Study Examines Changes in Hemophilia Prescribing Practices Since 1999

A recent study examined changing trends in prescribing practices among US hemophilia specialists since 1999.

The researchers said they did the study because the specific dosing regimens of treatments prescribed by blood specialists have not been widely analyzed. They surveyed members of the Hemostasis and Thrombosis Research Society via paper surveys at its in-person annual symposia in 1999 and 2015, followed by an online survey in 2021.

The surveys collected information on hemophilia treatments including factor dosing, inhibitor therapy, and gene therapy. During the timeframe of the study (1991 to 2021), new products entered the market. In 1999, the new therapies were standard half-life factor products, made with recombinant DNA, which reduced the potential for exposure to infectious agents.

By 2015, the novel therapies were extended half-life (EHL) products, followed by emicizumab, a non-factor replacement therapy, in 2021. Emicizumab is a bispecific humanized monoclonal antibody that restores the function of missing activated factor (F)VIII by bridging FIX (FIX) and FX in hemophilia A (HA). It was approved in 2017 for patients with inhibitors and in 2018 for those without inhibitors.

In addition, the 2021 survey included a question about gene therapy.

Results showed that more specialists are seeing patients with hemophilia. Providers treating hemophilia for more than 50% of their practice time rose from 37.5% of respondents in 1999 to 46.3% in 2021.

Adults cared for in a practice rose from 52.5% over the study period, and pediatric patients rose 42.3%.

Dosing practices have trended upward, particularly for hemophilia B (HB), and especially for patients who experience major life-threatening bleeds.

For major life-threatening bleed dosing, the percentage of clinicians who prescribed ≥56 units/kg of FVIII varied from 5.1% in 1999 to 23.1% in 2015 and to 19.5% in 2021.

Specialists prescribing factor concentrates at >40 units/kg for routine bleeding events rose from 0% in 1999 to 29.3% in 2021 in HA and from 22.5% to 87.8% in HB.

In 2021, providers said they prescribed emicizumab to treat patients with HA (>89.5% pediatric, >85.7% adult) with or without inhibitors at least some of the time.

Primary prophylaxis is the predominant treatment regime for patients less than 4 years of age, with long-term secondary prophylaxis more than doubling during the study period, from 12.5% of providers in 1999 to 42.5% in 2021.

Clinicians reported that the number of patients on immune tolerance induction therapy, where a patient with inhibitors are given large doses of factor concentrate to induce tolerace, are lower than before, possibly due to the introduction of emicizumab.

Most providers prescribed emicizumab to their patients with inhibitors to HA, and a smaller number prescribed it for patients with HA patients without inhibitors.

Most specialists (78.0%) said they expected to recommend gene therapy at least some of time. About half (48.8%) of clinicians would recommend gene therapy to at least half their patients that successfully pass the screening tests.

The researchers recommended that additional studies compare clinician prescribing with patient use patterns for newer therapies, and to pay close attention to outcome evaluation.

Reference

Curtis R, Roberts JC, Crook N, et al. Trends in prescribing practices for management of haemophilia: 1999–2021. Haemophilia. Published online March 15, 2023. doi:10.1111/hae.14769