Hemophilia A, Hemophilia B
Conditions
Brief summary
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
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.
Interventions
None listed
Sponsors
Pfizer
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | — |
| Gilbert Joint Score | Data analyzed on study start Day 1 for the duration of 4 years (2005 to 2009) | 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. |
| Haemophilia Joint Health Score | Data analyzed on study start Day 1 for the duration of 6 years (2009 to 2015) | 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. |
| Percentage of Participants With Surgeries | For the duration of 11 years before the study start date (Day 1) | 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. |
| Average Relative Dose Intensity of Factor Concentrate Dispensed for Haemophilia A or B Participants on Prophylaxis Based on Dispensed Volume of Units | For the duration of 11 years before the study start date (Day 1) | 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. |
| 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 | At start of replacement treatment within 11 years before the study start date (Day 1) | 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. |
| Average Prescribed Dose Per Infusion for Factor VIII and Factor IX Concentrates | For the duration of 11 years before the study start date (Day 1) | 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. |
| Average Prescribed Dose Per Kilogram Bodyweight for Factor VIII and Factor IX Concentrates | For the duration of 11 years before the study start date (Day 1) | 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). |
| Percentage of Participants on Prophylactic Treatment | For the duration of 11 years before the study start date (Day 1) | Prophylactic treatment was defined as administration of drug regularly to reduce the insufficiency of coagulation factor to prevent bleeding to occur. |
| 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 | For the duration of 11 years before the study start date (Day 1) | 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. |
| Average Prescribed Annual Dose of Factor VIII and IX Concentrates Per Kilogram Bodyweight for Participants on Prophylaxis | For the duration of 11 years before the study start date (Day 1) | 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. |
| Average Annual Registered Consumption of Factor VIII and IX Concentrates | For the duration of 11 years before the study start date (Day 1) | 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. |
| Number of Participants With Consumption of Factor VIII, Factor IX, Factor rVIIa and/or aPCC Concentrate | For the duration of 11 years before the study start date (Day 1) | 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). |
| Percentage of Time on Refacto or Benefix | For the duration of 11 years before the study start date (Day 1) | 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. |
| 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 | For the duration of 11 years before the study start date (Day 1) | Average factor concentrate use was calculated as percentage of total annual use of factor concentrates (in IU) at hospital for invasive procedures. |
| Average Annual Number of Filled Prescriptions of Factor Concentrate | For a duration of 3 years (for up to 11 years before the study start Day 1) | Data at end of every year was based on the number of filled prescriptions during the last 3 years. |
| Average Annual Number of Dispensed Units of Factor Concentrate | For a duration of 3 years (for up to 11 years before the study start Day 1) | 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. |
| Average Number of Units of Benefix or Refacto | For the duration of 11 years before the study start date (Day 1) | 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. |
| 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 | For the duration of 11 years before the study start date (Day 1) | 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. |
Secondary
| Measure | 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) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Average Cost for Replacement Treatment Related to Invasive Procedures | Data analyzed on study start Day 1 for Year 1 (2005) and Year 7 (2011) | The average cost for replacement treatment related to invasive procedures was derived from the percentage of total costs for dispensed replacement therapy and calculated as: cost of factor concentrate used for invasive procedures/ total cost of factor concentrate. |
| Average Annual Cost of Replacement Treatment Related to Invasive Procedures | Data analyzed on study start Day 1 for Year 1 (2005) and Year 7 (2011) | — |
Participant flow
Pre-assignment details
The study was a retrospective population-based register study. Detailed data on each participant diagnosed with haemophilia was retrieved from the Malmö Haemophilia Register (MHR) in January 2016 covering the period of January 2005 up to December 2015.
Participants by arm
| Arm | Count |
|---|---|
| Benefix/Refacto/Refacto AF Participants diagnosed with haemophilia A and B who were registered in the MHR and had at least one registered prescription of Benefix or Refacto/Refacto AF were included in the study and their data (for the duration of 11 years, i.e. 2005-2015) was retrospectively observed. | 86 |
| Total | 86 |
Baseline characteristics
| Characteristic | Benefix/Refacto/Refacto AF | — |
|---|---|---|
| Age, Continuous | 34 years STANDARD_DEVIATION 20.9 | — |
| Percentage of Participants Infected With Hepatitis C | 40 percentage of participants | — |
| Percentage of Participants Who Had Died During the Prior 11 Year Period | 0 percentage of participants | — |
| Percentage of Participants with Inhibitor Status Current | 2 percentage of participants | — |
| Percentage of Participants with Inhibitor Status Ever | 1 percentage of participants | — |
| Percentage of Participants with Inhibitor Status Never | 97 percentage of participants | — |
| Percentage of Participants With Positive Human Immunodeficiency Virus (HIV) status | 5 percentage of participants | — |
| Percentage of Participants With Severe, Moderate and Mild Haemophilia A or B Mild | 20 percentage of participants | — |
| Percentage of Participants With Severe, Moderate and Mild Haemophilia A or B Moderate | 24 percentage of participants | — |
| Percentage of Participants With Severe, Moderate and Mild Haemophilia A or B Severe | 56 percentage of participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 3 Participants | — |
| Sex: Female, Male Male | 83 Participants | — |
| Year of Birth for Participants | 1985 years | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 86 |
| other Total, other adverse events | 0 / 86 |
| serious Total, serious adverse events | 0 / 86 |
Outcome results
Primary
Age of Participants at Disease Diagnosis
Time frame: At disease diagnosis within 11 years before the study start date (Day 1)
Population: MHR Benefix or Refacto/Refacto AF analysis set: all participants diagnosed with haemophilia A or B in ICD-10, registered in MHR since 1977, had at least 1 registered prescription of Benefix or Refacto/Refacto AF in MHR since market authorization of respective product. Here, N= number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benefix/Refacto/Refacto AF: Haemophilia A | Age of Participants at Disease Diagnosis | 5 years | Standard Deviation 10.1 |
| Benefix/Refacto/Refacto AF: Haemophilia B | Age of Participants at Disease Diagnosis | 7 years | Standard Deviation 10.7 |
Primary
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.
Time frame: At start of replacement treatment within 11 years before the study start date (Day 1)
Population: MHR Benefix or Refacto/Refacto AF analysis set: all participants diagnosed with haemophilia A or B in ICD-10, registered in MHR since 1977, had at least 1 registered prescription of Benefix or Refacto/Refacto AF in MHR since market authorization of respective product.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benefix/Refacto/Refacto AF: Haemophilia A | Age of Participants at Start of Replacement Treatment | 16 years | Standard Deviation 15.6 |
| Benefix/Refacto/Refacto AF: Haemophilia B | Age of Participants at Start of Replacement Treatment | 27 years | Standard Deviation 20.3 |
Primary
Age of Participants at Start of Treatment With Benefix or Refacto
Time frame: At start of treatment with Benefix/Refacto within 11 years before the study start date (Day 1)
Population: MHR Benefix or Refacto/Refacto AF analysis set: all participants diagnosed with haemophilia A or B in ICD-10, registered in MHR since 1977, had at least 1 registered prescription of Benefix or Refacto/Refacto AF in MHR since market authorization of respective product. Here, N= number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benefix/Refacto/Refacto AF: Haemophilia A | Age of Participants at Start of Treatment With Benefix or Refacto | 18 years | Standard Deviation 16.2 |
| Benefix/Refacto/Refacto AF: Haemophilia B | Age of Participants at Start of Treatment With Benefix or Refacto | 30 years | Standard Deviation 20.9 |
Primary
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.
Time frame: For a duration of 3 years (for up to 11 years before the study start Day 1)
Population: MHR Benefix or Refacto/Refacto AF analysis set: all participants diagnosed with haemophilia A or B in ICD-10, registered in MHR since 1977, had at least 1 registered prescription of Benefix or Refacto/Refacto AF in MHR since market authorization of respective product. Here, n= number of participants with available data for each category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Annual Number of Dispensed Units of Factor Concentrate | Factor VIII (2005) | 109000 dispensed units | Standard Deviation 79000 |
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Annual Number of Dispensed Units of Factor Concentrate | Factor VIII (2008) | 219000 dispensed units | Standard Deviation 151000 |
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Annual Number of Dispensed Units of Factor Concentrate | Factor VIII (2011) | 220000 dispensed units | Standard Deviation 138000 |
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Annual Number of Dispensed Units of Factor Concentrate | Factor VIII (2014) | 235000 dispensed units | Standard Deviation 130000 |
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Annual Number of Dispensed Units of Factor Concentrate | Factor IX (2005) | 68000 dispensed units | Standard Deviation 71000 |
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Annual Number of Dispensed Units of Factor Concentrate | Factor IX (2008) | 163000 dispensed units | Standard Deviation 140000 |
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Annual Number of Dispensed Units of Factor Concentrate | Factor IX (2011) | 194000 dispensed units | Standard Deviation 217000 |
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Annual Number of Dispensed Units of Factor Concentrate | Factor IX (2014) | 212000 dispensed units | Standard Deviation 200000 |
Primary
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.
Time frame: For a duration of 3 years (for up to 11 years before the study start Day 1)
Population: MHR Benefix or Refacto/Refacto AF analysis set: all participants diagnosed with haemophilia A or B in ICD-10, registered in MHR since 1977, had at least 1 registered prescription of Benefix or Refacto/Refacto AF in MHR since market authorization of respective product. Here, n= number of participants with available data for each category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Annual Number of Filled Prescriptions of Factor Concentrate | 2005 | 5 prescriptions | Standard Deviation 4 |
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Annual Number of Filled Prescriptions of Factor Concentrate | 2008 | 11 prescriptions | Standard Deviation 8 |
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Annual Number of Filled Prescriptions of Factor Concentrate | 2011 | 11 prescriptions | Standard Deviation 7 |
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Annual Number of Filled Prescriptions of Factor Concentrate | 2014 | 11 prescriptions | Standard Deviation 7 |
Primary
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.
Time frame: For the duration of 11 years before the study start date (Day 1)
Population: MHR Benefix or Refacto/Refacto AF analysis set: all participants diagnosed with haemophilia A or B in ICD-10, registered in MHR since 1977, had at least 1 registered prescription of Benefix or Refacto/Refacto AF in MHR since market authorization of respective product. Here, N= number of participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Annual Registered Consumption of Factor VIII and IX Concentrates | Factor VIII | 80000 IU/year | Standard Deviation 70000 |
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Annual Registered Consumption of Factor VIII and IX Concentrates | Factor IX | 73000 IU/year | Standard Deviation 53000 |
Primary
Average Cost of Replacement Treatment (Benefix or Refacto/Refacto AF) Related to Bleed Event
Time frame: For the duration of 11 years before the study start date (Day 1)
Population: MHR Benefix or Refacto/Refacto AF analysis set: all participants diagnosed with haemophilia A or B in ICD-10, registered in MHR since 1977, had at least 1 registered prescription of Benefix or Refacto/Refacto AF in MHR since market authorization of respective product. Here, N= number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Cost of Replacement Treatment (Benefix or Refacto/Refacto AF) Related to Bleed Event | 100000 Swedish Krona (SEK) | Standard Deviation 121000 |
Primary
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.
Time frame: For the duration of 11 years before the study start date (Day 1)
Population: MHR Benefix or Refacto/Refacto AF analysis set: all participants diagnosed with haemophilia A or B in ICD-10, registered in MHR since 1977, had at least 1 registered prescription of Benefix or Refacto/Refacto AF in MHR since market authorization of respective product.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Factor Concentrate Use at Hospital for Invasive Procedures | 2 percentage of factor concentrate | Standard Deviation 14 |
Primary
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.
Time frame: For the duration of 11 years before the study start date (Day 1)
Population: MHR Benefix or Refacto/Refacto AF analysis set: all participants diagnosed with haemophilia A or B in ICD-10, registered in MHR since 1977, had at least 1 registered prescription of Benefix or Refacto/Refacto AF in MHR since market authorization of respective product. Here, n= number of participants with available data for each category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Number of Units of Benefix or Refacto | Refacto - Factor VIII | 229000 units | Standard Deviation 130000 |
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Number of Units of Benefix or Refacto | Benefix - Factor IX | 191000 units | Standard Deviation 163000 |
Primary
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.
Time frame: For the duration of 11 years before the study start date (Day 1)
Population: Analysis was performed on MHR Benefix or Refacto/Refacto AF analysis set. Here, overall number of participants analysed signifies participants who were evaluable for this outcome measure and number analysed signifies number of participants with available data for each category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Prescribed Annual Dose of Factor VIII and IX Concentrates for Participants on Prophylaxis | Factor IX | 367000 IU/year | Standard Deviation 187000 |
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Prescribed Annual Dose of Factor VIII and IX Concentrates for Participants on Prophylaxis | Factor VIII | 286000 IU/year | Standard Deviation 116000 |
Primary
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.
Time frame: For the duration of 11 years before the study start date (Day 1)
Population: Analysis was performed on MHR Benefix or Refacto/Refacto AF analysis set. Here, overall number of participants analysed signifies participants who were evaluable for this outcome measure and number analysed signifies number of participants with available data for each category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Prescribed Annual Dose of Factor VIII and IX Concentrates Per Kilogram Bodyweight for Participants on Prophylaxis | Factor VIII | 4500 IU/kg/year | Standard Deviation 800 |
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Prescribed Annual Dose of Factor VIII and IX Concentrates Per Kilogram Bodyweight for Participants on Prophylaxis | Factor IX | 4700 IU/kg/year | Standard Deviation 2200 |
Primary
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.
Time frame: For the duration of 11 years before the study start date (Day 1)
Population: MHR Benefix or Refacto/Refacto AF analysis set: all participants diagnosed with haemophilia A or B in ICD-10, registered in MHR since 1977, had at least 1 registered prescription of Benefix or Refacto/Refacto AF in MHR since market authorization of respective product. Here, n= number of participants with available data for each category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Prescribed Dose Per Infusion for Factor VIII and Factor IX Concentrates | Factor VIII | 1600 IU | Standard Deviation 700 |
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Prescribed Dose Per Infusion for Factor VIII and Factor IX Concentrates | Factor IX | 2500 IU | Standard Deviation 900 |
Primary
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).
Time frame: For the duration of 11 years before the study start date (Day 1)
Population: MHR Benefix or Refacto/Refacto AF analysis set: all participants diagnosed with haemophilia A or B in ICD-10, registered in MHR since 1977, had at least 1 registered prescription of Benefix or Refacto/Refacto AF in MHR since market authorization of respective product. Here, n= number of participants with available data for each category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Prescribed Dose Per Kilogram Bodyweight for Factor VIII and Factor IX Concentrates | Factor VIII | 27 IU per kilogram | Standard Deviation 10 |
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Prescribed Dose Per Kilogram Bodyweight for Factor VIII and Factor IX Concentrates | Factor IX | 37 IU per kilogram | Standard Deviation 11 |
Primary
Average Prescribed Frequency of Infusions Per Week Dispensed for Haemophilia A or B Participants With Prophylaxis
Time frame: For the duration of 11 years before the study start date (Day 1)
Population: MHR Benefix or Refacto/Refacto AF analysis set: all participants diagnosed with haemophilia A or B in ICD-10, registered in MHR since 1977, had at least 1 registered prescription of Benefix or Refacto/Refacto AF in MHR since market authorization of respective product. Here, N= number of participants with prophylaxis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Prescribed Frequency of Infusions Per Week Dispensed for Haemophilia A or B Participants With Prophylaxis | 3.9 infusions per week | Standard Deviation 1.6 |
| Benefix/Refacto/Refacto AF: Haemophilia B | Average Prescribed Frequency of Infusions Per Week Dispensed for Haemophilia A or B Participants With Prophylaxis | 3.1 infusions per week | Standard Deviation 2.4 |
Primary
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.
Time frame: For the duration of 11 years before the study start date (Day 1)
Population: MHR Benefix or Refacto/Refacto AF analysis set: all participants diagnosed with haemophilia A or B in ICD-10, registered in MHR since 1977, had at least 1 registered prescription of Benefix or Refacto/Refacto AF in MHR since market authorization of respective product. Here, n= number of participants with available data for each category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Relative Dose Intensity of Factor Concentrate Dispensed for Haemophilia A or B Participants on Prophylaxis Based on Dispensed Volume of Units | Adults | 88 percentage of factor concentrate | Standard Deviation 24 |
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Relative Dose Intensity of Factor Concentrate Dispensed for Haemophilia A or B Participants on Prophylaxis Based on Dispensed Volume of Units | Children/Adolescents | 103 percentage of factor concentrate | Standard Deviation 33 |
| Benefix/Refacto/Refacto AF: Haemophilia B | Average Relative Dose Intensity of Factor Concentrate Dispensed for Haemophilia A or B Participants on Prophylaxis Based on Dispensed Volume of Units | Children/Adolescents | 96 percentage of factor concentrate | Standard Deviation 22 |
| Benefix/Refacto/Refacto AF: Haemophilia B | Average Relative Dose Intensity of Factor Concentrate Dispensed for Haemophilia A or B Participants on Prophylaxis Based on Dispensed Volume of Units | Adults | 71 percentage of factor concentrate | Standard Deviation 33 |
Primary
Average Use of Factor Concentrate Per Surgery Event at Hospital for Invasive Procedures
Time frame: For the duration of 11 years before the study start date (Day 1)
Population: MHR Benefix or Refacto/Refacto AF analysis set: all participants diagnosed with haemophilia A or B in ICD-10, registered in MHR since 1977, had at least 1 registered prescription of Benefix or Refacto/Refacto AF in MHR since market authorization of respective product.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Use of Factor Concentrate Per Surgery Event at Hospital for Invasive Procedures | 13447 IU per surgery event | Standard Deviation 10695 |
| Benefix/Refacto/Refacto AF: Haemophilia B | Average Use of Factor Concentrate Per Surgery Event at Hospital for Invasive Procedures | 24171 IU per surgery event | Standard Deviation 20976 |
Primary
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.
Time frame: Data analyzed on study start Day 1 for the duration of 4 years (2005 to 2009)
Population: MHR Benefix or Refacto/Refacto AF analysis set: all participants diagnosed with haemophilia A or B in ICD-10, registered in MHR since 1977, had at least 1 registered prescription of Benefix or Refacto/Refacto AF in MHR since market authorization of respective product. Here, N= number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benefix/Refacto/Refacto AF: Haemophilia A | Gilbert Joint Score | 6 scores on a scale | Standard Deviation 8 |
Primary
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.
Time frame: Data analyzed on study start Day 1 for the duration of 6 years (2009 to 2015)
Population: MHR Benefix or Refacto/Refacto AF analysis set: all participants diagnosed with haemophilia A or B in ICD-10, registered in MHR since 1977, had at least 1 registered prescription of Benefix or Refacto/Refacto AF in MHR since market authorization of respective product. Here, N= number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benefix/Refacto/Refacto AF: Haemophilia A | Haemophilia Joint Health Score | 15 scores on a scale | Standard Deviation 17 |
Primary
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.
Time frame: For the duration of 11 years before the study start date (Day 1)
Population: MHR Benefix or Refacto/Refacto AF analysis set: all participants diagnosed with haemophilia A or B in ICD-10, registered in MHR since 1977, had at least 1 registered prescription of Benefix or Refacto/Refacto AF in MHR since market authorization of respective product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Benefix/Refacto/Refacto AF: Haemophilia A | Number of Joint Bleed, Muscle Bleeds and Other Bleed Events in Participants | Other bleed | 32 bleeds |
| Benefix/Refacto/Refacto AF: Haemophilia A | Number of Joint Bleed, Muscle Bleeds and Other Bleed Events in Participants | Joint bleed | 68 bleeds |
| Benefix/Refacto/Refacto AF: Haemophilia A | Number of Joint Bleed, Muscle Bleeds and Other Bleed Events in Participants | Muscle bleed | 179 bleeds |
Primary
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).
Time frame: For the duration of 11 years before the study start date (Day 1)
Population: MHR Benefix or Refacto/Refacto AF analysis set: all participants diagnosed with haemophilia A or B in ICD-10, registered in MHR since 1977, had at least 1 registered prescription of Benefix or Refacto/Refacto AF in MHR since market authorization of respective product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Benefix/Refacto/Refacto AF: Haemophilia A | Number of Participants With Consumption of Factor VIII, Factor IX, Factor rVIIa and/or aPCC Concentrate | Factor VIII | 33 Participants |
| Benefix/Refacto/Refacto AF: Haemophilia A | Number of Participants With Consumption of Factor VIII, Factor IX, Factor rVIIa and/or aPCC Concentrate | Factor IX | 53 Participants |
| Benefix/Refacto/Refacto AF: Haemophilia A | Number of Participants With Consumption of Factor VIII, Factor IX, Factor rVIIa and/or aPCC Concentrate | Factor rVIIa | 0 Participants |
| Benefix/Refacto/Refacto AF: Haemophilia A | Number of Participants With Consumption of Factor VIII, Factor IX, Factor rVIIa and/or aPCC Concentrate | Factor aPCC | 0 Participants |
Primary
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.
Time frame: For the duration of 11 years before the study start date (Day 1)
Population: MHR Benefix or Refacto/Refacto AF analysis set: all participants diagnosed with haemophilia A or B in ICD-10, registered in MHR since 1977, had at least 1 registered prescription of Benefix or Refacto/Refacto AF in MHR since market authorization of respective product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Benefix/Refacto/Refacto AF: Haemophilia A | Percentage of Participants on Prophylactic Treatment | 78 percentage of participants |
| Benefix/Refacto/Refacto AF: Haemophilia B | Percentage of Participants on Prophylactic Treatment | 56 percentage of participants |
Primary
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.
Time frame: For the duration of 11 years before the study start date (Day 1)
Population: MHR Benefix or Refacto/Refacto AF analysis set: all participants diagnosed with haemophilia A or B in ICD-10, registered in MHR since 1977, had at least 1 registered prescription of Benefix or Refacto/Refacto AF in MHR since market authorization of respective product.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Benefix/Refacto/Refacto AF: Haemophilia A | Percentage of Participants With Surgeries | Arthrodesis | 8 percentage of participants |
| Benefix/Refacto/Refacto AF: Haemophilia A | Percentage of Participants With Surgeries | Surgery on foot, nose, elbow, hand or shoulder | 8 percentage of participants |
| Benefix/Refacto/Refacto AF: Haemophilia A | Percentage of Participants With Surgeries | Surgery on hip | 7 percentage of participants |
| Benefix/Refacto/Refacto AF: Haemophilia A | Percentage of Participants With Surgeries | Surgery on knee | 11 percentage of participants |
| Benefix/Refacto/Refacto AF: Haemophilia A | Percentage of Participants With Surgeries | Tooth extraction | 17 percentage of participants |
| Benefix/Refacto/Refacto AF: Haemophilia A | Percentage of Participants With Surgeries | Venous port | 15 percentage of participants |
| Benefix/Refacto/Refacto AF: Haemophilia A | Percentage of Participants With Surgeries | Other surgeries | 34 percentage of participants |
Primary
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.
Time frame: For the duration of 11 years before the study start date (Day 1)
Population: MHR Benefix or Refacto/Refacto AF analysis set: all participants diagnosed with haemophilia A or B in ICD-10, registered in MHR since 1977, had at least 1 registered prescription of Benefix or Refacto/Refacto AF in MHR since market authorization of respective product. Here, N= number of participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Benefix/Refacto/Refacto AF: Haemophilia A | Percentage of Time on Refacto or Benefix | Percentage of time on Refacto | 0 days |
| Benefix/Refacto/Refacto AF: Haemophilia A | Percentage of Time on Refacto or Benefix | Percentage of time on Benefix | 19 days |
Primary
Total Number of Bleeds
Time frame: For the duration of 11 years before the study start date (Day 1)
Population: MHR Benefix or Refacto/Refacto AF analysis set: all participants diagnosed with haemophilia A or B in ICD-10, registered in MHR since 1977, had at least 1 registered prescription of Benefix or Refacto/Refacto AF in MHR since market authorization of respective product. Here, N= number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benefix/Refacto/Refacto AF: Haemophilia A | Total Number of Bleeds | 1.1 bleeds | Standard Deviation 1.4 |
Secondary
Average Annual Cost of Prescribed Factor Concentrate and Dispensed Replacement Treatment
Time frame: For the duration of 11 years before the study start date (Day 1)
Population: MHR Benefix or Refacto/Refacto AF analysis set: all participants diagnosed with haemophilia A or B in ICD-10, registered in MHR since 1977, had at least 1 registered prescription of Benefix or Refacto/Refacto AF in MHR since market authorization of respective product. Here, n= number of participants with available data for each category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Annual Cost of Prescribed Factor Concentrate and Dispensed Replacement Treatment | Prescribed Factor Concentrate | 2085000 SEK | Standard Deviation 875000 |
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Annual Cost of Prescribed Factor Concentrate and Dispensed Replacement Treatment | Dispensed Replacement Treatment | 1351000 SEK | Standard Deviation 944000 |
Secondary
Average Cost of Replacement Treatment Related to Invasive Procedures
Time frame: For the duration of 11 years before the study start date (Day 1)
Population: MHR Benefix or Refacto/Refacto AF analysis set: all participants diagnosed with haemophilia A or B in ICD-10, registered in MHR since 1977, had at least 1 registered prescription of Benefix or Refacto/Refacto AF in MHR since market authorization of respective product. Here, N= number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Cost of Replacement Treatment Related to Invasive Procedures | 71000 SEK | Standard Deviation 72000 |
Other Pre-specified
Average Annual Cost of Replacement Treatment Related to Invasive Procedures
Time frame: Data analyzed on study start Day 1 for Year 1 (2005) and Year 7 (2011)
Population: MHR Benefix or Refacto/Refacto AF analysis set: all participants diagnosed with haemophilia A or B in ICD-10, registered in MHR since 1977, had at least 1 registered prescription of Benefix or Refacto/Refacto AF in MHR since market authorization of respective product. Here, n= number of participants with available data for each category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Annual Cost of Replacement Treatment Related to Invasive Procedures | 2005 | 165000 SEK | Standard Deviation 143000 |
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Annual Cost of Replacement Treatment Related to Invasive Procedures | 2011 | 63000 SEK | Standard Deviation 51000 |
Other Pre-specified
Average Cost for Replacement Treatment Related to Invasive Procedures
The average cost for replacement treatment related to invasive procedures was derived from the percentage of total costs for dispensed replacement therapy and calculated as: cost of factor concentrate used for invasive procedures/ total cost of factor concentrate.
Time frame: Data analyzed on study start Day 1 for Year 1 (2005) and Year 7 (2011)
Population: MHR Benefix or Refacto/Refacto AF analysis set: all participants diagnosed with haemophilia A or B in ICD-10, registered in MHR since 1977, had at least 1 registered prescription of Benefix or Refacto/Refacto AF in MHR since market authorization of respective product. Here, n= number of participants with available data for each category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Cost for Replacement Treatment Related to Invasive Procedures | 2005 | 124 percentage of cost | Standard Deviation 245 |
| Benefix/Refacto/Refacto AF: Haemophilia A | Average Cost for Replacement Treatment Related to Invasive Procedures | 2011 | 14 percentage of cost | Standard Deviation 21 |