For people with hemophilia B, switching to Rixubis (nonacog gamma) as a factor IX (FIX) replacement therapy was not associated with increased bleeding rates, dose changes, adverse blood clotting events, or the development of inhibitors among patients with moderate to severe forms of the disease, according to a small observational study.
Given the limited amount of data on changing FIX replacement therapies, future surveillance studies are still needed to reassure patients and caregivers about the safety of switching medications in hemophilia B, the scientists said.
But this small study found that switching to the approved therapy Rixubis, marketed by Takeda, was not linked to any adverse effects.
The study, “A prospective surveillance study in haemophilia B patients following a population switch to recombinant factor IX (nonacog gamma),” was published in the journal Haemophilia.
Hemophilia B is a genetic condition caused by the lack or malfunction of a blood-clotting protein called factor IX, or FIX. The condition can lead to prolonged bleeding after an injury, or in some cases, spontaneous bleeding in the absence of an injury.
Bleeding may be prevented or treated with FIX replacement therapies, which work by replacing the FIX clotting protein these patients are missing.
Plasma, the clear non-cellular liquid part of blood, was the original source of the FIX protein used in replacement therapies. Yet, more recently, man-made or recombinant versions of FIX have been approved for use. These recombinant versions typically are associated with a lower risk of infections from human blood-derived microorganisms.
As part of Canada’s public healthcare system, the province of Quebec recently switched most patients with moderate or severe hemophilia B to Rixubis, a recombinant FIX replacement therapy, following its approval in the country.
Now, researchers at the Centre Hospitalier Universitaire Sainte-Justine, in Montréal, and their colleagues are reporting data from a surveillance study that was designed to compare patients’ outcomes before and after switching to Rixubis.
The participants completed three visits for clinical analysis and blood collection before and 30 minutes after receiving FIX infusions. The first visit occurred while they were on their previous FIX therapy, the second when receiving the first infusion of Rixubis, and the third and last visit after being on Rixubis for two to more than 150 days.
The analysis included 31 male patients, of whom 23 were adults and eight were children. Nearly all (90.3%) had severe hemophilia B, with 83.9% on prophylaxis, or preventive treatment. Those receiving preventive treatment used 7 to 111 international units (IU) of FIX per kilogram of body weight (IU/kg), one to seven times per week.
Before switching, most adults (78.3%) were treated with BeneFIX, a recombinant FIX replacement therapy, at a dose of 8 to 111 IU/kg. Meanwhile, 21.7% were treated with Immunine, a plasma-derived FIX replacement therapy, at a dose ranging from 7 to 46 IU/kg. All of the children were treated with BeneFIX at doses ranging from 28 to 103 IU/kg. Three adults had less than 150 exposure days before switching.
The team found no significant differences in blood levels of FIX between visits or between children and adults. Of the five adults on plasma-derived Immunine, there also were no significant differences noted between visits.
Altogether among the participants, 25 had information on bleeding episodes for at least eight months before and after switching to Rixubis. In adults, the mean annual bleeding rate (ABR) in joints did not significantly differ before and after the switch, “suggesting that their treatment remained effective after the switch to control bleeding in joints,” the team wrote.
Similar rates were reported for adults who switched from Immunine, as well as for bleeds occurring in non-joint locations.
In contrast, children ages 4–14 had significantly higher non-joint ABRs after the switch than before, especially the youngest. Most of these bleeds were minor, injury-related bleeds that were resolved within 24 hours of treatment with minimal pain, swelling, or movement restriction.
No increased doses were required between visits in most cases, and no changes in mean FIX consumption were noted in adults or children. No differences were found in markers for excess blood clotting (APTT and D-dimer), a concern with FIX therapies, and no blood clotting events were recorded before and after the switch.
Before switching to Rixubis, none of the patients had a reported history of inhibitors, which are self-made antibodies that can target and neutralize the FIX protein within replacement therapies, reducing their effectiveness.
After switching from BeneFIX to Rixubis, one adult and three children with severe disease tested positive for these antibodies. Yet, further analysis revealed these antibodies were not specific to FIX, suggesting they may have been related to the FIX production process.
“Our small observational study confirms that product switching in HB [hemophilia B] is not associated with an increased risk of adverse events, such as bleeding, inhibitors, and thrombotic events,” the investigators wrote.
“Given that few studies on FIX switching are available, it is of interest to conduct surveillance studies to reassure patients and caregivers and provide useful information to health authorities for future tenders,” they concluded.
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