Prophylactic vs On-Demand Therapy

Prophylactic vs On-Demand Therapy

People with mild hemophilia and most persons with moderate hemophilia are treated with coagulation replacement therapy "on demand" (as needed) to stop bleeding that cannot be controlled simply by applying pressure to the wound. Children with severe hemophilia tend to receive replacement therapy a few times a week to prevent bleeding before it starts (prophylactic therapy). As they reach adulthood, they tend to switch to on-demand treatment for a variety of reasons, including conflicts with their school or work schedules, the inconvenience of seeing their doctors or going to a clinic two to four times a week, and the expense of continuous prophylactic therapy. But prophylactic therapy has obvious advantages, even for adults with severe hemophilia, including prevention of permanent joint damage due to repeated episodes of bleeding into the joints.

How often a person with hemophilia should receive factor replacement therapy is an open-ended question. The answer depends upon how severe the hemophilia is, how serious the patient is about sticking to a treatment schedule, and how effective replacement therapy is for that particular individual. What works for one person will not necessarily work for another.

Advantages of prophylactic therapy. The Joint Outcome Study involved 65 boys with hemophilia A who had little or no joint bleeding and who were under 2½ years of age. Boys in the prophylactic therapy group were given recombinant factor VIII (rFVIII) every other day; boys in the on-demand group were given a dose of rFVIII during each bleeding episode and then half that dose 1 and 3 days later. Boys in the prophylactic group had significantly less bleeding than did those in the on-demand group. Further, as the boys grew older and more active, those given prophylaxis experienced significantly less joint bleeding. When magnetic resonance imaging was done at age 6 years in 56 of the boys, no joint damage was found in 93% of the children given prophylaxis and 55% of those given on-demand treatment.

The ESPRIT study involved 40 boys (average age, 48 to 50 months) with hemophilia A but no evidence of prior joint damage who were given either prophylactic or on-demand rFVIII therapy. The children were treated based upon the factor VIII level in their blood. Boys who received prophylactic therapy had fewer bleeding episodes and fewer signs of joint damage on x-ray than did those given on-demand treatment. The two groups also reported a significant difference in their quality of life: Boys given on-demand rFVIII treatment felt more overprotected than did those given prophylaxis.

The multinational SPINART study is following 84 adults with severe hemophilia receiving either high-dose prophylactic therapy three times a week or on-demand treatment when a bleeding episode occurs. After nearly 17 months, those receiving prophylaxis have shown a 93% decrease in bleeding rate. In addition, the results suggested that bleeding of persons receiving prophylactic therapy was less severe.

Bypassing inhibitors. A product that may be helpful to persons born with hemophilia who have developed inhibitors to factor replacement therapy is being tested for on-demand therapy. Researchers studied the use of Factor Eight Inhibitor Bypass Activity Nanofiltered (FEIBA NF) in 36 persons with hemophilia A or B who had developed inhibitors to replacement factors. FEIBA NF was given as prophylactic therapy to 17 persons and on demand for bleeding to the remaining 19 people. The on-demand group had about three times as many bleeding episodes as did the prophylactic therapy group. Further, the prophylaxis group averaged about one third the number of bleeding episodes over a year as did those in the on-demand group. Bleeding of a new joint occurred in one third as many individuals in the prophylaxis group as in the on-demand group. Only one fourth of the adverse events reported were believed to be related to the use of FEIBA NF.

What Does This Mean to People With Hemophilia?

In 1958, doctors realized that moderate hemophilia was less likely to be associated with disabling joint disease than was severe disease. Therefore, doctors started trying to prevent bleeding episodes in children with hemophilia by giving them prophylactic factor replacement therapy rather than waiting for a bleeding episode to occur.

Many studies have suggested that prophylactic factor replacement therapy is more effective than on-demand therapy for treating severe hemophilia. Overall, when prophylaxis is started before a child reaches 3 years of age, joint damage is avoided. However, prophylaxis is more time-consuming and expensive than is on-demand therapy. Further, those receiving prophylactic therapy may have a catheter or a device called a Port-A-Cath® inserted into a vein to make it easier to receive repeated infusions (injections) of replacement factor; however, placement of these devices increases the risk of complications.

FEIBA NF is an important new blood product that may help persons who develop inhibitors to factor replacement therapy. Prophylactic therapy with FEIBA NF may reduce the risk of annual bleeding events by almost 75% in people with hemophilia who have developed inhibitors to conventional factor replacement therapy.

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