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Introduction: Women or girls with haemophilia (WGH) represent a group of female symptomatic carriers who experience bleeding events more frequently than non-carriers. Bleeding events include spontaneous/traumatic bleeds and prolonged bleeding related to surgery, menstruation and pregnancy. Challenges for the treatment of WGH include lack of screening, diagnosis and treatment guidelines., Aim: Evaluate clinical characteristics, haemostasis management and clinical outcomes regarding menstruation, childbirth, dental procedures, surgeries and other bleeding events in WGH., Methods: A retrospective, non-interventional review of medical records from WGH among three haemophilia treatment centres (HTCs) was conducted in the United States (2012-2018). Patients with ≥2 visits to the HTC and who had undergone intervention for haemostasis management with the outcome documented were included. Descriptive statistics were used., Results: Of 47 women and girls included in the chart review (37 with factor VIII deficiency, 10 with factor IX deficiency), median age at diagnosis was 22.6 years. Approximately 79% (n = 37) were diagnosed with mild haemophilia. Events of interest were primarily managed by factor concentrates or antifibrinolytics. Most treatment approaches were successful across clinical scenarios, except for heavy menstrual bleeding being insufficiently controlled in 8 (57%) of the 14 patients who experienced it., Conclusions: Bleeding events in WGH, such as excessive and prolonged bleeding during menstruation, demonstrate a unique burden and require specific medical intervention. These results highlight the importance of assessing the need for haemostasis management in WGH and may contribute to future prospective study designs., (© 2020 John Wiley & Sons Ltd.)

Introduction: In clinical trials, recombinant factor IX fusion protein (rFIXFc) has demonstrated safety, efficacy and prolonged activity with extended dosing intervals for treatment of haemophilia B., Aim: To assess the real-world clinical utility of rFIXFc in a variable patient population and routine clinical practice., Methods: A multicentre, retrospective chart review was conducted of patients with haemophilia B who had received rFIXFc prophylaxis or on-demand treatment for ≥6 months across six sites in the United States., Results: Sixty-four eligible patients were identified who had a median (range) duration on rFIXFc of 2.7 (0.5-5.0) years. Of 32 patients on rFIXFc prophylaxis who switched from prophylaxis with another factor treatment (ie pre-rFIXFc) and had a known pre-rFIXFc dosing interval, the initial dosing interval was lengthened for 26 (81%) patients and maintained for the remaining 6 (19%) patients. Most (n = 48 [91%]) patients who received rFIXFc prophylaxis from the beginning to the end of the chart review period (n = 53) maintained or lengthened the dosing interval from first through last dose of rFIXFc. For patients receiving rFIXFc prophylaxis, there was an approximate 50% reduction in weekly factor consumption compared with pre-rFIXFc prophylaxis. Overall annualized bleed rates, annualized spontaneous bleed rates and annualized joint bleed rates decreased after switching to rFIXFc prophylaxis (n = 24 with bleed data). Compliance to recommended treatment improved or remained stable in most patients with available data (30/31)., Conclusion: Recombinant factor IX fusion protein prophylaxis improved bleed control, reduced overall consumption, reduced frequency of infusion and improved compliance for patients with haemophilia B in a real-world setting., (© 2020 The Authors. Haemophilia published by John Wiley & Sons Ltd.)

Cold agglutinin disease (CAD) is a rare, complement-mediated autoimmune hemolytic anemia. Patients with CAD in the United States and Europe have an increased incidence of thromboembolism (TE), but comparable information for patients in other regions is lacking. Thus, we examined TE risk for patients with CAD in Japan. Patients with CAD (at least three claims with a CAD diagnosis; Japanese Disease Code 2830009) and non-CAD controls were retrospectively identified (2008-2017) from a large hospital-based administrative claims dataset in Japan. Cohorts were compared using conditional logistic regression. We identified 344 patients with CAD (53.2% female; mean age: 66.8 years) and 3440 matched controls. Patients with CAD had higher TE rates than controls (34.9% vs. 17.9%; P < 0.0001). Both arterial and venous TEs were increased in the CAD group when compared with the control group (25.0% vs. 4.6% and 8.4% vs. 4.0%, respectively; both P < 0.0001). Most arterial TEs in the CAD cohort (87.2%) were myocardial infarctions. The overall odds ratio for TE development in CAD was 2.81 (95% confidence interval 2.18-3.61). CAD in Japan is characterized by an increased risk of TE. The rate of arterial TEs was particularly high in this patient population.

Objective: Late-onset Pompe disease is a progressive, debilitating, and often fatal neuromuscular disorder resulting from the deficiency of a lysosomal enzyme, acid α-glucosidase. This extension study was conducted to determine the durability of the efficacy and safety of alglucosidase alfa observed over a period of 78 weeks in the Late-Onset Treatment Study (LOTS)., Methods: Patients who completed the LOTS study were eligible for this open-label extension study and received alglucosidase alfa 20mg/kg biweekly for an additional 26 weeks. The primary efficacy assessments were the distance walked during a 6-minute walk test and the percentage of predicted forced vital capacity in the upright position. Data are reported as change from patient's original LOTS baseline for each measure., Results: The benefit of alglucosidase alfa treatment observed in LOTS at Week 78 was, in general, maintained at Week 104. The mean increase in distance walked measured 28.2 ± 66.5m from LOTS baseline to Week 78 and 21.3 ± 78.0m from LOTS baseline to Week 104. The mean change from baseline in percentage of predicted forced vital capacity was 1.3% ± 5.7% from LOTS baseline to Week 78 and 0.8% ± 6.7% from LOTS baseline to Week 104. Treatment-related adverse events were mainly infusion-associated reactions observed in 35% of patients. No deaths or anaphylactic reactions were observed during the extension study., Conclusions: The LOTS Extension study showed that patients treated with alglucosidase alfa for up to 104 weeks maintained the improved walking distance and stabilization in pulmonary function observed in the first 78 weeks of alglucosidase alfa therapy., (Copyright © 2012 Elsevier Inc. All rights reserved.)

In a previous 52-wk trial, treatment with alglucosidase alpha markedly improved cardiomyopathy, ventilatory function, and overall survival among 18 children <7 mo old with infantile-onset Pompe disease. Sixteen of the 18 patients enrolled in an extension study, where they continued to receive alglucosidase alpha at either 20 mg/kg biweekly (n = 8) or 40 mg/kg biweekly (n = 8), for up to a total of 3 y. These children continued to exhibit the benefits of alglucosidase alpha at the age of 36 mo. Cox regression analyses showed that over the entire study period, alglucosidase alpha treatment reduced the risk of death by 95%, reduced the risk of invasive ventilation or death by 91%, and reduced the risk of any type of ventilation or death by 87%, compared with an untreated historical control group. Cardiomyopathy continued to improve and 11 patients learned and sustained substantial motor skills. No significant differences in either safety or efficacy parameters were observed between the 20 and 40 mg/kg biweekly doses. Overall, long-term alglucosidase alpha treatment markedly extended survival as well as ventilation-free survival and improved cardiomyopathy.