When the regression analysis was repeated with the rest of the 63% of respondents, results were like the main analysis reported in Desk 1, with around intercept of 0.801, increment of +0.1091 for subcutaneous treatment, and decrement per bleed of ?0.0025. for subcutaneous vs infusion-based amount and therapies of bleeds; as well as for prophylactic regimens, an analysis of utilities by frequency of injections or infusions. Outcomes TTO interviews had been executed with 82 respondents. Mean resources [95% CI] had been highest for subcutaneous prophylaxis (0.90 [0.87C0.93]), followed by intravenous prophylaxis (0.81 [0.78C0.85]), and on-demand treatment (0.70 [0.65C0.76]). In regression analysis, subcutaneous treatment health states were associated with a utility increment of +0.1112. Additional bleeds and more frequent infusions were associated with lower utility values (?0.0027 per bleed and ?0.0003 per infusion). Conclusion Subcutaneous prophylaxis is associated with higher utility values compared to intravenous prophylactic and on-demand treatment, while increased bleeds and infusions are associated with reduced utility. strong class=”kwd-title” Keywords: Canadian societal perspective, health-related quality-of-life, utilities, hemophilia A Background Hemophilia is a rare congenital disorder that affects predominantly males, and is caused by a mutation of clotting factor genes on the X chromosome (X-linked) that result in a deficiency of factor VIII (FVIII) or -IX (FIX) in hemophilia A or B, respectively.1,2 Globally, 173,711 patients with hemophilia A were identified in 2018, and 3,018 were from Canada.1,3 Bleeding is the main symptom of hemophilia and it occurs after trauma or surgery (including minor/trivial injury), with the severity correlated with the degree of clotting factor deficiency.1,2 Bleeding can occur in muscles, Coumarin 7 joints, or soft tissue, and in life-threatening cases in the neck, throat, chest, gastrointestinal system, or intracranially.1,2 The main treatment goal is to prevent or treat bleeding; treatment of bleeds is generally via on-demand administration of specific factor concentrate to compensate for the deficient clotting factor, and historically prevention has included prophylaxis regimens of these factor-replacement therapies,1,2 with non-replacement factors having more recently become available.4 Other treatment goals are to prevent joint and muscle damage, prevent inhibitor development, prevent transmission of infections from blood products, and improve health-related quality-of-life (HRQoL).1,2 Until recently, prophylactic and on-demand treatments have consisted of intravenous exogenous FVIII replacement therapy with recombinant FVIII products or plasma-derived FVIII concentrates.1,2 Historically, hemophilia was primarily treated only when bleeding occurred (on-demand); however, over time the treatment paradigm shifted to prophylaxis with evidence that joint function is better preserved in patients with FVIII levels above 1% ( 1 IU/dL)1,2 Based on high quality evidence of the superiority of prophylactic treatment over on-demand treatment, it has become standard of care in Canada for patients with severe hemophilia.1,2 Short-acting exogenous FVIII (eg, Elocta) have a short half-life (8C12 hours), and patients require three-to-four prophylactic infusions each week to maintain adequate trough levels.1,5,6 Extended half-life (EHL), or long-acting FVIII (eg, Advate; 40% increase in half-life) are also available in Canada, which lessen the frequency of infusions, but still require multiple infusions per week.7 Although exogenous FVIII concentrate is an effective treatment, one possible serious complication is the development of FVIII inhibitors.1,2 Inhibitors are immunoglobulin G antibodies that inactivate both exogenous and endogenous FVIII, making FVIII replacement treatment ineffective, at high titers.1,2,6 Approximately 5C10% of patients with mild-to-moderate hemophilia A, and 20C30% of patients with severe hemophilia A, develop inhibitors.1,2 Emicizumab is a monoclonal antibody that restores the natural function of activated FVIII by bridging activated factor IX and factor X in hemophilia A patients to allow for effective hemostasis.1,5,8,9 Emicizumab, administered subcutaneously, has been shown to be effective in reducing bleeding events in patients with hemophilia A with inhibitors in the HAVEN 1 and 2 trials,10,11 as well as in patients with hemophilia A without inhibitors in the HAVEN 3 and 4 trials.1,5,12 Across the clinical trial program, clinical benefits of emicizumab have been observed for weekly, once every 2 weeks (Q2W), and once every 4 weeks (Q4W) dosing schedules (with Q4W dosing recommended only for adults and/or adolescents 40 kg [in the Canadian label]).13 The HRQoL of patients with hemophilia is negatively affected by both the disease and treatment.14 Recurrent Coumarin 7 bleeding and resulting complications such as joint and muscle damage, and pain and disability, can significantly affect patients HRQoL.14 Treatment-related factors include the need for frequent infusions due to the half-life of available therapies, and specific infusion-related problems such as difficulty with accessing veins, the time required to administer treatment, and development of inhibitors C all of which can have a negative effect on treatment adherence, lifestyle, and HRQoL.15 In addition to hemophilia patients,.For health state E, the regression-predicted utility was 0.903. experience, clinical trial results regarding bleed frequency, and validated by qualitative interviews of hemophilia patients and caregivers (n=10). Utilities were estimated via an online, trained interviewer-guided, vignette-based TTO exercise, where respondents valuated health states describing hemophilia patients (adults or children) receiving subcutaneous prophylaxis, intravenous prophylaxis, and on-demand treatments. Analyses included a descriptive analysis by health state; a mixed-effects analysis of utility values adjusted for subcutaneous vs infusion-based therapies and number of bleeds; and for prophylactic regimens, an analysis of utilities by frequency of infusions or injections. Results TTO interviews were conducted with 82 respondents. Mean utilities [95% CI] were highest for subcutaneous prophylaxis (0.90 [0.87C0.93]), followed by intravenous prophylaxis (0.81 [0.78C0.85]), and on-demand treatment (0.70 [0.65C0.76]). In regression analysis, subcutaneous treatment health states were associated with a utility increment of +0.1112. Additional bleeds and more frequent infusions were associated with lower utility values (?0.0027 per bleed and ?0.0003 per infusion). Conclusion Subcutaneous prophylaxis is associated with higher utility values compared to intravenous prophylactic and on-demand treatment, while increased bleeds and infusions Coumarin 7 are associated with reduced utility. strong class=”kwd-title” Keywords: Canadian societal perspective, health-related quality-of-life, utilities, hemophilia A Background Hemophilia is a rare congenital disorder that affects predominantly males, and is caused by a mutation of clotting factor genes on the X chromosome (X-linked) that result in a deficiency of factor VIII Coumarin 7 (FVIII) or -IX (FIX) in hemophilia A or B, respectively.1,2 Globally, 173,711 patients with hemophilia A were identified in 2018, and 3,018 were from Canada.1,3 Bleeding is the main symptom of hemophilia and it occurs after trauma or surgery (including minor/trivial injury), with the severity correlated with the degree of clotting factor deficiency.1,2 Bleeding can occur in muscles, joints, or soft tissue, and in life-threatening cases in the neck, throat, chest, gastrointestinal system, or intracranially.1,2 The main treatment goal is to prevent or treat bleeding; treatment of bleeds is generally via on-demand administration of specific factor concentrate to compensate for the deficient clotting factor, and historically prevention has included prophylaxis regimens of these factor-replacement therapies,1,2 with non-replacement factors having more recently become available.4 Other treatment goals are to prevent joint and muscle damage, prevent inhibitor development, prevent transmission of infections from blood products, and improve health-related quality-of-life (HRQoL).1,2 Until recently, prophylactic and on-demand treatments have consisted of intravenous exogenous FVIII replacement therapy with recombinant FVIII products or plasma-derived FVIII concentrates.1,2 Historically, hemophilia was primarily treated only when bleeding occurred (on-demand); however, over time the treatment paradigm shifted to prophylaxis with evidence that joint function is better preserved in patients with FVIII levels above 1% ( 1 IU/dL)1,2 Based on high quality evidence of the superiority of prophylactic treatment over on-demand treatment, it has become standard of care in Canada for patients with severe hemophilia.1,2 Short-acting exogenous FVIII (eg, Elocta) have a short half-life (8C12 hours), and patients require three-to-four prophylactic infusions each week to maintain adequate trough levels.1,5,6 Extended half-life (EHL), or long-acting FVIII (eg, Advate; 40% increase in half-life) are also available in Canada, which lessen the frequency of infusions, but still require multiple infusions per week.7 Although exogenous FVIII concentrate is an effective treatment, one possible serious complication is the development of FVIII inhibitors.1,2 Inhibitors are immunoglobulin G antibodies that inactivate both exogenous and endogenous FVIII, making FVIII replacement treatment ineffective, at high titers.1,2,6 Approximately 5C10% of patients with mild-to-moderate hemophilia A, and 20C30% of patients with severe hemophilia A, develop inhibitors.1,2 Emicizumab is a monoclonal antibody that restores the natural function of activated FVIII by bridging activated factor IX and factor X in hemophilia A patients to allow for effective hemostasis.1,5,8,9 Emicizumab, administered subcutaneously, has been shown to be effective in reducing bleeding events in patients with hemophilia A with inhibitors in the HAVEN 1 and 2 trials,10,11 aswell such Rabbit Polyclonal to CDK10 as patients with hemophilia A without inhibitors in the HAVEN 3 and 4 trials.1,5,12 Over the clinical trial plan, clinical great things about emicizumab have already been observed for regular, once every 14 days (Q2W), as soon as every four weeks (Q4W) dosing schedules (with Q4W dosing recommended limited to adults and/or children 40 kg Coumarin 7 [in the Canadian label]).13 The HRQoL of sufferers with hemophilia is negatively suffering from both disease and treatment.14 Recurrent bleeding and causing complications such as for example joint.