Safety and Efficacy of Benefix in Patients With Hemophilia B in Usual Care Settings in China

Factor IX (FIX) inhibitor development was defined as any Bethesda inhibitor titer greater than the laboratory's normal range or Bethesda inhibitor titer >=0.6 Bethesda Unit (BU)/mL.

FIX product allergy was defined as a hypersensitivity reaction to a FIX product with symptoms such as hives, urticaria, tightness of chest, wheezing, hypotension, and anaphylaxis based on investigator's judgments.

Thrombotic event was defined as any event associated with formation of a blood clot including catheter-associated thrombi and thrombotic complications.

An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of the causality with the treatment or usage. A serious adverse event (SAE) was any untoward occurrence at any dose that resulted in death; was life threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both serious and non-serious AEs. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study drug.

For prophylaxis period, annualized bleeding rate (ABR) was derived for each participant by the following formula: ABR = number of bleeds in prophylaxis period / (number of days in prophylaxis period/365.25). A prophylaxis period was defined as time from first prophylaxis infusion through 6 calendar days after the day of last prophylaxis infusion, or the day of study conclusion visit, whichever was earlier. A break in the prophylaxis period was any period of 28 days or longer in which no prophylaxis infusions were given. For a prophylaxis regimen to have been qualified to have ABR calculated, the sum of its periods needed to be >=14 days.

The prophylaxis infusion time, bleed start time and bleed type (etiology) were used to determine the number of spontaneous, non-traumatic breakthrough bleeds that occurred <=48 hours after a prophylaxis infusion. If there was more than 1 bleed location (eg, ankle and joint) with identical bleed start date and time, it was treated as 1 bleed occurrence.

For on-demand period, the annualized bleeding rate (ABR) was derived for each participant by the following formula: ABR = number of bleeds in on-demand period / (number of days in on-demand period/365.25). The on-demand period was defined as the entire time of enrollment in the study (ie, from the date of the enrollment visit through the day before the Final/Early Termination visit) except time in any prophylaxis period. The breaks in the prophylaxis period were considered on-demand periods. For an on-demand regimen to have been qualified to have ABR calculated, the sum of its periods needed to be >= 14 days.

Response was assessed using 4-point On-Demand Hemostasis Efficacy Rating Scale. Excellent means definite pain relief and/or improvement in signs of bleeding starting within 8 hours after an infusion, with no additional infusion administered; good means definite pain relief and/or improvement in signs of bleeding starting within 8 hours after an infusion, with at least one additional infusion administered for complete resolution of the bleeding episode, or definite pain relief and/or improvement in signs of bleeding starting after 8 hours following the infusion, with no additional infusion administered; moderate means probable or slight improvement starting after 8 hours following the infusion, with at least one additional infusion administered for complete resolution of the bleeding episode; no response means no improvement between infusions or during the 24 hour interval following an infusion, or condition worsens. Both first infusions and follow-up infusions were included.

The number of BeneFIX infusions administered to treat each new bleed was calculated by adding the on-demand initial treatment and any on-demand follow-up treatments for the same bleed. If there was more than one bleed location (eg, ankle and joint) with identical bleed start date and time, it was treated as one bleed occurrence.

The total amount (international units [IU]) infused for each BeneFIX infusion was summed to calculate the total factor IX consumption for each participant. The average infusion dose for each participant was calculated as his total factor IX consumption (in IU) divided by the number of infusions administered.

The total amount (international units [IU]) infused for each BeneFIX infusion was summed to calculate the total factor IX consumption for each participant. The average infusion dose for each participant was calculated as his total factor IX consumption (in IU) divided by the number of infusions administered.

The total amount (international units [IU]) infused for each BeneFIX infusion was summed to calculate the total factor IX consumption for each participant. The average infusion dose for each participant was calculated as his total factor IX consumption (in IU) divided by the number of infusions administered.

Less than expected therapeutic effect (LETE) in the on-demand setting was defined as 2 successive "no response" ratings recorded after 2 successive BeneFIX drug infusions, respectively.

Less than expected therapeutic effect (LETE) in the prophylaxis setting was defined as occurrence of any spontaneous bleed within 48 hours after a regularly scheduled prophylactic dose of BeneFIX (which was not used to treat a bleed).