Is Continuous Low-Dose Prophylaxis Superior to On-Demand Treatment for Patients with Hemophilia?

Abstract

Long-term (or continuous) prophylaxis is generally accepted as the best form of treatment for patients with severe hemophilia A and B. Results of recent prospective, randomized clinical trials, as well as observational studies performed in the last decades, have provided strong and convincing evidence that continuous prophylaxis leads to reduction in the number of bleeding episodes, better joint status and improved health-related quality of life as compared with on-demand (or episodic) treatment. Nevertheless, many questions regarding long-term prophylaxis still remain open, for instance: when should prophylaxis be started (before or after the first joint bleeding), what is the optimal dosage to replace the missing factor, when should discontinuation of long-term prophylaxis be considered, what is the best way to measure the outcome of prophylaxis, etc. Moreover, there are numerous obstacles to widespread use of prophylactic therapy. The most challenging seem to be adequate venous access (particularly in younger patients) and patients' adherence. The crucial barrier to long-term prophylaxis is, however, the remarkably high cost of clotting factor concentrates. For most countries high-dose or intermediate-dose prophylaxis regimens are not affordable due to lack of economic resources. So, is continuous prophylaxis reserved exclusively for wealthy societies? Fortunately, there is an increasing body of evidence to suggest that low-dose prophylaxis offers significant benefits over on-demand treatment with comparable amounts of factor concentrate (and much lower amounts if compared with intermediate or high-dose prophylaxis regimens). The aim of this article is to discuss the clinical and economical aspects of continuous prophylaxis in hemophilia with emphasis on the low-dose regimens.