Research Studies

Objective:

To evaluate changes in healthcare resource utilization and haemophilia related events among patients diagnosed with haemophilia A between 2008 and 2012.

Methods:

This retrospective study analyzed data from the Humedica de-identified electronic medical record database between January 2008 and December 2012. Male patients diagnosed with hemophilia A (ICD-9-CM 286.0) receiving treatment with a clotting factor were eligible if they 1) were ≥18 years of age 2) did not receive Factor IX therapy and 3) did not have a diagnosis of Von Willebrand while receiving factor VIII therapy containing von Willebrand factor. All patient level resource utilization was converted to utilization per patient year. Resource utilization was then compared across time periods using repeated measures analysis of variance (ANOVA). The annualized number of haemophilia related events (haemophilic arthropathy or other joint related events) was calculated for each year. McNemar’s chi-square test was used to compare the frequencies across years.

Summary:

136 patients contributing 375 patient-years were included in this study. Office/clinic visits accounted for the majority of healthcare encounters annually; 7.5 all-cause visits per year and 2.2 haemophilia related visits per year. The number of annual all-cause office/clinic visits for Haemophilia A patients decreased significantly over time from 12.5 visits in 2008 to 5.9 visits in 2012 (p=0.0404), while haemophilia A-specific annual visits decreased from 4.0 to 1.5 (p=0.1991) during the same period. On average haemophilia A patients had less than 1 inpatient and emergency room visits per year, which did not change significantly over time (p=0.6371 and p=0.4845, respectively). Over the 5-year period, haemophilic events occurred in 30.93% of patient years, changed from 23.81% in 2009 to 34.09% in 2011 (p=0.6658).

Conclusions:

Office/clinic outpatient visits among patients diagnosed with haemophilia A has decreased overtime. However, the rate of haemophilia related arthropathies and other associated events have remained high. Further analysis is needed to understand how to best manage patients diagnosed with haemophilia A and reduce the proportion of patients who develop reduced joint mobility due to bleeding into joints.

Objectives:

Factor VIII (FVIII) prophylaxis regimens for severe hemophilia A that allow more flexible dosing than the standard 3-times-weekly regimen while maintaining efficacy may improve adherence. This analysis compared the clinical efficacy of once- or twice-weekly versus ≥3-times-weekly prophylaxis dosing of Bayer’s sucrose-formulated recombinant FVIII (rFVIII-FS) in patients with severe hemophilia A.

Methods:

Data from 3 postmarketing studies were pooled. Patients with severe hemophilia A and no history of inhibitors who were receiving ≥1 prophylaxis infusion/wk of rFVIII-FS for ≥80% of a prophylaxis observation period (≥5 months) were included. Patients were categorized based on age (<18 and ≥18 years) and physician-assigned treatment regimens of 1–2 prophylaxis injections/wk (n=63) or ≥3 prophylaxis injections/wk (n=76). Descriptive statistics were determined for annualized bleeding rates (ABRs) by dosing group and age subgroups.

Summary:

Median (quartile 1; quartile 3) ABR for all bleeds was 2.0 (0; 4.0) in the group receiving 1–2 prophylaxis injections/wk and 3.9 (1.5; 9.3) in the group with ≥3 prophylaxis injections/wk. Similarly, median ABRs for joint, spontaneous, and trauma-related bleeds were numerically lower in the group receiving 1–2 prophylaxis injections/wk. The trend toward lower ABRs in the group with 1–2 prophylaxis injections/wk was observed in both age subgroups, although ABRs were somewhat higher in patients ≥18 vs <18 years. Zero annualized bleeds were reported by 30% and 7% of patients in the groups with 1–2 prophylaxis injections/wk and ≥3 prophylaxis injections/wk, respectively.

Conclusions:

These data demonstrate that bleeding control can be achieved in some patients with severe hemophilia A using a <3-times-weekly prophylaxis dosing regimen and that physicians’ judgment based on bleeding phenotype can successfully direct the frequency of prophylactic dosing.

Objectives:

To determine the relationship between von Willebrand disease (vWD), dental plaque, and gingival bleeding in women with vWD and to determine the oral hygiene habits and dental care utilization in women with vWD.

Methods:

Consenting adult women with vWD (n=40) will have been recruited for this study. A questionnaire was given with 34 items covering topics such as dental care utilization, oral health quality of life, and oral hygiene habits. A brief oral examination was performed on each subject to assess which surfaces of the six Ramfjord teeth presented with dental plaque, and which surfaces bled upon flossing. Information was also gathered about each subject’s medical history, including the type of vWD, severity, and last von Willebrand factor levels.

Summary:

Data is still being collected for this study. Data collection will be completed on June 30. The data gathered so far shows that the majority of women who participated in this study have a high plaque score, yet minimal bleeding with flossing, when a gentle c-wrap flossing technique was performed.

Conclusions:

Results of this study are expected to show that the bleeding disorder has minimal effect on the amount of gingival bleeding that occurs with a c-wrap flossing technique. It’s possible that conclusions may be made that correct flossing technique can be performed in a manner that does not, in itself, cause gingival bleeding. This can perhaps assist in increasing the amount of people with bleeding disorders that floss, diminishing the fear that many people with bleeding disorders have of causing excessive bleeding with flossing.

Objective:

To evaluate the impact of interventions in a focused home infusion/specialty pharmacy based inhibitor management program on patient outcomes including, adherence, retention, prescriber communication.

Methods:

From our bleeding disorders patients’ databases between April 1, 2013 and March 31, 2014 (12 month period), prescriptions and assessment records were analyzed for patients with hemophilia A or B with inhibitors and those with acquired inhibitors. 49 unique patient records were reviewed, care managers were interviewed, and interventions were highlighted.

Results:

44 patients had Hemophilia A with an inhibitor, 2 had an inhibitor to Hemophilia B and 3 had acquired hemophilia. Hemophilia A patients had a diagnosis of severe hemophilia A (39), Moderate (2), Mild (2). 1 Hemophilia B patient was severe and the other moderate. Total number of active inhibitor patients on service (with a detectable Bethesda Unit titre) increased from 22 to 30 over this same period. 8 patients left service during the year due to insurance changes (4), and transfer to HTC’s 340B program (4). At the beginning of the study period, a multidisciplinary inhibitor management team (HTC experienced RN’s, RPh, SW, PT, Patient Advocate, and Hispanic Coordinator) was assembled and goals and processes for patient review and intervention were established. Monthly and ad hoc patient review meetings were implemented. Multiple barriers to adherence were encountered including immigration issues, language barriers, transportation issues, potential for caregiver burnout, storage and security of product concerns, relocations, product allergies, and needle phobia. Team worked collaboratively with HTC and other prescribers to intervene successfully in these issues. Interventions included long term twice daily nursing, securing an immigration attorney, hemophilia experienced translators, social worker, and physical therapist interventions, links to foundations for financial support, product bridge for insurance lapses, lab monitoring and reporting to HTC for remote patients, obtaining equipment (locking refrigerator) and protective supplies/ cooling compression cuffs. 30 patients received immune tolerance therapy during the study period. Of these, 25 were treated by an HTC and 5 were not. 10 patients on ITI achieved an “undetectable” inhibitor status during the study period. 8 were followed by an HTC and 2 were not. No patients were lost to therapy/management. All patients maintained positive interactions with prescribers and follow up visits.

Conclusion:

Inhibitor patients can be very challenging to manage. A focused, multidisciplinary inhibitor management team can extend the comprehensive model to the home, promote patient/prescriber/treatment team collaboration, and target interventions that enhance outcomes.

Objective:

Patient-centered medical home (PCMH), a team-based model of practice involving patients, families, providers and care team members, focuses on high quality, efficient, and patient-centered care. The purpose of this project was to implement appropriate elements of the PCMH model in the care delivered by the Intermountain Hemophilia and Thrombosis Center (IHTC).

Methods:

The IHTC, as a medical home neighbor, participated in a 3 1⁄2 year (5/2011- 11/2014) Children’s Health Improvement Collaborative Medical Home Demonstration (MHD) that involved 3 specialty and 9 primary care practices in Utah. IHTC focused on both MHD- wide and practice-specific quality improvement (QI) goals. Our QI team included the IHTC core multidisciplinary team and a parent partner and medical home coordinator (MHC) who were funded by the MHD. The MHD led four sequential, 8-12 month projects: “Improving Collaboration Among Pediatric Generalists and Specialists,” “Implementing Care and Self- Care Plans for Children with Chronic Conditions,” “Improving Healthcare Transitions for Children with Special Health Care Needs,” and “Sustainability.” Practice-specific projects targeted goals established via a needs assessment and parent partner input. Plan-Do-Study- Act (PDSA) cycles were facilitated by the MHC and a practice coach from the MHD. Continuing education and peer support were provided via learning sessions, webinars, and ongoing mentorship.

Summary:

IHTC met all MHD-wide and practice-specific goals. Selected MHD-wide improvements included: completion of the patient history prior to new consultation (improved from ~15% to 95%); patient self-care plans (0% to 97%); and youth with an up-to-date transition tool (0% to 100%). To address “sustainability,” IHTC will continue using QI, implementing the PCMH model, and will maintain the MHC as a member of the care team. Practice-specific strategies resulted in improved efficiency and family-centered approach to the annual comprehensive clinic visit (31⁄2 hour visit decreased to 2 hours with reduced redundancy), reduced no-show/cancellations (~33% to 10%), established means for continuous individual patient/family feedback, and a formalized IHTC-specific emergency preparedness plan (currently in progress).

Conclusions:

Via participation in the MHD, the IHTC learned that QI is both realistic and rewarding. Essential components for ongoing improvement include: specific, defined and measurable goals; a QI leader; parent/consumer input; and participation by all clinical team members. The PCMH model provides a framework for meaningful change for patients, families, and clinical practice.

Acknowledgments: 

Funded in part by a CHIPRA Quality Demonstrations grant: CFDA 93.767 from the U.S. Department of Health and Human Services, Centers for Medicare & Medicaid Services.

Introduction and Objective:

Prospective clinical trials have demonstrated the efficacy of prophylaxis in reducing bleeding episodes in hemophilia A and B patients and those with inhibitors. However, data, predominantly from observational studies, have suggested more equivocal effects on health-related quality of life (HRQoL) [Buchbinder 2013]. The present review examined the impact of prophylaxis on HRQoL as measured during prospective trials.

Methods:

We conducted a systematic literature review of prospective studies evaluating the efficacy of prophylaxis in hemophilia using factor VIII, factor IX, or bypassing agents. Applying the inclusion criteria, we selected studies which evaluated HRQoL via validated instruments and summarized key data.

Results:

A total of 12 studies (hemophilia A [n=7]; hemophilia B [n=2]; inhibitors [n=3]) met all inclusion criteria and were reviewed. Of these studies, the investigational products were Advate (n=2), Kogenate (n=2), NovoEight (n=2), Eloctate (n=1), Rixubis (n=1), Aprolix (n=1), Feiba (n=2), and NovoSeven (n=1). HRQoL was assessed using one or a combination of the following instruments: SF-36 (n=3), EQ-5D (n=5), Haemo-QoL (n=2), Haem-A-QoL (n=3), Haemo-QOL-A (n=2) and general pain VAS (n=1). Seven of the 12 studies reported significant improvement in ≥1 HRQoL measure following prophylaxis. Advate, Rixubis and Feiba prophylaxis (among good responders with ≥ 50% bleed reduction) demonstrated statistically significant and clinically meaningful improvement in the physical component and certain domain(s) scores of the SF-36 (Valentino 2012; Windyga 2013; Gringeri 2013). Additionally, prophylaxis with Feiba showed clinically meaningful and/or statistically significant improvements in HRQoL (EQ-5D, Haemo-A-QoL), general health status (EQ-VAS) and general pain scores (VAS) (Antunes 2014; Stasyshyn 2014). Although, a previous Kogenate study indicated non-significant change in HRQoL measures (Collins 2003), recently published results from the SPINART trial demonstrated statistically significant and clinically meaningful improvement in several domains of the Haemo-QoL-A (Hong 2014). Prophylaxis with Eloctate and Alprolix resulted in non-significant change in the HRQoL measures used in their respective trials (Wyrwich 2013). Statistical and clinical significance were not reported for prophylaxis treatment with NovoEight (Santagostino 2014). Prophylaxis with NovoSeven showed a non-significant trend towards improvement in all dimensions of the EQ-5D but statistical improvement in general health status (EQ-VAS) (Hoots 2008).

Conclusion:

Results from Advate, Kogenate, Rixubis and Feiba trials offer robust evidence of clinically and statistically significant improvement in HRQoL in hemophilia patients treated with prophylaxis.

Introduction and Objective:

Limited information exists in the recent literature capturing real- world utilization and cost of bypassing agents among hemophiliac patients with inhibitors in the US. The present study compared the cost of on-demand and prophylaxis treatment between aPCC and rFVIIa among inhibitor patients with severe hemophilia.

Methods:

A retrospective analysis of two large US specialty pharmacy databases was conducted using dispensing data over a 28-month period (Jan. 2012 to April 2014). Subjects were included if they had a diagnosis of hemophilia A or B (ICD-9 code 286.0 or 286.1) that was classified as severe and ≥12 months of consecutive prescription claims for only bypassing agents. For patients who switched between bypassing agents or between on- demand (OD) and prophylaxis (P) during the observation period, observations of ≥6 months with consistent prescriptions were selected and analyzed independently. Bypassing agent utilization was annualized and normalized by patient weight (kg). Cost was calculated using 2013 Redbook® US wholesale acquisition costs (aPCC=$1.81/U and rFVIIa=$1.77/μg) and compared by product and regimen using non-parametric statistics.

Results:

A total of 78 subjects with 84 observations met the inclusion criteria. Median age was 20 years old (range 2-64) and median time between the first and last prescription filled was 20.5 months. Approximately 34.5% of the subjects were on aPCC (44.8% [OD] and 55.2% [P]) and 40.5% were on rFVIIa (85.3% [OD] and 14.7% [P]). The remaining subjects (25%) were on various combinations of aPCC and rFVIIa. Median annualized utilization for aPCC and rFVIIa was 7,183U/kg (2,186U/kg [OD] and 9,612U/kg [P]) and 13,838μg/kg (9,493μg/kg [OD] and 27,245μg/kg [P]), respectively. Median annualized cost/kg was significantly lower (p=0.0071) among patients treated on-demand with aPCC ($3,956/kg) compared to rFVIIa ($16,801/kg). Similarly, median annualized cost/kg was also significantly lower (p=0.0093) among patients treated prophylactically with aPCC ($17,399/kg) compared to rFVIIa ($48,223/kg). Overall, median annualized cost/kg for on-demand and prophylaxis treatments was 76.5% and 63.9% lower, respectively, with aPCC compared to rFVIIa. Furthermore, there was no significant difference (p=0.6438) in median annualized cost/kg between aPCC prophylaxis and rFVIIa on-demand.

Conclusion:

Overall, these data suggest that the annualized treatment cost with aPCC is significantly lower compared to that of rFVIIa for both on-demand and prophylaxis regimens. For each patient treated on-demand or prophylactically with rFVIIa, approximately 3-4 patients could be treated with aPCC at comparable cost. Additionally, the median rFVIIa on- demand patient could be prescribed aPCC prophylactically to reduce bleeding episodes without significant cost implications.