Patients Express Gains in Switch to Extended Half-life Therapies
For some patients with moderate or severe hemophilia, switching from standard to extended half-life replacement therapy results in improvements in key outcome measures, a study in Canada found.
Most of these self-reported gains in health-related quality of life, and physical, mental, and social functioning three months after the switch, however, had dissipated at two years.
Still, a majority of the people who began using the extended half-life therapies in this study continued to express a preference for them. This finding indicates potential limits to the questionnaires used in patient-reported outcomes, most of which were developed before these longer-lasting treatments became available, its researchers wrote.
The study, “The impact of extended half-life factor concentrates on patient reported health outcome measures in persons with hemophilia A and hemophilia B,” was published in the journal Research and Practice in Thrombosis and Haemostasis.
Hemophilia is caused by defective or missing clotting factors that promote blood clotting. The type of hemophilia depends on the clotting factor that is defective or missing.
Replacement therapy works by replacing those specific clotting factors. However, standard products require frequent infusions to maintain sufficient clotting factor levels for longer periods of time.
Recently, so-called extended half-life products have been developed in an attempt to overcome this limitation. In these products, the structure of the delivered clotting factor is changed so that the body takes longer to clear it from circulation. This means that these products work for longer periods of time after being infused into the bloodstream.
One way of changing the structure of clotting factors so that they last longer in circulation is to fuse them with the Fc region of an antibody. This makes treatment last for days or weeks instead of hours. Two such products are Eloctate (recombinant factor VIII) for hemophilia A, and Alprolix (recombinant factor IX) for hemophilia B.
However, “it is unclear how switches from standard to extended half-life factor affect patient-reported outcomes,” the researchers wrote.
The scientists set out to evaluate if outcome measures improved in hemophilia patients who switched from standard to extended half-life products, as captured through disease-relevant questionnaires. They specifically focused on Eloctate and Alprolix, which “were the first and only available” in Canada from 2016 to 2018, the period reviewed.
Their study recruited 58 patients, mostly adults, at eight major hemophilia centers in Canada. Of them, 25 switched to extended half-life products (16 to Eloctate and nine to Alprolix) and 33 remained on standard half-life products.
Compared with non-switchers, switchers were older and had more bleeding episodes in the year prior to enrolling in the study.
Health-related quality of life was measured using two questionnaires: the Hemophilia-specific Quality of Life (Haem-A-QoL) questionnaire and the 36-Item Short-Form (SF-36) survey. Measures were collected at the study’s beginning (baseline) and again after three, 12, and 24 months.
Patients who switched to extended half-life products saw their overall health-related quality of life improve at three months after the switch. Those who moved to Eloctate had a mean reduction of 2.3 points on Haem-A-QoL, while those who switched to Alprolix had a mean reduction of 5.0 points (lower scores indicate a better quality of life).
In both groups, however, these self-reported gains largely stopped at two years of use, which the researchers suggested was due to a “ceiling effect” of treatment.
Among non-switchers, those with hemophilia B — but not those with hemophilia A — also saw improvements in overall health-related life quality, with a mean reduction of 4.6 points on Haem-A-QoL.
Results of the SF-36 survey were, in part, similar.
Other improvements at three months were seen in physical functioning and activities, mental health, and social functioning. Treatment satisfaction also improved among switchers to Eloctate, while chronic pain and the ability to engage in daily activities improved among those who moved to Alprolix.
While these findings reveal limits to perceived improvements using patient-reported outcome measures, “current tools and ceiling effects limit the perceived impact,” the researchers wrote.
“What is perhaps more powerful is the end-of-study patient preference questionnaire, where 15 of 16 switchers indicated their preference for EHL [extended half-life] over SHL [standard half-life] concentrates,” they added.
To better understand how extended half-life products influence health-related quality of life and other measures key to hemophilia patients, improved self-reporting tools will be needed, the researchers noted.