Extended Half-life Products Linked to Fewer Infusions, Low Bleed Rates
For boys and men with moderate to severe hemophilia, switching to extended half-life (EHL) products is linked to a reduced number of infusions and a sustained low rate of bleeds, according to a real-life, multi-center study in Canada.
Notably, a significant drop in the annualized bleeding rate (ABR) was observed with EHL products only in children with hemophilia A. The absence of such significant reductions in other patient subgroups may be related to the already low bleeding rates observed with standard products before a treatment switch, according to the researchers.
Further analysis on patient-reported outcomes may help to better capture the effect of these extended half-life products in the lives of hemophilia patients, the researchers noted.
Such EHL products — blood-clotting factor products that are equally efficient with less frequent need for injections — did not become available in Canada until 2016.
The study, “Factor product utilization and health outcomes in patients with haemophilia A and B on extended half-life concentrates: A Canadian observational study of real-world outcomes,” was published in the journal Haemophilia.
About 80% of hemophilia patients have a deficiency in clotting factor VIII (FVIII) — classifying them as having hemophilia A — and the other 20% have a deficiency in clotting factor IX, known as FIX. Individuals with missing or defective factor IX are diagnosed with hemophilia B.
The mainstay prophylactic, or preventive, treatment for patients with severe hemophilia is the replacement of the missing clotting factor for that particular type of the blood disorder.
Compared with standard half-life factor concentrates, EHL products take longer to be broken down by the body. That longer half-life has been associated with less frequent infusions, prolonged protection from bleeds, and improved patient compliance with prescribed treatments.
However, evidence from the real-life use of EHL products remains limited.
To learn more, researchers in Canada evaluated the change in annualized factor use in boys and men with moderate to severe hemophilia who switched to EHL products after they became available in the country in January 2016.
A total of 125 switchers — 93 with hemophilia A and 32 with hemophilia B — were recruited across eight major Canadian hemophilia treatment centers between April 2016 and June 2018. For comparison, the study also enrolled 33 non-switchers, which included 27 patients with hemophilia A and six with hemophilia B.
Data on all of the patients’ use of clotting factors, and their annualized bleeding rates, were collected at their entry into the study, and after one and two years.
The median age for hemophilia A patients was 17, and 38 for those with hemophilia B. A total of 51% of hemophilia A switchers were younger than age 18 at the time of their enrollment. Prior to the switch, 95% of hemophilia A patients and 81% of hemophilia B patients were on prophylaxis.
Switchers appeared to have more severe disease than non-switchers, but the small number of non-switchers prevented meaningful comparisons between the two groups, the team noted.
The results showed that there was a significant reduction in the prescribed weekly prophylactic dose after the switch to EHL products for both boys (by 14%) and men (by 8%). Prescribed weekly prophylactic doses also dropped significantly — by 44% — in patients of all ages with hemophilia B.
Switching to EHL also was associated with a stabilization of actual annualized factor use — as assessed through available infusion diaries — in men with hemophilia A. A non-significant, 7% drop in this rate was seen in boys with that disease type.
Among hemophilia B patients, actual median annualized FIX use was significantly reduced by 15% in adults. It also declined, non-significantly, by 16% in children with hemophilia B.
Changes in the preventive regimen also suggested that hemophilia patients, in general, received a median of one less factor infusion per week after switching to extended half-life products.
These findings highlighted “a concurrent significant reduction in the prescribed weekly prophylactic dose and observed annualized FIX utilization in all ages who switched to [EHL],” the researchers wrote.
In contrast, switching to extended half-life FVIII — for hemophilia A patients — was associated “with a smaller reduction in the annualized FVIII utilization in the paediatric subgroup only,” they added.
Notably, given that the incompleteness of infusion records was more common in the pre-switch than in the post-switch period, the researchers hypothesized that the real reduction in factor utilization was even greater than that observed in this study.
Moreover, the median ABR dropped from 1 to 0.5 among pediatric switchers, but this reduction only reached statistical significance in boys with hemophilia A. In adults, the median ABR remained low and stable before and after the switch.
The median annualized joint bleed rate remained close to zero among hemophilia A and B patients and the proportion of patients with zero bleeds remained similar between pre- and post-switch periods.
The data indicate that the overall ABR “remained low pre-/post-switch with a statistically significant reduction in the median ABR detected only in [hemophilia A] paediatric switchers,” the team wrote.
The researchers also hypothesized that the absence of statistically significant drops in the ABRs among other subgroups may be due to the already low rates pre-switch, and to the small number of included patients, which might have limited the detection of significant differences.
Among patients who did not switch to EHL, both median annualized factor usage and the bleeding rate remained stable in the two-year observational period, compared with the year prior to study entry.
The most common reasons cited for the product switch, according to researchers, included the need for fewer infusions to reduce the patient’s treatment burden. Other cited reasons were patient/family preference, high ABR, poor adherence to standard half-life products, and improved quality of life.
Four patients who switches — two with each type of hemophilia — decided to return to the use of standard products, due to increased bleeding/bruising tendency or frequent headaches.
Overall, “switching from [standard half-life] to EHL products led to a small reduction in factor utilization, while preserving a low ABR in children and adults with hemophilia,” the researchers wrote.
The team now plans to publish patient-reported outcome data from the study participants, which they hope will lead to a better understanding of how extended half-life products affect Canadian hemophilia patients, their families, and the public payer.