Effectiveness of emicizumab in preventing bleeding events in severe and moderate hemophilia A: A single‐center experience in Bangladesh
Ontology highlight
ABSTRACT:
SUBMITTER: Tory S
PROVIDER: S-EPMC10887364 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundEmicizumab, a bispecific antibody factor VIII mimetic, is approved for prophylaxis in hemophilia, and has different risks and side effects compared to factor VIII products.ObjectiveTo better understand the early impact of emicizumab on our patients at the University of Colorado Hemophilia and Thrombosis Center (UCHTC), we evaluated adverse reactions, factor prophylaxis overlap, and bleeding rates after starting emicizumab through a quality improvement project.Patients/methodsA retrospective chart review and structured phone interview were conducted from June to September 2019 for all patients who had started emicizumab at the UCHTC. Data about emicizumab dosing, reactions, bleeding events, and bleeding treatment were collected in 68 children and adults (aged 0.55-79.8 years, on emicizumab a median 213 days; range, 51-1229 days) with hemophilia A (35.3% with past or current inhibitor).ResultsAdverse reactions were primarily skin reactions, with no anaphylactic reactions or thrombosis. Bleeding events, defined as pain or swelling treated with factor or supportive measures, demonstrated wide variability, with 25 of 68 experiencing zero bleeds and 5 of 68 experiencing >8 bleeds per year. The most prevalent bleed type was traumatic musculoskeletal bleeding. Bleeding events occurred more often in the first 10 weeks after starting emicizumab, but no time period was without bleeding events. The majority of patients were prescribed every-week or every-2-week dosing, but some had alternative dosing frequency.ConclusionsReal-world emicizumab use in our center was characterized by variations in prescribing practices and bleeding outcomes and lack of severe adverse reactions.
| S-EPMC8331949 | biostudies-literature
Project description:COVID-19 can be associated with coagulopathy (CAC, COVID-19-associated coagulopathy) with a high prothrombotic risk based on an intense inflammatory response to viral infection leading to immunothrombosis through different procoagulant pathways. Emerging evidence suggests that the use of heparin in these patients could be associated with lower mortality. Emicizumab is a bispecific humanized monoclonal antibody that bridges activated factor IX and factor X, thereby restoring the function of missing factor VIIIa in hemophilia A. The use of emicizumab has been associated with thrombotic events in patients who also received high cumulative amounts of activated prothrombin complex concentrates. Although this risk is extremely low, there is a lack of evidence on whether CAC increases the thrombotic risk in patients on emicizumab prophylaxis. We present the case of a patient with severe hemophilia A in prophylaxis treatment with emicizumab; due to the potential thrombotic risk we decided to administer low molecular weight heparin as prophylaxis treatment without any thrombotic or bleeding complications.
| S-EPMC7307111 | biostudies-literature
Project description:Background and objectiveEmicizumab is a monoclonal antibody that bridges activated coagulation factor IX and factor X to restore effective hemostasis in persons with hemophilia A. It is indicated for routine prophylaxis of bleeding episodes in persons with hemophilia A. The aim of the present study is to describe the exposure-response relationship between emicizumab concentrations and bleeding frequency, and to confirm adequate bleeding control of the investigated dosing regimens 1.5 mg/kg once weekly, 3 mg/kg every 2 weeks, and 6 mg/kg every 4 weeks.MethodsTreated bleeding events were pooled from 445 persons with hemophilia A with and without inhibitors against factor VIII, participating in six clinical studies. Emicizumab concentrations were predicted using a previously developed population pharmacokinetic model. A count model was used to quantify the exposure-response relationship. These models were used to illustrate the relationship between emicizumab concentrations and cumulative count of bleeding over 1 year (annualized bleeding rate).ResultsThe final exposure-response model, based on a generalized Poisson distribution and an inhibitory Emax relationship, adequately describes the relationship between daily emicizumab concentrations and daily bleed frequency. A significant effect of factor VIII prophylaxis among persons with hemophilia A without inhibitors was found. Annualized bleeding rate simulations show that the three emicizumab dosing regimens maintain the concentrations close to the plateau of the effect. At the average steady-state concentration across all regimens (53.5 µg/mL), the predicted mean annualized bleeding rate is 1.28, corresponding to a 94.0% reduction from baseline.ConclusionsThese results confirm that average emicizumab concentrations achieved with all three emicizumab dosing regimens provide adequate bleeding control.
| S-EPMC8249270 | biostudies-literature
Project description:Arthropathy of the hip is moderate in frequency in haemophiliac patients, but is less common than ankle, knee or elbow arthropathy. We report about our experience with total hip replacement in patients with severe bleeding disorders over a period of 30 years. Between July 1972 and 2002, 15 hips in 13 patients were replaced. The main bleeding disorders were Haemophilia A in ten patients and severe v. Willebrand disease in three patients. The mean follow-up was 132 months (range 12-363). We can demonstrate good long-term results, with only one aseptic loosening after 14 years and one septic loosening after 14 months in an HIV-positive patient. The Harris Hip Score increased from 48 points (32-66) preoperatively to 89 (76-100) postoperatively. In conclusion, total hip replacement performed in a specialised haemophiliac centre is a safe procedure, and results in pain relief and improvement of the quality of life in patients with severe bleeding disorders.
| S-EPMC2267532 | biostudies-other
Project description:BackgroundEmicizumab is a bispecific monoclonal antibody developed for routine prophylaxis of bleeding in people with hemophilia A (PwHA). This work characterizes the pharmacokinetics of emicizumab in adult and pediatric PwHA, identifies factors contributing to its between-person variabilities, compares the pharmacokinetics following different dosing regimens, and makes a descriptive assessment of the exposure-bleeding events relationship.MethodsA population pharmacokinetic model was developed, using a database of 389 PwHA from five clinical studies. Potential baseline covariate effects were assessed, including body size, age, race, presence of factor VIII inhibitors, and albumin levels. Using the population pharmacokinetic model, the estimated individual average exposures over the administration period were compared across categories of annualized bleeding rate.ResultsA linear one-compartment model with first-order absorption and elimination processes and no lag time best described the emicizumab pharmacokinetics. Body weight, albumin levels, age, and black race were statistically correlated with primary pharmacokinetic parameters, but only body weight had an important influence on exposure. Dosing regimens of 1.5 mg/kg weekly, 3 mg/kg every 2 weeks, or 6 mg/kg every 4 weeks provided similar average concentrations at steady state. A trend for lower exposure was observed in the small proportion of PwHA having an annualized bleeding rate > 4 (11.9%), suggesting that reducing exposure to lower levels may potentially increase the bleeding risk.ConclusionsEmicizumab pharmacokinetics in PwHA was described with dose-independent parameters. Body weight was an important predictor of emicizumab pharmacokinetics. All three dosing regimens are predicted to achieve similar exposure associated with clinically meaningful prevention of bleeding.
| S-EPMC7717049 | biostudies-literature
Project description:BackgroundThe D-dimer (DD) assay is an essential biological test for the diagnosis and monitoring of thrombotic conditions. DD testing is usually not performed as part of the routine laboratory management of patients with hemophilia (PWH). There is an increasing concern about the risk of thrombotic complications in PWH, which is likely related to age, cardiovascular risk factors, invasive thrombogenic procedures, over-correction of Factor VIII (FVIII) or FIX, or administration of new therapeutic agents mimicking FVIII or rebalancing coagulation.ObjectiveThis retrospective study sought to assess the basal DD levels in PWH treated prophylactically with FVIII, and to evaluate potential changes after switching to emicizumab.MethodPatients over 18 years of age treated with emicizumab within a single center over the period 2017-2022 were included in the study.ResultDD levels were measured in 40 adult PWH (37 severe/ three moderate / two with FVIII inhibitor) with a median age of 46 years (range: 19-82; Q1-Q3: 30,25-56,5), before and at least 3 months after emicizumab initiation. No significant changes were revealed, with DD median values of 257 ng/mL (range: 250-2876; Q1-Q3: 250-493,5) before and 250 ng/mL (range: 50-6205; Q1-Q3: 250-380,25) after the switch (p = 0.9).ConclusionMost adult PWH on prophylaxis using FVIII display DD levels within the normal range, which remain unchanged after switching to emicizumab. In view of these reassuring results, monitoring of DDs at the start of emicizumab treatment does not appear necessary but could be considered when combined with other bypassing agents or high dose FVIII.
| S-EPMC9732800 | biostudies-literature
Project description:Many people with hemophilia A (PwHA) undergo surgery in their lifetime, often because of complications of their disease. Emicizumab is the first bispecific monoclonal antibody prophylactic therapy for PwHA, and its efficacy and safety have been previously demonstrated; however, there is a need to build an evidence base on the management of PwHA on emicizumab undergoing surgery. Data from the HAVEN 1-4 phase 3 clinical trials were pooled to provide a summary of all minor and major surgeries in PwHA with or without factor VIII (FVIII) inhibitors who were receiving emicizumab prophylaxis. Overall, 233 surgeries were carried out during the HAVEN 1-4 trials: 215 minor surgeries (including minor dental and joint procedures, central venous access device placement or removal, and endoscopies) in 115 PwHA (64 with FVIII inhibitors) and 18 major surgeries (including arthroplasty and synovectomy) in 18 PwHA (10 with FVIII inhibitors). Perioperative hemostatic support was at the discretion of the treating physician. Overall, the median (interquartile range [IQR]) age was 33.5 (13.0-49.0) years and the median (IQR) emicizumab exposure time before surgery was 278.0 (177.0-431.0) days. Among the 215 minor surgeries, 141 (65.6%) were managed without additional prophylactic factor concentrate, and of those, 121 (85.8%) were not associated with a postoperative bleed. The majority (15 of 18 [83.3%]) of major surgeries were managed with additional prophylactic factor concentrate. Twelve (80.0%) of these 15 surgeries were associated with no intraoperative or postoperative bleeds. The data demonstrate that minor and major surgeries can be performed safely in PwHA receiving emicizumab prophylaxis. These trials are registered at www.clinicaltrials.gov as #NCT02622321, #NCT02795767, #NCT02847637, and #NCT03020160.
| S-EPMC9768240 | biostudies-literature
Project description:Acquired hemophilia is a rare bleeding disorder that predominantly affects older people with potential underlying comorbidities, including cardiovascular and thrombotic risk factors. The current standard therapies with hemostatic agents for acute bleeding and immunosuppression often require inpatient management, are not approved for routine bleeding prophylaxis, and contribute to the high mortality in this population. Emicizumab is a factor VIII (FVIII) mimetic approved for bleeding prophylaxis in congenital hemophilia A with and without FVIII inhibitors. Given subcutaneously, it may allow easier outpatient bleeding prophylaxis and reduce intensity of immunosuppression. This article summarizes the currently available data on the efficacy and safety of emicizumab in acquired hemophilia A.
| S-EPMC10727101 | biostudies-literature
Project description:ImportanceEmicizumab (EMI) is efficacious and safe for hemophilia A (HA) prophylaxis. However, its high cost poses a challenge in China.ObjectiveTo explore the possibility of using reduced-dosage EMI in Chinese HA children.MethodsWe conducted a retrospective study for HA children in our Comprehensive Care Center. Data were collected pre- and post-EMI treatment to evaluate bleeding rates. Laboratory analyses included factor VIII (FVIII)-like activity and EMI concentration measurements.ResultsThirty-four HA children receiving EMI prophylaxis for a median (range) 24.5 (2.5-47.9) months by June 2023. Of these, 25 (73.5%) were under 3 years of age, 26 (76.5%) had severe hemophilia and 12 (35.3%) were minimally treated or previously untreated patients. Thirty-one (91.2%) of the 34 patients received reduced-dosage EMI for economic reasons. EMI concentration and FVIII-like activity measured showed a strong correlation. Overall, while on EMI, their annual treated bleeding rate (ATBR) and annual bleeding rate (ABR) decreased significantly (2-0) while their zero-bleeding rate (ZBR) increased significantly (11.5%-65.4%). After 6 months of EMI, there was no significant difference in ATBR and ABR among various maintenance dosages. However, ZBR was significantly lower in dosages under 4 mg/kg (P = 0.0156). Receiver operator characteristic curves suggested the following cutoff values for zero bleeding: EMI 4-weekly maintenance dosage 3.8 mg/kg, EMI concentration 48.1 μg/mL, and FVIII-like activity 15.4 IU/dL.InterpretationWe showed EMI effectively prevented bleeding even at reduced dosages. However, the bleeding risk may be higher with EMI 4-weekly maintenance dosage <3.8 mg/kg, EMI concentration <48.1 μg/mL, and FVIII-like activity <15.4 IU/dL for zero bleeding. It is important that dosage reduction be done rationally. Dosage tailoring is possible.
| S-EPMC11664537 | biostudies-literature
Project description:Background Guidelines surrounding emicizumab prophylaxis and perioperative treatment for people with hemophilia A (PwHA) with factor (F)VIII inhibitors undergoing surgeries are limited. The phase IIIb multicenter, single-arm STASEY study evaluated safety and tolerability of emicizumab prophylaxis in PwHA aged ≥12 years with FVIII inhibitors. This analysis assesses surgeries during study conduct, associated hemophilia medications, and postoperative bleeds (treated and untreated). Methods PwHA with FVIII inhibitors received emicizumab 3.0 mg/kg/week for 4 weeks, then 1.5 mg/kg/week until 2 years. Surgeries were managed and documented by treating physicians. Bleeds and treatments were recorded by physicians and participants. Results Forty-six participants had ≥1 on-study surgery, 37 underwent 56 minor surgeries, and 13 underwent 22 major surgeries. Four participants underwent both minor and major surgeries. Of 18 (81.8%) and 4 (18.2%) major surgeries managed with/without additional hemostatic medication, 33.3 and 25.0% were associated with a treated postoperative bleed, respectively. Of 24 (42.9%) and 32 (57.1%) minor surgeries managed with/without additional hemostatic medication, 15.6 and 25.0% were associated with a treated postoperative bleed, respectively. Recombinant activated FVII was the most common medication for prophylaxis and bleed treatment. There were no thrombotic microangiopathies (TMAs). One hypertrophic clot, considered unrelated to emicizumab, occurred following tooth extraction. Conclusion In this challenging population with a high bleeding risk, major surgeries were performed in PwHA receiving emicizumab with/without additional hemostatic medication. Postoperative bleeds occurred following 59.1% of major surgeries; 53.8% were treated. No arterial/venous thrombotic events or TMAs occurred due to concomitant emicizumab and bypassing agents. Trial registration This trial is registered at ClinicalTrials.gov (NCT03191799).
| S-EPMC10786707 | biostudies-literature