Low Dose Prophylaxis in Hemophilia Care

Abstract

Hemophilia is an inherited bleeding disorder which causes impaired blood clotting. The severity of disease depends on the type of Hemophilia, level of clotting factor concentrate (CFC), phenotypic heterogeneity and the development of inhibitors. The currently accepted standard of care of this disease is prophylaxis therapy (PT) with CFC. Prophylaxis therapy for Hemophilia is given in developed countries for the last few decades. On the contrary, episodic therapy (ET) is still the mode of treatment in middle and low income countries. ET is documented to have several potential risks such as increased bleeding rate, disability due to haemarthrosis, poor quality of life and increased chances of mortality. Several studies conducted in developed countries have confirmed the clinical efficacy of PT in Hemophilia treatment. Currently, there exist several challenges for implementation of this effective treatment in resource poor nations. Low dose prophylaxis (LDP) has been developed as a solution to minimize these challenges and to provide better care for subjects with Hemophilia from low resource countries. The impact of LDP was evaluated by several recent studies and the reported clinical outcomes seem to suggest an optimistic future for this line of therapy. Several themes related to Hemophilia care like inhibitor development, tolerance, pharmacokinetics of CFCs and cost-benefit analysis of different prophylaxis regimens are currently understood poorly. These distinct elements are highly relevant to assess the actual benefits of LDP regimen in a global scale.

Feasibility and outcomes of low‐dose and low‐frequency prophylaxis with recombinant extended half‐life products (Fc‐rFVIII and Fc‐rFIX) in Ivorian children with hemophilia: Two‐year experience in the setting of World Federation of Haemophilia humanitarian aid programme

“…This is particularly valuable and supports early prophylaxis considering 56% of the participants had a total HJHS score at 0 at the initiation of prophylaxis, the strong correlation established between the ASJBR and the HJHS scores and that the goal of prophylaxis is to preserve joint health 21 . Our results are consistent with what has already been reported in China, India and Tunisia 6‐9 . These data are even more relevant as the frequency of injections was limited (1 per week for Fc‐rFVIII and one every 10 days for Fc‐rFIX) and despite the significant prophylaxis dose reduction resulting of the participants' weight gain over the study period.…”

“…21 Our results are consistent with what has already been reported in China, India and Tunisia. [6][7][8][9] These data are even more relevant as the the key factor to successfully prevent bleedings in severe haemophilia. 10 In our study, adherence difficulties had a significant impact on ASJBR and were primarily related to the parents' low education level.…”

“…In resource‐constraint countries, prophylaxis is not affordable at conventional regimens as access to clotting factor concentrates (CFCs) is often extremely limited 5 . In several resource‐limited countries (China, India, Tunisia), low‐dose prophylaxis in children has demonstrated its feasibility and advantages over on‐demand therapy 6‐9 . Besides CFCs supply, success of prophylaxis is conditioned by adherence that requires education of patients and families 10 and is facilitated by home therapy 1 …”

Impact of humanitarian aid linked prophylaxis in Côte d'Ivoire (Ivory Coast)

“…14 positive incremental progress measured year over year, both globally and within countries. 1,[15][16][17][18] Over the long term, some form of genetic therapy may be a likely successor to the humanitarian aid programme, 19 and may result in a cure or partial cure to alleviate the misery and death of severe and severely moderate haemophilia in resource constrained countries.…”

“…The challenges may at times feel insurmountable, but as the study in Côte d'Ivoire shows, progress occurs via one study, one country at a time. The WFH vision remains ‘Treatment for All’, with positive incremental progress measured year over year, both globally and within countries 1,15‐18 …”