Show me the evidence: Effectiveness of low‐dose prophylaxis

Abstract

Prophylaxis is the gold standard for haemophilia treatment, by reducing bleeding events and improving joint status and quality of life. 1 In fact, it does require more amount of clotting factor concentrates than for on-demand treatment, and so a higher cost, that could represent a barrier to introduce prophylaxis in countries with limited resources. In emerging countries, efficiency of prophylaxis was also demonstrated. 2 If we consider the history of prophylaxis, low-dose prophylaxis is the first step of prophylaxis. 3 In the 1960s, Swedish started prophylaxis with low doses, and then, the evolution of the regimen led to gradually intensified prophylaxis protocols, with the aim of zero bleed, and early start. Low-dose prophylaxis is an alternative that could be effective and recommended for countries with limited resources. 4 Is low-dose prophylaxis acceptable nowadays? In countries where on-demand therapy is the treatment option, because full-dose prophylaxis could not be applied, low-dose prophylaxis should be considered, at least for children, as a first step. There are data of evidence showing the superiority of low-dose prophylaxis than episodic treatment. Low-dose prophylaxis has positive outcomes with improvement of quality of life and reduction ofbleeding events. Moreover, Srivastava 4 reported calculations of no increase of used clotting factor concentrates. Outcome measurements should be used in order to have objective data of the effectiveness of low-dose prophylaxis. Annual bleeding rate and Haemophilia Joint Health score are the easier and cost effective tools. Many countries such as China, 5 India, 6 Tunisia, 7 Thailand, 8 Indonesia, 9 Algeria and Egypt practise low-dose prophylaxis as a primary, secondary or tertiary prophylaxis. Published studies on low-dose prophylaxis have shown superiority of such protocol over episodic treatment in terms of bleed reduction, and quality of life, with improved physical activity, inde-Correspondence AbstractProphylaxis is the gold standard treatment for haemophilia but requires more amount of clotting factor concentrates, than on demand therapy. Low dose prophylaxis is an alternative for countries with limited resources. There are data of evidence showing the superiority of low-dose prophylaxis than episodic treatment. Studies from China, India, Tunisia, Thailand and Indonesia reported experiences with low dose prophylaxis using outcome assessment. These studies have shown the effectiveness of various protocols regimen with once, twice or thrice injection of 10-15 UI Kg-1 per injection. These protocols allow reduction of joint bleeds and at least delay of joint damages. There is not enough long-term data nowadays, but low dose prophylaxis is certainly better than on demand therapy and should be considered as a first step of prophylaxis in some countries but not the final goal. K E Y W O R D SLow dose prophylaxis, Hemophilia, Prophylaxis, Hemophilia joint health score

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 …”

Is immune tolerance induction conceivable in haemophilia with inhibitors in a low‐middle income country? Real‐world data from Tunisia

“…Nonetheless, low-dose prophylaxis has proven effective in many LMICs, including Tunisia. 1,2 One of the challenges jeopardizing haemophilia treatment is the development of inhibitors. Those neutralizing antibodies against factor VIII (FVIII) affect up to 30% of patients with severe haemophilia A (HA).…”

Hemophilia gene therapy—New country initiatives

“…St Jude has embarked on evaluating the feasibility of implementing AAV‐mediated gene therapy for haemophilia in LMIC. The hypothesis is that setting up HTCs in LMIC for administration and monitoring of AAV‐mediated gene therapy is operationally feasible, cost‐effective in comparison to standard‐ or low‐dose prophylaxis or various availability of on‐demand therapy, 4,81 and safe and effective in improving the health and quality of life of patients with haemophilia. The primary aim will investigate feasibility by measuring a composite endpoint of successful vector management (documentation of chain of custody, proper storage and handling, and formulation of vector product for infusion), satisfactory administration to the patient and appropriate follow‐up monitoring during the initial months postvector infusion (completion of visits, monitoring of factor levels and the adequate interpretation of liver function tests with regard to potential vector‐induced transaminitis).…”