Factor dosing increases, prophylaxis use highlight treatment changes

Hemophilia specialists surveyed to document how prescription practices vary, impact of new therapies

Joana Vindeirinho,PhD avatar

by Joana Vindeirinho,PhD |

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Higher replacement factor doses and the use of preventive treatments are just two ways prescription practices for hemophilia have changed over time, according to a survey of specialists over 22 years.

The surveys also show the impact of Hemlibra’s (emicizumab-KXWH) approval and showcase the expectations for gene therapy, which many clinicians say they will recommend to their patients.

“Our comparison of [hemophilia] prescribing patterns during the 22-year period indicates changes in treatment patterns over time. As novel therapies … enter the market, repetition of this survey will help to inform clinicians, patient advocates, and policy makers of current and future US prescribing patterns,” the researchers wrote in “Trends in prescribing practices for management of haemophilia: 1999–2021,” which was published in Haemophilia.

Hemophilia is a bleeding disorder caused by low levels of certain clotting factors — proteins crucial for blood clots to form. This leads to prolonged and excessive bleeding. The most common types of hemophilia are hemophilia A, which is associated with low clotting factor VIII levels, and hemophilia B, caused by low levels of factor IX.

The main treatment for hemophilia consists of replacement therapy, wherein patients receive a version of the clotting factor they are missing. Newer replacement therapies have an extended half-life, meaning they last longer and patients require less frequent dosing.

Antibodies against clotting factors can develop, however. Known as inhibitors, they can greatly reduce these therapies’ effectiveness. Some treatments, such as bypassing agents, can overcome the limitations posed by inhibitors.

The recent approval of Hemlibra has changed the preventive (prophylaxis) landscape for hemophilia A patients. Because Hemlibra is an antibody that’s designed to mimic the actions of factor VIII, it isn’t affected by inhibitors that can render standard replacement therapies ineffective.

Researchers in the U.S. surveyed hemophilia specialists in 1999, 2015, and 2021 to document how prescription practices vary and the impact of new therapies.

The 1999 and 2015 surveys queried clinicians at a U.S. hemophilia treatment center (HTC) and attended annual conventions of the Hemostasis and Thrombosis Research Society (HTRS) in those years. The 2021 online survey sampled HTRS members who studied bleeding stoppages and blood clotting. The surveys reflect changes in the therapeutic landscape and take into account the approval of Hemlibra and the expected use of gene therapy.

There were 41 respondents in 1999 and 2021, and 53 in 2015. Most were physicians, with nurses also participating in the 2015 and 2021 surveys.

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Changes in prescription practices for treating hemophilia

The average number of patients cared for in respondents’ clinics rose from 1999 to 2021, increasing by 52.5% for adults and 42.3% for children. Similarly, the proportion of respondents who said they dedicated more than 50% of their workload to hemophilia patients rose from 37.5% in 1999 to 46.4% in 2021.

Over the study period, the proportion of respondents who prescribed replacement factor doses of more than 40 units per kilogram of body weight for routine bleeds increased from 0% in 1999 to 29.3% in 2021 for hemophilia A and from 22.5% to 87.8% for hemophilia B. Doses for treating life-threatening bleeds in both types also increased.

The proportion of respondents prescribing primary prophylaxis (before repeated bleeding occurs) to children younger than 4 “all of the time” increased from 22.2% in 1999 to 86.5% in 2021. Secondary prophylaxis (after damage caused by repeated bleeding has occurred) prescriptions to any patient “all of the time” increased from 12.5% in 1999 to 42.5% in 2021.

Impact of Hemlibra, gene therapy on hemophilia treatment

Anti-inhibitor therapy prescriptions declined from 2015 to 2021, possibly due to Hemlibra. In the 2021 survey, more than 90% of respondents prescribed Hemlibra to their hemophilia A patients with inhibitors, with 63.2% prescribing Hemlibra “all of the time” to children and 57.1% to adults.

Hemlibra use in hemophilia A patients without inhibitors was also widespread, with more than 80% of clinicians prescribing it. The proportion of respondents prescribing it “all of the time” in these patients was low (13.2% in children, 5.7% in adults), however.

Almost 40% of clinicians had patients enrolled in gene therapy trials and 78% said they would recommend gene therapy to those eligible for it, with responses distributed between a quarter of the time to all the time.

While the changes in prescription practices are mainly due to new therapeutic choices, the researchers noted the possible influence of insurance policies and the move toward a treatment goal of “life without bleeds.”

“Decision makers in the public and private sector need to take these changes into account when budgeting for the care of [people with hemophilia]. Clinical managers may also want to use these findings when planning for staffing levels,” the researchers wrote, who said future studies could better understand prescription trends and their impact by including patient outcomes and how the therapies are used, as well as comparisons with other countries.