Observational Study of Real-World Factor Utilization and Health Outcomes in Patients with Hemophilia in Canada
Authors: Sun Haowei Linda , Yang Ming , Poon Man-Chiu , Lee Adrienne , Robinson Katherine Sue , Sholzberg Michelle , Wu John K. , Iorio Alfonso , Blanchette Victor S. , Klaassen Robert J , Jackson Shannon 
Published: October 2019

Abstract
Introduction: Recombinant Factors VIII Fc (rFVIIIFc) and IX Fc (rFIXFc) fusion proteins are extended half-life (EHL) factor products approved in Canada in 2014 and became available through the Canadian Blood Services in January 2016. Real-world product utilization and clinician practice patterns in EHL prescription are unknown.
Objectives: This is a prospective Canadian multi-centre observational study to describe product utilization, clinical and patient-reported outcomes (PROs) in patients pre- and post-switch to rFVIIIFc/ rFIXFc products compared to those who remained on standard half-life (SHL) products. The primary outcome is intra-individual change in annualized factor consumption from 12-month period pre-switch to 24-month post-switch to rFVIIIFc/rFIXFc. This analysis describes the baseline clinical characteristics and intra-individual changes in PROs from the cohort who completed baseline, 3-month and 12-month assessment before June 2018 in this ongoing study.
Methods: Males aged ≥12 years with moderate and severe hemophilia A and B (factor level <5%) with no active inhibitors across 10 Canadian sites were enrolled; whether they were treated with prophylaxis or on-demand. Factor utilization, bleeding events, treatment regimen, and PROs were collected at baseline, 3-month, 1-year and 2-years. PRO tools evaluated in this analysis include hemophilia specific health related quality of life (HRQoL) measured with the Haemophilia Quality of Life Questionnaire for Adults (Haem-A-QoL) in adults and the Canadian Hemophilia Outcomes-Kid's Life Assessment Tool (CHO-KLAT) in adolescents. Haem-A-QoL scales range from 0-100, with lower scores reflecting better HRQoL, whereas higher scores in CHO-KLAT reflect better HRQoL. Treatment satisfaction was measured using the Treatment Satisfaction Questionnaire for Medication (TSQM-9), and chronic pain was measured using numeric rating scale from 0-10 (visual analog scale in adolescents).
Results: Forty-one patients were included in this interim analysis, 29 with hemophilia A (on-demand n=4) and 12 with hemophilia B (on-demand n=2). Median age was 30 years (range 13-67). Six patients (15%) had target joints within 6 months prior to enrollment. Twenty patients remained on SHL products, 13 were switched to rFVIIIFc (2 from on-demand to once weekly prophylaxis) and 8 to rFIXFc. Common dosing regimens were: rFVIIIFc 50-65 units/kg once weekly (n=6), 20-40 units/kg twice weekly or every 3 days (n=5), and rFIXFc 40-60 units/kg once weekly (n=5). Patients who switched to Fc products tended to be older, have more severe hemophilic arthropathy, higher intensity of chronic pain related to hemophilia, and worse HRQoL than those who remained on SHL products (Table 1). The most common reasons for switching to EHL were: less infusions/ convenience (n=10), patient preference (n=9), quality of life (n=8), difficulty adhering to prophylaxis with SHL (n=7). The most common reasons for staying on SHL were: doing well on current regimen (n=18), not meeting criteria for EHL (n=8), familiarity with SHL (n=6). The rationale for EHL dose/dosing frequency is largely driven by "fixed regimen to promote adherence" (n=11) and "longer interval for convenience" (n=6), only 6 patients were dosed "for a higher trough than previous regimen".
Among rFVIII to rFVIIIFc switchers and rFIX to rFIXFc switchers, there were no significant changes in the total Haem-A-QoL scores from baseline to 3-month and from baseline to 12-month (paired Wilcoxon signed-rank test, Table 2). The median paired differences in the Haem-A-QoL total score did not meet the clinically meaningful difference threshold in any groups. Similarly, there were no significant intra-individual changes in the CHO-KLAT score, chronic pain intensity, and TSQM-9 score from baseline to 3-month and 12-month after switch.
Conclusion: We found that a cohort of Canadian patients with moderate-severe hemophilia appear to be switched to rFVIIIFc/ rFIXFc on the basis of patient convenience, expected improvement in HRQoL, and prophylaxis adherence. Although limited by a small sample size, there appears to be no significant within-individual changes in hemophilia specific HRQoL, chronic pain, and treatment satisfaction. Data collection is ongoing (expected completion date September 2019) to provide additional insight on various clinical and patient reported outcomes in the larger study population.

Disclosures
Sun: Novo Nordisk: Honoraria; Octapharma: Research Funding. Poon:Novo Nordisk: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Research Funding; Bayer: Research Funding, Speakers Bureau; Octapharma: Consultancy; Pfizer: Consultancy, Speakers Bureau; Roche: Consultancy; Biogen: Consultancy; Baxalta/ Shire: Consultancy. Lee:Bayer: Other: Project based funding from Bayer Hemophilia Awards Program; Bioverativ: Research Funding. Robinson:Roche: Honoraria, Other: Advisory board, Research Funding, Speakers Bureau; Celgene: Other: Advisory board, Speakers Bureau. Wu:Bayer: Honoraria, Other: Advisory board, Research Funding; Shire: Honoraria; Pfizer: Other: Advisory board; Bioverativ: Honoraria, Other: Advisory board; Novo Nordisk: Honoraria, Other: Advisory board; Octapharma: Honoraria, Other: Advisory board; CSL Behring: Honoraria, Other: Advisory board. Iorio:CSL: Other: Alfonso Iorio's Institution has received project based funding via research or service agreements with CSL; Bayer: Other: Alfonso Iorio's Institution has received project based funding via research or service agreements with Bayer; Grifols: Other: Alfonso Iorio's Institution has received project based funding via research or service agreements with Grifols; Pfizer: Other: Alfonso Iorio's Institution has received project based funding via research or service agreements with Pfizer; Roche: Other: Alfonso Iorio's Institution has received project based funding via research or service agreements with Roche; Octapharma: Other: Alfonso Iorio's Institution has received project based funding via research or service agreements with Octapharma; NovoNordisk: Other: Alfonso Iorio's Institution has received project based funding via research or service agreements with Novo Nordisk; Shire: Other: Alfonso Iorio's Institution has received project based funding via research or service agreements with Shire. Blanchette:Bioverativ: Other: Investigator-initiated research funding; Bayer: Other: speaker's fees; Novo Nordisk: Other: Speaker's fees; Pfizer: Other: Speaker's fees; Shire: Other: Speaker's fees; Shire: Other: Investigator-initiated research funding. Klaassen:Hoffman-La Roche: Consultancy; Shire: Consultancy; Agios Pharmaceuticals Inc.: Consultancy; Amgen Inc.: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding; Octapharma AG: Consultancy, Honoraria; Cangene: Research Funding. Jackson:Bayer: Honoraria; Novo Nordisk: Honoraria; Shire: Honoraria; Bioverativ: Other: Investigator initiated grant funding; Roche: Honoraria; Pfizer: Honoraria.