Haemophilia prophylaxis: A model and future directions in Jordan

Dear Sir, The Haemophilia Working Group in Jordan worked diligently to propose and develop a model of prophylaxis that would be the standard of care for patients with haemophilia A in Jordan. The approach was to introduce recombinant factor VIII (FVIII) gradually and target its use initially to specific “priority” groups of patients. Four groups (A, B, C, and D) of patients with haemophilia were categorised according to the benefits that the patients would derive from prophylactic FVIII use based on their age, existing haemophilic arthropathies or joint damage, and whether they had developed inhibitors to FVIII or not. The Dutch intermediate-dose protocol, with an average dose of 20 IU/kg infused twice or three times a week in certain cases, was selected for use in all groups. The intermediate-dose protocol was considered a reasonable dosing regimen and frequency, after reviewing all the available data. Recombinant FVIII was selected as the product because the risk of transfusion-transmissible infections is lower with the use of this clotting factor than with plasma-derived concentrates which have been implicated in pathogen transmission1. According to the proposed model, group A, the first priority group, consists of all children less than 5 years old, including previously untreated patients (PUP). The rate of successful treatment was previously noted to be highest in children who began primary prophylaxis at a young age prior to any joint bleeds. This group of patients would get the greatest benefit from prophylaxis. In addition, these children would require smaller volumes of recombinant FVIII for infusion. It was, therefore, anticipated that the consumption of recombinant FVIII per patient would be less in this group and might be the most cost-effective (Table I). The projection of the working group was that Jordan would have approximately 30 patients who would fall into this “priority” group and that the estimated total consumption of recombinant FVIII for the entire group per year would be 748,800 IU (Table I). Table I Different “priority” groups of patients with haemophilia A. As for group A, it was estimated that group B would consist of approximately 30 patients aged from 5 to 15 years. However, the estimated total consumption of recombinant FVIII would be double that in group A, reaching 1,560,000 IU. Groups C and D are basically formed of adolescents over the age of 16 years. Group C comprises patients who have not developed FVIII inhibitors or arthropathy and may well benefit from prophylaxis. Group D is formed of those patients who have not developed FVIII inhibitors but do have existing active arthropathies. Therefore, group D would require more frequent doses of FVIII per week than group C. The estimated numbers of patients with haemophilia A in groups C and D in Jordan would be 12 and 8, respectively. The estimated total consumption of recombinant FVIII would be 1,123,000 IU for each of these two groups. The total number of vials of the two different strengths of FVIII was calculated in order to project how many vials would be needed on an annual basis for the country and also to have an approximate estimate of the cost of implementing the model. Clearly, the cost of the prophylaxis needs to be weighed against the presumed reduction in bleeding complications, number of hospital admissions, and joint damage, among other things, derived from the prophylactic strategy. This warrants a prospective pharmaco-economic analysis to evaluate the implementation of the programme at a national level. The working group will also consider the case of patients with haemophilia A with high-titre inhibitors to FVIII and their treatment in the future. It has been estimated that up to 30% of children with severe haemophilia A may develop antibodies against FVIII and these patients tend to have a much worse prognosis than patients without inhibitors2. The intention of the Haemophilia Working Group with its proposed model of prophylaxis was to standardise care and improve the well-being of patients with haemophilia A in Jordan. In order to implement this model of prophylaxis effectively, the working group is currently collaborating with the Ministry of Health and other healthcare institutions to educate parents and family members on how to infuse recombinant FVIII at home and to take care of the peripheral venous access site. The group is working with healthcare institutions to allow dispensation of enough FVIII for a month (based on the patients’ weight), in order to minimise the burden of travel for patients. The proposed model of prophylaxis needs to be fully adopted and endorsed by all stakeholders. Once the implementation process begins, patients with haemophilia A will start on this prophylaxis regimen according to the classification within the different groups and will be followed prospectively to evaluate the impact of the model. Standard data collection forms will be given to all members of the working group in order to collect all the necessary data in a central database, including demographics, bleeding complications, information on inhibitor development, joint status, arthropathies, hospital admissions, clinic visits, patient’s quality of life, and total consumption of recombinant FVIII on an annual basis. In addition, cost-effectiveness analyses should be conducted to examine whether instituting this model in a developing country such as Jordan would have a positive or negative outcome. Proper evaluation and feedback on an annual basis is crucial in order to convince stakeholders of its outcome and funding sustainability.