Treatment Patterns And Outcomes In Patients Treated With Benefix Or Refacto/Refacto AF - A Swedish Cohort Study

Study Overview
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Brief Summary
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The overall aim of the study is to describe demographic and clinical characteristics, treatment patterns and outcomes, in the populations of hemophilia patients treated with BeneFIX and ReFacto/ReFacto AF in Sweden

Detailed Description
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The overall aim of the study is to describe demographic and clinical characteristics, treatment patterns and outcomes, as well as the related direct treatment costs in the populations of hemophilia patients treated with BeneFIX and ReFacto/ReFacto AF, and in subgroups (e.g. level of severity) at the MHC in Sweden. The study population will consist of all patients diagnosed with haemophilia (D66.9 (haemophilia A) D67.9 (haemophilia B) in International Statistical Classification of Diseases and Related Health Problems (ICD-10) that have been registered in the MHR since 1977 and that have had at least one registered prescription of BeneFIX or ReFacto/ReFacto AF in the MHR since market authorization of the respective product (Benefix August 27 1997, ReFacto April 13 1999, ReFacto AF July 1 2009). Diseased individuals are included. Information on drugs picked up at the pharmacy is available in the Prescribed Drug Register from 2005.

Official Title
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TREATMENT PATTERNS AND OUTCOMES IN PATIENTS TREATED WITH BENEFIX OR REFACTO/REFACTO AF - A SWEDISH COHORT STUDY

Conditions
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Hemophilia A, Hemophilia B

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The study population will consist of all patients diagnosed with hemophilia (D66.9 (hemophilia A) D67.9 (hemophilia B) in International Statistical Classification of Diseases and Related Health Problems (ICD-10) that have been registered in the Malmö Hemophilia Register since 1977 and that have had at least one registered prescription of BeneFIX or ReFacto/ReFacto AF in the MHR since market authorization of the respective product Exclusion Criteria: No exclusion criteria in this study

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with Haemophilia A<br>Patients in The MHR diagnosed with Haemophilia A | |
| Patients with Haemophilia B<br>Patients in The MHR diagnosed with Haemophilia B | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Age of Participants at Disease Diagnosis |  | At disease diagnosis within 11 years before the study start date (Day 1) | 
| Age of Participants at Start of Treatment With Benefix or Refacto |  | At start of treatment with Benefix/Refacto within 11 years before the study start date (Day 1) | 
| Age of Participants at Start of Replacement Treatment | Participants diagnosed with coagulation disorders received intravenous replacement treatment of the missing coagulation factor. Replacement treatment could be given prophylactically or to stop the bleed and/or to stop it from becoming more severe. | At start of replacement treatment within 11 years before the study start date (Day 1) | 
| Average Prescribed Dose Per Infusion for Factor VIII and Factor IX Concentrates | Participants diagnosed with coagulation disorders received intravenous replacement treatment of the missing coagulation factor (Factor VIII or IX). Data was measured in international units (IU) for factor VIII and factor IX concentrates. | For the duration of 11 years before the study start date (Day 1) | 
| Average Prescribed Dose Per Kilogram Bodyweight for Factor VIII and Factor IX Concentrates | The average dose per kilogram body weight of factor VIII and IX was defined as a set of two derived variables from the MHR based on information on prescribed replacement treatment (Benefix or Refacto/Refacto AF): prescribed dose per infusion divided by registered body weight (all participants) and prescribed dose per week (prescribed dose per infusion multiplied by registered number of infusions per week) divided by registered body weight (only participants on prophylaxis). | For the duration of 11 years before the study start date (Day 1) | 
| Percentage of Participants on Prophylactic Treatment | Prophylactic treatment was defined as administration of drug regularly to reduce the insufficiency of coagulation factor to prevent bleeding to occur. | For the duration of 11 years before the study start date (Day 1) | 
| Average Prescribed Frequency of Infusions Per Week Dispensed for Haemophilia A or B Participants With Prophylaxis |  | For the duration of 11 years before the study start date (Day 1) | 
| Average Prescribed Annual Dose of Factor VIII and IX Concentrates for Participants on Prophylaxis | Participants diagnosed with coagulation disorders received intravenous replacement treatment of the missing coagulation factor (Factor VIII or IX). Prescribed annual dose of factor concentrate was derived from the MHR registration of prescribed annual dose of factor concentrate. | For the duration of 11 years before the study start date (Day 1) | 
| Average Prescribed Annual Dose of Factor VIII and IX Concentrates Per Kilogram Bodyweight for Participants on Prophylaxis | Participants diagnosed with coagulation disorders received intravenous replacement treatment of the missing coagulation factor (Factor VIII or IX). Prescribed annual dose of factor concentrate per kilogram body weight was derived from the MHR registration of prescribed annual dose of factor concentrate and the registered body weight. | For the duration of 11 years before the study start date (Day 1) | 
| Average Annual Registered Consumption of Factor VIII and IX Concentrates | Participants diagnosed with coagulation disorders received intravenous replacement treatment of the missing coagulation factor (Factor VIII or IX). Average annual registered consumption of factor VIII and IX concentrates was defined as MHR registered participant's reports on factor concentrate consumption during calendar year. | For the duration of 11 years before the study start date (Day 1) | 
| Number of Participants With Consumption of Factor VIII, Factor IX, Factor rVIIa and/or aPCC Concentrate | Participants who develop inhibitors to factor VIII or IX concentrates were treated with bypassing agents in the form of activated prothrombin complex concentrate (aPCC) which was measured in units (U) and/or recombinant factor VIIa (rFVIIa) measured in micrograms (mcg). | For the duration of 11 years before the study start date (Day 1) | 
| Percentage of Time on Refacto or Benefix | Percentage of time (in days) on Refacto/Refacto AF or Benefix was calculated as total number of days when participant was prescribed Refacto/Refacto AF or Benefix over the total number of days on any replacement treatment. Total number of days on any replacement treatment was derived from date of start of replacement treatment according to MHR and August 31, 2015 or date of death, whichever was earliest. | For the duration of 11 years before the study start date (Day 1) | 
| Average Use of Factor Concentrate Per Surgery Event at Hospital for Invasive Procedures |  | For the duration of 11 years before the study start date (Day 1) | 
| Average Factor Concentrate Use at Hospital for Invasive Procedures | Average factor concentrate use was calculated as percentage of total annual use of factor concentrates (in IU) at hospital for invasive procedures. | For the duration of 11 years before the study start date (Day 1) | 
| Average Annual Number of Filled Prescriptions of Factor Concentrate | Data at end of every year was based on the number of filled prescriptions during the last 3 years. | For a duration of 3 years (for up to 11 years before the study start Day 1) | 
| Average Annual Number of Dispensed Units of Factor Concentrate | To assess annual consumption of factor concentrates, calculations were based on prescription date as start of use and the day before the next prescription as the last date of use of the factor concentrates retrieved. The annual number of dispensed units of factor concentrate were then summed up of all dispensed units of factor concentrate with periods within the calendar year plus estimates of average daily use periods extending over two years. Data at end of every year was based on the number of dispensed units of factor concentrate during the last 3 years. | For a duration of 3 years (for up to 11 years before the study start Day 1) | 
| Average Number of Units of Benefix or Refacto | Data from the National Board of Health and Welfare (NBHW) had information on all filled prescriptions from July 1, 2005-last date of observation (August 31, 2015). Derived variable calculated as total number of units of filled prescriptions of Refacto/Refacto AF and Benefix over the total units of all factor VIII concentrates and factor IX concentrates, respectively. Total number of units were derived from the date of start of NBHW to last available observation or date of death, whichever was earliest. | For the duration of 11 years before the study start date (Day 1) | 
| Total Number of Bleeds |  | For the duration of 11 years before the study start date (Day 1) | 
| Number of Joint Bleed, Muscle Bleeds and Other Bleed Events in Participants | Joint bleeds included traumatic and spontaneous joint bleeds, muscle bleeds included traumatic and spontaneous soft tissue bleeds and other bleed events included intracranial bleed, gastrointestinal bleed and urinary tract bleed. | For the duration of 11 years before the study start date (Day 1) | 
| Gilbert Joint Score | Gilbert joint score was an instrument to measure joint health in the domain of body structure and function (i.e. impairment), of the joints most commonly affected by bleeding in haemophilia - knees, ankles, elbows. Total score ranged from 0-100, evaluating ankle, knee and elbow, where 0 indicated normal joint function, 100 indicated worst joint function, where higher values indicated more impairment in joints. | Data analyzed on study start Day 1 for the duration of 4 years (2005 to 2009) | 
| Haemophilia Joint Health Score | Haemophilia Joint Health Score (HJHS) was used to assess joint damage in participants with haemophilia. Total score ranges from 0 to 124, where, 0 indicates normal function, and 124 indicates worst joint function, higher values indicated more damage in joints. | Data analyzed on study start Day 1 for the duration of 6 years (2009 to 2015) | 
| Percentage of Participants With Surgeries | Percentage of participants who had any type of surgery (arthrodesis, surgery on foot, nose, elbow, hand or shoulder, surgery on hip, surgery on knee, tooth extraction, venous port or any other) during the data observation period were reported. | For the duration of 11 years before the study start date (Day 1) | 
| Average Relative Dose Intensity of Factor Concentrate Dispensed for Haemophilia A or B Participants on Prophylaxis Based on Dispensed Volume of Units | Relative dose intensity based on dispensed volume of units was calculated using annual dispensed volume of factor concentrate per participant divided by annual prescribed dose per participant. Data was analysed for 2 categories separately: children/adolescents and adults. | For the duration of 11 years before the study start date (Day 1) | 
| Average Cost of Replacement Treatment (Benefix or Refacto/Refacto AF) Related to Bleed Event |  | For the duration of 11 years before the study start date (Day 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Annual Cost of Prescribed Factor Concentrate and Dispensed Replacement Treatment |  | For the duration of 11 years before the study start date (Day 1) | 
| Average Cost of Replacement Treatment Related to Invasive Procedures |  | For the duration of 11 years before the study start date (Day 1) |