Objective:
We conducted a pilot study using a single open-ended question to elicit patient-perceived challenges and management strategies in individuals with bleeding disorders. The de-identified responses and themes expressed in this study were analyzed. The identification of perceived challenges and management strategies in individuals with bleeding disorders offers the opportunity to improve value based care.
Methods:
This retrospective, cross-sectional cohort study used a sample of convenience at The Hemophilia Center at OHSU. Study population included 20 participants. Inclusion criteria included: ages seven to eighty nine, diagnosed with a bleeding disorder and seen during any outpatient Hemophilia Center clinic visit between March 1, 2017 and April 30, 2018. Participants were included if, during the course of their clinical care, they answered the question, “What is the most significant (or greatest) challenge you have in managing your bleeding disorder and what do you do about it?” Data extracted included question response, age, type and severity of bleeding disorder. Responses were analyzed for themes by the investigators and using qualitative data analysis software. Coded demographic data was correlated.
Summary:
Seven challenge themes were identified: activity restrictions, infusions, emotion/stress, pain, future plans, education and access. Management themes included: self-advocacy, parent directed, activity modification or avoidance, acceptance, inquiry, asking for assistance, planning ahead, resiliency, and peer supports. Younger participants’ (9-17 years) challenges included activity restriction and infusions with management strategies of self-advocacy, activity avoidance and modification. Participants aged 18-57 years highlighted challenges with access to care, infusions, emotion/stress, pain, education and future planning. Management strategies in this group were focused on acceptance, planning ahead, peer support and resiliency. Analysis based on severity of bleeding disorder revealed that subjects with severe hemophilia reported infusions and activity restriction as their most significant challenge, with self-advocacy and activity modification management strategies. Participants with moderate hemophilia reported challenges centered on activity restriction and education of peers, with management strategies being self-advocacy and planning ahead. There were no differences in themes identified when analyzed based on type of bleeding disorder.
Conclusions:
This study characterizes the unique challenges and management strategies described by individuals with bleeding disorders. The themes highlighted the importance of patient voice and can be used to inform individual care decisions.
Objective:
In the PROTECT VIII phase 2/3 trial, the extended–half-life recombinant factor VIII product BAY 94-9027 provided effective bleed protection with twice-weekly, every-5th-day, and every-7th-day prophylaxis for 36 weeks. Herein, we report interim efficacy data from the PROTECT VIII extension study in patients receiving BAY 94-9027 prophylaxis for up to 5.4 years.
Methods:
In the PROTECT VIII trial, previously treated males aged 12 to 65 years with severe hemophilia A received BAY 94-9027 for 36 weeks on demand or for prophylaxis either twice weekly (30–40 IU/kg), every 5 days (45–60 IU/kg), or every 7 days (60 IU/kg). Patients could continue in the extension study using the same or a different regimen. Bleeds were recorded in electronic patient diaries, and annualized bleeding rates (ABRs) were calculated.
Summary:
Of 134 patients enrolled in PROTECT VIII, 121 patients aged 15 to 67 years (median age, 40 years) at the data cutoff (January 2018) continued in the extension with either on-demand treatment (n=14) or prophylaxis (n=107). At the time of analysis, patients had spent a median of 3.9 years (range, 297–1965 days) in the study since enrollment, with a median of 223 (range, 23–563) exposure days. Median (quartile [Q] 1; Q3) ABR for total bleeds during the extension study was 34.1 (20.3; 36.6) for on-demand patients and 1.6 (0.3; 4.6) for prophylaxis patients. Median (Q1; Q3) ABR for joint bleeds was 0.9 (0; 3.3) for prophylaxis patients during the extension. Median (Q1; Q3) ABR for total bleeds during the extension was similar for patients receiving prophylaxis twice weekly (1.7 [0.8; 3.6]; n=23), every 5 days (1.2 [0; 4.6]; n=33), and every 7 days (0.7 [0; 1.6]; n=23); among patients who switched prophylaxis frequency during the extension (n=28), total ABR was 3.1 (1.2; 6.2). Compared with the main study, ABR during the extension was further reduced in patients who remained in their treatment arm, including patients receiving prophylaxis every 7 days (median [Q1; Q3] main study ABR for total bleeds, 0.96 [0; 4.3]) . Of patients receiving prophylaxis, 20.6% had zero bleeds during the extension. No safety issues were identified.
Conclusions:
Good bleeding control was maintained with BAY 94-9027 prophylaxis with extended intervals of every 5 days and every 7 days throughout the PROTECT VIII extension study for up to >5 years.
Objective:
BAY 94-9027 is an extended–half-life recombinant factor VIII (FVIII) product. In the PROTECT VIII study, BAY 94-9027 provided effective protection against bleeds and was well tolerated with twice-weekly, every-5-day, and every-7-day prophylaxis in patients with severe hemophilia A. We report interim safety data from the PROTECT VIII extension study evaluating long-term outcomes in patients using BAY 94-9027 prophylaxis for >5 years .
Methods:
Previously treated patients aged 12 to 65 years with severe hemophilia A were enrolled in PROTECT VIII, in which they received BAY 94-9027 for 36 weeks on demand or as twice-weekly (30–40 IU/kg), every-5-day (45–60 IU/kg), or every-7-day (60 IU/kg) prophylaxis. Patients could subsequently participate in an extension study with the same or a different regimen. Adverse events (AEs), anti-PEG antibodies, inhibitor development, renal safety, and plasma PEG levels were evaluated during the extension phase.
Summary:
One hundred twenty-one of 134 patients from PROTECT VIII continued in the extension study receiving BAY 94-9027 either on demand (n=14) or as prophylaxis (n=107). At data cutoff (January 2018), patients aged 15 to 67 years at time of analysis (median age, 40 y) had a median (range) of 1420 (297–1965) days in the trial since enrollment and a median (range) of 223 (23–563) exposure days . Prophylaxis patients were treated either twice weekly (n=23), every 5 days (n=33), every 7 days (n=23), or switched frequency during the extension (n=28) . Overall, 9 patients (7.4%) experienced treatment-related AEs during the extension classified as either mild (n=4), moderate (n=4), or severe (n=1) . Two patients (1.7%) experienced 3 SAEs considered to be treatment-related (elevated liver function tests in a patient with hepatitis C ; 2 incidences of back pain); these 2 patients discontinued the study. Transient low-titer anti-PEG antibodies were detected at a single visit in 8 patients but were not associated with clinical events. No patients developed FVIII inhibitors or had sustained levels of detectable PEG in plasma . No specific changes in renal parameters were observed.
Conclusions:
During the ongoing PROTECT VIII extension, BAY 94-9027 prophylaxis was well tolerated for >5 years, and no patients developed FVIII inhibitors.
