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INTRODUCTION: Factor IX replacement therapy is used for treatment and prophylaxis of bleeding in haemophilia B. rIX-FP is an extended half-life albumin-fusion protein, which, in clinical studies, has demonstrated prolonged dosing intervals up to 21 days for routine prophylaxis, providing therapeutic benefit. AIMS: To describe dosing frequency and consumption (primary endpoint), efficacy and safety of rIX-FP treatment during routine clinical practice in Italy. METHODS: Patients with moderate/severe haemophilia B on prophylaxis with rIX-FP for ≥6 months, were enrolled in this observational study from October 2017 to February 2019 and followed-up for 2 years. Descriptive analysis included prospective and retrospective data (12 months prior to switching to rIX-FP). RESULTS: Data were collected from 59 male patients (median age 30.1 years) enrolled by 23 Italian centres. Of them, 50 were on prophylaxis during the entire observation period and completed the study. The infusion frequency changed from 2-3 times/week in 86.0% of patients with previous treatment, to less than once a week in 84.0% of patients treated with rIX-FP at the 2nd-year follow-up. The annual number of infusions decreased by about 70%, whereas the mean FIX activity trough level increased from 3.8% to 14.4% (mean > 10% in all the infusion regimens). Median Annualised Bleeding Rate of .0 was achieved across all prophylaxis regimens. Subjects with zero bleedings increased from 66.0% to 78.0% with rIX-FP. CONCLUSION: Treatment with rIX-FP reduced infusion frequency, while providing higher FIX trough levels with substantial benefit in terms of annualised bleeding rate and a good safety profile.
Asunto(s)
Factor IX , Hemofilia B , Adulto , Humanos , Masculino , Albúminas , Factor IX/uso terapéutico , Hemofilia B/tratamiento farmacológico , Hemorragia/prevención & control , Hemorragia/tratamiento farmacológico , Italia , Estudios Prospectivos , Proteínas Recombinantes de Fusión/uso terapéutico , Estudios RetrospectivosAsunto(s)
Hemofilia A , Procedimientos Ortopédicos , Humanos , Hemofilia A/complicaciones , Hemofilia A/tratamiento farmacológico , Procedimientos Ortopédicos/efectos adversos , Adulto , Masculino , Persona de Mediana Edad , Tromboembolia Venosa/prevención & control , Tromboembolia Venosa/etiología , Anticoagulantes/uso terapéutico , Adulto JovenRESUMEN
Emicizumab is a humanized recombinant bispecific antibody, bridging together activated factor IX (FIXa) and factor X (FX), thus mimicking the activity of FVIII in vivo. Emicizumab is designed for long-term prophylaxis in patients with severe hemophilia A with and without inhibitors. This approach provides constant protection, with significant reduction in bleeding rate and improved quality of life. However, protection provided by emicizumab is not absolute, and clotting factor concentrates (FVIII, rFVIIa, aPCC) may be necessary for post-traumatic bleeding or surgery, with a potential thrombotic risk or difficulty in preventing bleeding. Real world evidence is still scanty, especially for managing major surgery. In this study, 75 surgeries were managed in 28 patients (27 major procedures in 15 patients and 48 minor procedures in 20 patients. In 17 patients without inhibitors, 30 minor surgeries were carried out by using FVIII in 5, with only a bleeding event, which was successfully treated with FVIII concentrate. Six major surgeries were uneventfully performed with FVIII concentrate. Eleven PWHA and high-titer inhibitors underwent 39 surgical procedures (18 minor and 21 major surgeries). Minor surgeries were mostly performed without prophylaxis with rFVIIa, with only a single bleeding complication. All 21 major surgeries were covered with a homogeneous protocol using rFVIIa. In four instances, bleeding complications occurred, treated with rFVIIa. Of them, a single patient only failed to respond and died because of an uncontrollable bleeding from a large ruptured retroperitoneal pseudotumor. Surgery in patients with emicizumab can be safely carried out with the use of appropriate replacement therapy protocols.
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Background: Intracranial hemorrhage (ICH) is a highly serious event in patients with haemophilia (PWH) which leads to disability and in some cases to death. ICH occurs among all ages but is particularly frequent in newborns. Aim: The primary aim was to assess the incidence and mortality due to ICH in an Italian population of PWH. Secondary aims were to evaluate the risk factors for ICH, the role of prophylaxis, and the clinical management of patients presenting ICH. Methods: A retrospective-prospective registry was established in the network of the Italian Association of Haemophilia Centers to collect all ICHs in PWH from 2009 to 2019 reporting clinical features, treatments, and outcomes. Results: Forty-six ICHs were collected from 13 Centers. The ICHs occurred in 15 children (10 < 2 years), and in 31 adults, 45.2% of them with mild hemophilia. Overall, 60.9% patients had severe haemophilia (15/15 children). Overall ICH incidence (×1000 person/year) was 0.360 (0.270−0.480 95% CI), higher in children <2 years, 1.995 (1.110−3.442 95% CI). Only 7/46 patients, all with severe haemophilia, had received a prophylactic regimen before the ICH, none with mild. Inhibitors were present in 10.9% of patients. In adult PWHs 17/31 suffered from hypertension; 85.7% of the mild subjects and 29.4% of the moderate/severe ones (p < 0.05). ICH was spontaneous in the 69.6% with lower rate in children (46.7%). Surgery was required in 21/46 patients for cerebral hematoma evacuation. Treatment with coagulation factor concentrates for at least three weeks was needed in 76.7% of cases. ICH was fatal in 30.4% of the cases. Of the survivors, 50.0% became permanently disabled. Only one-third of adult patients received long term prophylaxis after the acute treatment. Conclusion: The results from our Registry confirm the still high incidence of ICH in infants <2 years and in adults, particularly in mild PWHs presenting hypertension and its unfavorable outcomes. The majority of PWHs were treated on-demand before ICH occurred, suggesting the important role of prophylaxis in preventing such life-threatening bleeding.
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Treating hemophilia A or B patients with inhibitors is particularly challenging, as they do not respond to replacement therapy with factor VIII or factor IX concentrates. A room temperature-stable formulation of recombinant activated factor VII (rFVIIa; NovoSeven ® ), which provides improved convenience and treatment access to patients compared with the earlier formulation of rFVIIa, was shown to be safe and effective in a post-authorization, multinational, observational study (Study Monitoring Antibodies against Room Temperature-stable factor 7 [SMART-7™]). In post hoc, subgroup analyses of SMART-7™ data, the hemostatic response following rFVIIa monotherapy in patients with hemophilia A or B with inhibitors by time to first treatment and in different age cohorts was assessed. A total of 482/618 bleeding episodes treated with rFVIIa monotherapy and with (1) valid efficacy assessment, (2) no missing time for bleed start, (3) no missing time for any dose administration, and (4) valid time to first treatment were included in the analyses. Data on the type and location of bleeding episodes treated with rFVIIa monotherapy were also collected. The majority of bleeding episodes treated with rFVIIa monotherapy were treated within 1 hour after bleeding onset (318/482 [66%]) and, among them, 96.5% (307/318) were effectively treated (i.e., bleeding stopped). Hemostatic efficacy remained high for bleeding episodes treated >1 to ≤4 hours after the onset, with 94/101 (93.1%) treated effectively. Cause and location of bleeding varied across the different age groups assessed. Real-world evidence from post hoc, subgroup analyses of SMART-7™ data confirmed that patients were able to treat themselves quickly and that early treatment with rFVIIa was associated with high efficacy.