutoff date, 3/6 patients in the Q2W cohort and 5/7 patients including 1 patient previously untreated with FVIII in the Q4W cohort experienced no treated bleeds. There were no treated spontaneous bleeds and a total of 6 treated bleeds were traumatic. Two out of them were treated joint bleeds. Model-based annualized bleeding rates for treated bleeds with FVIII products under emicizumab prophylaxis were 1.6 (95% CI, 0.60 to 4.25) and 1.0 (95% CI, 0.25 to 4.06) in the Q2W and Q4W cohorts, respectively. All 13 patients experienced at least 1 adverse event (AE) and a total of 78 AEs were reported. There were no AEs that were grade 3 or higher, serious, led to withdrawal from treatment, or resulted in dose modification or interruption. None of the AEs were considered related to emicizumab. Neither thromboembolic events, thrombotic microangiopathy, systemic hypersensitivity reactions, nor local injection site reactions were reported. The most frequent AEs were contusion in 10 (76.9%) patients, excoriation and nasopharyngitis in 4 (30.8%) patients each, and ligament sprain and influenza in 3 (23.1%) patients each. The emicizumab exposures observed in this study were within the observed variability in preceding studies. No effects of age or body weight on emicizumab exposure were evident. Conclusions: This interim analysis results suggested clinically meaningful efficacy and favorable safety of the emicizumab Q2W and Q4W regimens in patients aged <12 years with severe hemophilia A without inhibitors. This suggests that it should be appropriate to apply the same dosing regimens of emicizumab for pediatric patients without inhibitors and other patient populations of hemophilia A. The updated results of primary analysis after completing at least 24 weeks on emicizumab treatment will be presented at the meeting. Disclosures Shima: Chugai Pharmaceutical Co., Ltd: Consultancy, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: Anti-FIXa/X bispecific antibodies , Research Funding, Speakers Bureau; F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees. Nogami:Chugai Pharmaceutical Co., Ltd: Consultancy, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: Anti-FIXa/X bispecific antibodies , Research Funding, Speakers Bureau. Nagami:Chugai Pharmaceutical Co., Ltd: Employment, Equity Ownership. Yoshida:Chugai Pharmaceutical Co., Ltd: Employment. Yoneyama:Chugai Pharmaceutical Co., Ltd: Employment, Patents & Royalties: Anti-FIXa/X bispecific antibodies . Ishiguro:Chugai Pharmaceutical Co., Ltd: Research Funding, Speakers Bureau. Suzuki:Chugai Pharmaceutical Co., Ltd: Research Funding, Speakers Bureau. Taki:Chugai Pharmaceutical Co., Ltd: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Iliopsoas Hemorrhage in Pediatric Patients with Hemophilia, Experience from One Centre

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4571-4571
Author(s):  
Emine Türkkan ◽  
Didem Yalcin Atay ◽  
Suheyla Ocak ◽  
Gul Nihal Ozdemir
Keyword(s):  
Replacement Therapy ◽  
Pediatric Patients ◽  
Hemophilia A ◽  
Conflicts Of Interest ◽  
High Titer ◽  
Femoral Nerve ◽  
Bleeding Event ◽  
Neurological Symptoms ◽  
Severe Hemophilia ◽  
Psoas Muscles

Abstract Introduction: Iliopsoas hematoma is a serious, life threatening bleeding event in patients with hereditary clotting disorders and significantly associated with morbidity. It occurs most commonly in patients with severe hemophilia (Balkan et al Haemophilia 2005). In this review, we evaluated our patients with iliopsoas hematoma and compared with literature. Methods: The eleven pediatric patients with hemophilia and iliopsoas hematoma treated in a research and training hospital in Istanbul, between 2005 and 2015 were enrolled. The clinical characteristics including symptoms, signs, complications, and treatment were analyzed retrospectively. Results: We evaluated 14 episodes of iliopsoas hematoma from 11 patients (10 hemophilia A and 1 hemophilia B). All patients were male and the median age was 12 (8 -14) years old. Eight patients had one episode, three had two episodes. One patient had a high titer inhibitor against factor VIII. The hematoma was spontaneous and unilateral in all cases. The most common symptoms were hip pain and hip flexion contracture. Iliopsoas hematomas were confirmed by ultrasound, CT or MR scan. The treatment consisted of factor replacement and rehabilitation therapy. One patient needed erythrocytes transfusion. The mean duration of factor replacement therapy was 13.5 +/- 2.1 days. One severe hemophilia A patient with inhibitor treated with recombinant factor VIIa. Long term complications included paresthesia in 3 patients in the distribution of femoral nerve, quadriceps atrophy in 3 patients and permanent abnormal posture in one patient. Conclusion: The psoas muscles are located in the iliopsoas compartment posterior to the transversalis fascia, which is the posterior boundary of the retro peritoneum. Presentation of iliopsoas hematomas is often non-specific with abdominal, pelvic, back or groin pain or swelling. If they are large, iliopsoas hematomas can present with constipation, urinary frequency or fever. They can even compress the femoral nerve and cause a femoral neuropathy . A delay in treatment may result in permanent femoral nerve palsy (Mannucci N Engl J Med 2004). In this report, we present our experience and treatment modality in 14 episodes of iliopsoas hematoma in pediatric hemophilia patients. Rehabilitation treatment with factor replacement is safe and effective therapy for patients with small hematomas and little or no neurological symptoms. More aggressive recommendations have been made for patients with large hematomas and severe neurological symptoms or hemodynamic instability. An early diagnosis allows early factor replacement therapy, and decreases the risk of recurrence and morbidity. Disclosures No relevant conflicts of interest to declare.

Decreased Mortality From Intracranial Hemorrhage In Pediatric Patients With Hemophilia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 208-208
Author(s):  
Char Witmer
Keyword(s):  
Cohort Study ◽  
Mortality Rate ◽  
Intracranial Hemorrhage ◽  
Pediatric Patients ◽  
Hemophilia A ◽  
Interquartile Range ◽  
Administrative Database ◽  
Severe Hemophilia ◽  
Entire Cohort ◽  
Mortality Estimates

Introduction and Objective Intracranial hemorrhage (ICH) is one of the most significant bleeding complications in hemophilia with a reported 20% mortality rate. A recent study from the Centers for Disease Control and Prevention Universal Data Collection project demonstrated that prophylaxis in patients with severe hemophilia reduced the risk of intracranial hemorrhage but mortality remained high (19.6 %). However 95% of those ICH deaths occurred in subjects over 20 years of age. This was in contrast to prior studies that demonstrated much higher mortality rates in children. Additional studies are needed to confirm this shift in the age distribution of ICH mortality. The objective of this study was to determine the mortality rate from ICH in pediatric patients with hemophilia admitted to US tertiary care hospitals. Patients and methods This retrospective multicenter cohort study utilized data from 43 free-standing children’s hospitals that contribute data to the Pediatric Health Information System administrative database. Subjects were male, less than 21 years of age, with an International Classification of Diseases (ICD-9) diagnostic code for hemophilia A or B, with an admission between 1/1/2002-12/31/2011. ICD-9 discharge codes were used to identify admissions during which an ICH was diagnosed. Subjects were classified as having an inhibitor if they received bypassing agents (either FEIBA or recombinant factor VIIa). Summary statistics include frequencies and percentages for categorical variables and median and interquartile range for continuous variables. Odds ratios (OR) with 95% confidence intervals were calculated using multivariable logistic regression to evaluate the strength of association between mortality and the presence of ICH, an inhibitor and hemophilia type (A versus B). Result During the 10 year study period there were a total of 8,325 admissions in 3,133 individual male subjects with either hemophilia A or B. 80% (2,506) of the subjects had hemophilia A and 14.4% (451) had an inhibitor. The median number of admissions per subject was 1 (interquartile range 1-3). Overall mortality for the entire cohort was low at 0.7% (21 deaths). There were a total of 327 admissions with ICD-9 codes for ICH in 265 (8.5%) subjects. 12.8% (34) of subjects had more than 1 ICH event during the study period. The median age for ICH was 2.2 (interquartile range 0.6-7.3) years. The ICH mortality rate was 1.8% (6 deaths). This represents an 11 fold decrease from prior ICH mortality estimates of 20%. 50% (3) of subjects who died from ICH had an inhibitor. For the entire cohort, mortality was associated with the presence of ICH (5.6 OR (2.3-14)) and the presence of an inhibitor (3.1 OR (1.2-7.8)). Conclusion This retrospective cohort study utilizing an inpatient pediatric administrative database confirms that mortality from ICH in pediatric patients is significantly reduced from prior studies. In this cohort, mortality from ICH was quite low (1.8%), representing an 11 fold decrease from previous mortality estimates. Potential reasons for this reduction include the routine use of prophylaxis in pediatric patients with severe hemophilia, increased availability of factor concentrates and aggressive management of patients with hemophilia and suspected ICH. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document