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A low-dose immune tolerance induction (ITI) protocol incorporating immunosuppressive agents in haemophilia A children with high-titre factor VIII inhibitor and poor-ITI prognostic risk These were all on good-ITI risk patients with inhibitor titre <10 BU at the initiation of ITI and historical peak inhibitor titre <200 BU. Nineteen haemophilia A inhibitor children with poor-ITI risk (historical peak inhibitor titre >=100 BU and/or inhibitor titre >=40 BU at ITI initiation) (Table 1) were enrolled from September 2016 through April 2019. Various ITI regimens achieved an overall success rates of 60%-80%.2,3 According to the UK guideline,4 low-dose ITI (50 IU/kg, every-other-day) was only suggested for using in patient with low-titre inhibitors (historical peak inhibitors <5 BU). [Extracted from the article]

Abstract Background Quality of life (QoL) is increasingly recognized as an important outcome measure in clinical trials. The Canadian Hemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT) shows promise for use in China. Objective To adapt the CHO-KLAT version 2.0 for use in clinical trials in China. Methods Forward and back translations of the CHO-KLAT2.0 were completed in 2008. Between October 2009 and June 2010, a series of 3 focus groups were held with 20 boys and 31 parents in rural and urban China to elicit additional concepts, important to their QoL, for the Chinese CHO-KLAT2.0. All of the items identified by boys and parents were reviewed by a group of experts, resulting in a Chinese version of the CHO-KLAT2.0. This version underwent a detailed cognitive debriefing process between October 2010 and June 2011. Thirteen patient-parent pairs participated in this cognitive debriefing process until a stable and clearly understood Chinese version of the CHO-KLAT2.0 was obtained. Results The initial back translation of the Chinese CHO-KLAT2.0 was slightly discrepant from the original English version on 12 items. These were all successfully adjudicated. The focus groups identified 9 new items that formed an add-on Socio-Economic Context (SEC) module for China. Linguistic improvements were made after the 2nd, 5th, 7th and 13th cognitive debriefings pairs and affected a total of 18 items. The result was a 35 item CHO-KLAT2.0 and a SEC module in Simplified Chinese, both of which have good content validity. Conclusion This detailed process proved to be extremely valuable in ensuring the items were accurately interpreted by Chinese boys with hemophilia ages ≤18 years. The need for the additional SEC module highlighted the different context that currently exists in China with regard to hemophilia care as compared to many Western countries, and will be important in tracking progress within both rural and urban China over time. Changes based on the cognitive debriefings suggest that expert verbatim translation alone is not sufficient. The Chinese version of the CHO-KLAT2.0 is well understood by boys with hemophilia in China. Next steps will be to test its construct validity and reliability in boys with hemophilia in China.

Comparative pharmacokinetics of Kogenate FS and Kovaltry in 14 Chinese paediatric patients with haemophilia A: A single-centre study Although the CL of Kogenate FS and Kovaltry showed no statistical difference in our study, the CL of Kovaltry showed a decreasing trend when compared with Kogenate (3.35 vs 3.78 mL/kg/h). Keywords: factor VIII; haemophilia A; haemorrhage; paediatric patients; pharmacokinetics EN factor VIII haemophilia A haemorrhage paediatric patients pharmacokinetics e287 e290 4 03/23/21 20210301 NES 210301 Dear Editor, Haemophilia A is an X-linked inherited bleeding disease caused by a deficiency in the activity of coagulation factor VIII (FVIII). According to the World Federation of Hemophilia (WFH), the management of haemophilia A involves prophylaxis as standard of care, especially for patients with severe haemophilia A.1 However, significant interindividual variability is observed within the patients of haemophilia A in response to treatment. [Extracted from the article]

Introduction: Turoctocog alfa is a recombinant, B domain‐truncated factor VIII (FVIII) approved for patients with haemophilia A. Aim: To evaluate the safety and efficacy of turoctocog alfa in previously untreated patients (PUPs) with severe haemophilia A. Methods: Guardian 4 was a multicentre, multinational, non‐randomized, open‐label phase 3 trial comprising a main and extension phase. The former concluded once ≥ 50 patients had received treatment for ≥ 50 exposure days (EDs) or developed inhibitors. Patients received turoctocog alfa intravenously for prevention and treatment of bleeds. The primary endpoint was the incidence rate of FVIII inhibitors (≥0.6 Bethesda Units) reported during the first 50 EDs. Results: Of the 58 patients who completed the main phase, 25 (43.1%) patients developed inhibitors (detected within 6‐24 [mean: 14.2] EDs from treatment start). High‐risk mutations were identified in 60% of patients who developed inhibitors in the main phase and were a significant predictor of inhibitor development (P =.003). Of the 21 patients who started immune tolerance induction therapy, 85.7% completed treatment with a negative inhibitor test (note that data on the last 3 patients completing ITI are based on information collated from sites prior to the final database lock). Haemostatic response (including missing values as failure) was rated as 'excellent' or 'good' for 86.1% of bleeds occurring during prophylaxis. The estimated mean annualized bleeding rate for patients on prophylaxis was 4.26 bleeds/patient/year (95% CI: 3.34 − 5.44). Conclusions: Turoctocog alfa was effective at preventing and stopping bleeds and was well tolerated. Inhibitor development was within the expected range for this PUP population. [ABSTRACT FROM AUTHOR]

In recent years, the diagnosis and treatment of hemophilic children in China has significantly improved. However, oral health conditions, which affect quality of life, haven't received attention in this population. To explore the oral health status and oral hygiene of children and adolescents with hemophilia in the Children's Hemophilia Comprehensive Care Center of China. Dental and oral hygiene examinations were performed in children and adolescents with hemophilia who visited Beijing Children's Hospital. DMFT/dmft (decayed, missing, filled teeth in permanent and primary teeth) was assessed according to World Health Organization (WHO) criteria. The simplified oral hygiene index (OHI-S) was used to evaluate the oral hygiene condition of the subjects. Questionnaires were completed by their parents. SPSS 21.0 was used for statistical analysis. A total of 114 children and adolescents were enrolled. The caries prevalence was 57.4%, 72.2% and 41.2% in primary, mixed and permanent dentitions respectively. The filling rates were 14.4%, 13.9%, and 11.4%, respectively, and the OHI-S scores of the three dentition groups were 1.49 ± 0.46, 1.57 ± 0.43, and 1.76 ± 0.46, respectively. A total of 103 valid questionnaires were collected. Sixty-nine children (67%) didn't brushed their teeth 2 times a day. Nearly half of the parents knew little about fluoride toothpaste. Multiple linear regression analysis revealed that brushing teeth with the help of parents had a significant positive impact on OHI-S. Conclusion: Dental health was unsatisfactory among hemophilic children and adolescents. The caries filling rates were low. Patients and their parents did not give much attention to oral health. What is Known: • Caries and gingivitis are the two main oral diseases that affect children with hemophilia. • However, the oral health conditions of children and adolescents with hemophilia have not received much attention in China. What is New: • This is the first study concentrating on the dental health of children with hemophilia in China. • Dental health was unsatisfactory among children and adolescents with hemophilia in China. [ABSTRACT FROM AUTHOR]

Objective: This study explores the efficacy of recombinant factor VIII (rFVIII) low-dose prophylaxis in Chinese pediatric patients with severe hemophilia A from the Retrospective Study in Chinese Pediatric Hemophilia A Patients With rFVIII Contained Regular Prophylaxis (ReCARE) population. Methods: This is additional analysis of the multicenter, retrospective ReCARE study, in which the annual bleeding rate (ABR), annual joint bleeding rate (AJBR), and safety of >12-week, low dose (10-30 IU/kg/wk) rFVIII prophylaxis divided into primary, secondary, and tertiary groups based on the joint status and joint bleeding history were analyzed. Results: A total of 57 patients (median age: 8.2 [0.4-17.3] years) from the ReCARE study receiving primary (n = 3), secondary (n = 21), and tertiary (n = 33) prophylaxes were included. Low-dose prophylaxis had significant bleeding reduction in all 3 groups compared to the baseline (S = 408.5, P < .001), with median ABR rates of −4.0 (−8.0 to −3.1), −4.0 (−24.0 to 8.0), and −13.9 (−110.6 to 20.6) in the primary, secondary, and tertiary groups, respectively, with a significant difference between the secondary and tertiary groups (P = .008). Median AJBR reduction rates were −2.3 (−6.3 to 8.4) and −14.9 (−61.5 to 19.1) in the secondary and tertiary groups, respectively. But there was no significant difference in AJBRs between the secondary and tertiary groups (P = .061), which was related to damaged joint status. Hence, longer prophylaxis was associated with better prevention of joint bleeding (P = .024). Conclusion: Despite significant ABR/AJBR reduction in all 3 groups, the efficacy of the primary prophylaxis was better than the secondary and tertiary prophylaxes. [ABSTRACT FROM AUTHOR]

Purpose Hemophilia A represents up to 80% of all hemophilia cases in China. In patients with this condition, bleeding can be prevented and controlled by administering clotting factor VIII (FVIII). Since their initial availability, recombinant FVIII products have undergone several iterations to enhance their safety. Moroctocog alfa albumin-free cell culture (AF-CC) is among the third generation of recombinant FVIII products and received regulatory approval in China in August 2012. The present study characterizes the single-dose pharmacokinetic parameters of FVIII activity (FVIII:C) after administration of moroctocog alfa (AF-CC) in male Chinese patients with hemophilia A. Methods This multicenter, open-label, single-dose study enrolled 13 male Chinese patients diagnosed with severe hemophilia A (FVIII:C <1%) and a history of at least 150 exposure-days to any FVIII-containing product. Eligible patients received a single dose of moroctocog alfa (AF-CC) 50 IU/kg IV within 10 minutes. Blood samples were collected within 2 hours before administration and through 72 hours after dosing. Findings Pharmacokinetic parameters were assessed based on FVIII:C and were analyzed by age groups: ages 6 to <12 years (n = 3) and ≥12 years (n = 10). The mean plasma concentration-time profile for FVIII:C activity was consistently lower in patients aged 6 to <12 years compared with those aged ≥12 years. Geometric AUC 0–∞ and C max were approximately 57% and 28% lower in the younger patients relative to the older patients, respectively. A total of 4 adverse events occurred in 4 patients. Low-titer, transient FVIII inhibitors were observed in 2 patients and were considered serious adverse events. Neither case resulted in clinical manifestations nor required treatment. Implications This is the first report of the pharmacokinetic parameters of FVIII:C after moroctocog alfa (AF-CC) in an all-Chinese population of males with hemophilia A. The pharmacokinetic profile in older patients was similar to that previously reported with recombinant FVIII products in studies with a predominantly white population; younger patients had reduced exposure to FVIII:C. The single doses of moroctocog alfa (AF-CC) were well tolerated; 2 cases of transient, low-titer FVIII inhibitor development were observed. ClinicalTrials.gov identifier: NCT02461992. [ABSTRACT FROM AUTHOR]