Hereditary Transthyretin Amyloidosis (ATTRv) Cardiomyopathy (CM), Mixed Phenotype
Conditions
Keywords
transthyretin, amyloidosis, cardiomyopathy, tafamidis, polyneuropathy, progression
Brief summary
This study will examine the clinical effectiveness of Tafamidis in patients with Mixed Phenotype Hereditary Transthyretin Amyloidosis using data that already exist in patients' medical records.
Interventions
DRUGtafamidis
80 or 61 milligrams (mg)
Sponsors
Pfizer
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years at diagnosis * Diagnosed with ATTRv-CM, mixed phenotype * Treated with tafamidis (VYNDAQEL 80 mg \[four 20-mg tafamidis meglumine capsules\] orally once daily or VYNDAMAX 61 mg \[one 61-mg tafamidis capsule\] orally once daily) for ≥6 months * Have had ≥1 pre- and ≥2 post-treatment neurologic assessments
Exclusion criteria
* History of organ transplant * Wild-type TTR genotype * Individuals who are non-ambulatory * Prior treatment with any disease-modifying therapy (investigational or approved) alone or in combination, except tafamidis, as either VYNDAQEL 80 mg (four 20-mg tafamidis meglumine capsules) orally once daily or VYNDAMAX 61 mg (one 61-mg tafamidis capsule) orally once daily * Peripheral neuropathy attributed to causes other than ATTR amyloidosis (e.g., diabetes mellitus, B12 deficiency, HIV infection)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Neurologic Disease Progression: Number of Participants According to Muscle Weakness Assessment by Neuropathy Impairment Score (NIS) Subscale Score | Pre-treatment baseline period to post-treatment period (data for specified duration was extracted from medical records and observed retrospectively in this study from 08-Mar-2023 to 19-May-2023) | Neurologic disease progression meant worsening of neurologic function over the time, is assessed by NIS subscale score in this outcome measure. NIS is a composite neurologic impairment score that assesses muscle weakness, sensation, and reflexes by physical exam. NIS subscale for muscle weakness assessment has a score range from 0 (minimum value) to 192 (maximum value). Lower scores indicates normal to mild impairment. Participants were classified as: no change, increase or decrease in NIS subscale scores from pre-treatment baseline period to post-treatment period. Pre-treatment baseline period: at least 6 months and up to 12 months before treatment initiation. Post-treatment period: at least 6 months after treatment initiation with a +/- 3 months window. |
| Neurologic Disease Progression: Number of Participants According to Walking Capacity Assessment by Polyneuropathy Disability (PND) Score | Pre-treatment baseline period to post-treatment period (data for specified duration was extracted from medical records and observed retrospectively in this study from 08-Mar-2023 to 19-May-2023) | Neurologic disease progression meant worsening of neurologic function over the time, is assessed by PND score in this outcome measure. PND is a scoring system to assess participants' walking capacity. It consists of four stages from stage 0 (no impairment) to stage IV (confined to a wheelchair or bedridden). Lower scores indicates normal to mild impairment. Participants were classified as: no change, increase or decrease in PND scores from pre-treatment to post -treatment period. Pre-treatment baseline period: at least 6 months and up to 12 months before treatment initiation. Post-treatment period: at least 6 months after treatment initiation with a +/- 3 months window. |
| Neurologic Disease Progression: Number of Participants According to Muscle Strength Assessment by Medical Research Council (MRC) Scale | Pre-treatment baseline period to post-treatment period (data for specified duration was extracted from medical records and observed retrospectively in this study from 08-Mar-2023 to 19-May-2023) | Neurologic disease progression meant worsening of neurologic function over the time, is assessed by MRC scale in this outcome measure. MRC assessed muscle strength using a score of 0 (no contraction) to 5 (normal power), to grade the power of a particular muscle group in relation to the movement of a single joint. The higher scores mean a better outcome. Participants were classified as: no change, increase or decrease in MRC scale score from pre-treatment to post-treatment period. Pre-treatment baseline period: at least 6 months and up to 12 months before treatment initiation. Post-treatment period: at least 6 months after treatment initiation with a +/- 3 months window. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Modified Body Mass Index (mBMI) | Pre-treatment baseline period, post-treatment period (data for specified duration was extracted from medical records and observed retrospectively in this study from 08-Mar-2023 to 19-May-2023) | mBMI was calculated as the product of BMI in kilogram per meter square (kg/m\^2) and serum albumin in gram per litre (g/L) to compensate for peripheral edema. Pre-treatment baseline period: at least 6 months and up to 12 months before treatment initiation. Post-treatment period: at least 6 months after treatment initiation with a +/- 3 months window. |
Countries
United States
Participant flow
Recruitment details
Data of participants with mixed-phenotype variant transthyretin amyloid cardiomyopathy (ATTRv-CM) who initiated Tafamidis as either VYNDAQEL 80 milligram (mg) or VYNDAMAX 61 mg in a real world setting, were observed retrospectively in this study. Anonymized data was extracted from participant electronic medical records (EMR): MedStar health system in Washington D.C.(08-March-2023 to 19-May-2023).
Participants by arm
| Arm | Count |
|---|---|
| Tafamidis Eligible participants with ATTRv-CM who initiated Tafamidis as either VYNDAQEL 80 mg (four 20-mg tafamidis meglumine capsules) orally QD or VYNDAMAX 61 mg (one 61-mg tafamidis capsule) orally QD in a real world setting were included in this observational study. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Tafamidis |
|---|---|
| Age, Continuous | 72.20 Years STANDARD_DEVIATION 10.26 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 0 |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
Neurologic Disease Progression: Number of Participants According to Muscle Strength Assessment by Medical Research Council (MRC) Scale
Neurologic disease progression meant worsening of neurologic function over the time, is assessed by MRC scale in this outcome measure. MRC assessed muscle strength using a score of 0 (no contraction) to 5 (normal power), to grade the power of a particular muscle group in relation to the movement of a single joint. The higher scores mean a better outcome. Participants were classified as: no change, increase or decrease in MRC scale score from pre-treatment to post-treatment period. Pre-treatment baseline period: at least 6 months and up to 12 months before treatment initiation. Post-treatment period: at least 6 months after treatment initiation with a +/- 3 months window.
Time frame: Pre-treatment baseline period to post-treatment period (data for specified duration was extracted from medical records and observed retrospectively in this study from 08-Mar-2023 to 19-May-2023)
Population: All eligible participants whose data were included and observed in the study.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tafamidis | Neurologic Disease Progression: Number of Participants According to Muscle Strength Assessment by Medical Research Council (MRC) Scale | No change in scores | 8 Participants |
| Tafamidis | Neurologic Disease Progression: Number of Participants According to Muscle Strength Assessment by Medical Research Council (MRC) Scale | Increase in scores | 1 Participants |
| Tafamidis | Neurologic Disease Progression: Number of Participants According to Muscle Strength Assessment by Medical Research Council (MRC) Scale | Decrease in scores | 1 Participants |
Primary
Neurologic Disease Progression: Number of Participants According to Muscle Weakness Assessment by Neuropathy Impairment Score (NIS) Subscale Score
Neurologic disease progression meant worsening of neurologic function over the time, is assessed by NIS subscale score in this outcome measure. NIS is a composite neurologic impairment score that assesses muscle weakness, sensation, and reflexes by physical exam. NIS subscale for muscle weakness assessment has a score range from 0 (minimum value) to 192 (maximum value). Lower scores indicates normal to mild impairment. Participants were classified as: no change, increase or decrease in NIS subscale scores from pre-treatment baseline period to post-treatment period. Pre-treatment baseline period: at least 6 months and up to 12 months before treatment initiation. Post-treatment period: at least 6 months after treatment initiation with a +/- 3 months window.
Time frame: Pre-treatment baseline period to post-treatment period (data for specified duration was extracted from medical records and observed retrospectively in this study from 08-Mar-2023 to 19-May-2023)
Population: All eligible participants whose data were included and observed in the study. Here Number of Participants Analyzed signifies the number of participants who were evaluable for this outcome measure and had non-missing data.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tafamidis | Neurologic Disease Progression: Number of Participants According to Muscle Weakness Assessment by Neuropathy Impairment Score (NIS) Subscale Score | No change in scores | 2 Participants |
| Tafamidis | Neurologic Disease Progression: Number of Participants According to Muscle Weakness Assessment by Neuropathy Impairment Score (NIS) Subscale Score | Increase in scores | 2 Participants |
| Tafamidis | Neurologic Disease Progression: Number of Participants According to Muscle Weakness Assessment by Neuropathy Impairment Score (NIS) Subscale Score | Decrease in scores | 3 Participants |
Primary
Neurologic Disease Progression: Number of Participants According to Walking Capacity Assessment by Polyneuropathy Disability (PND) Score
Neurologic disease progression meant worsening of neurologic function over the time, is assessed by PND score in this outcome measure. PND is a scoring system to assess participants' walking capacity. It consists of four stages from stage 0 (no impairment) to stage IV (confined to a wheelchair or bedridden). Lower scores indicates normal to mild impairment. Participants were classified as: no change, increase or decrease in PND scores from pre-treatment to post -treatment period. Pre-treatment baseline period: at least 6 months and up to 12 months before treatment initiation. Post-treatment period: at least 6 months after treatment initiation with a +/- 3 months window.
Time frame: Pre-treatment baseline period to post-treatment period (data for specified duration was extracted from medical records and observed retrospectively in this study from 08-Mar-2023 to 19-May-2023)
Population: All eligible participants whose data were included and observed in the study.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tafamidis | Neurologic Disease Progression: Number of Participants According to Walking Capacity Assessment by Polyneuropathy Disability (PND) Score | No change in scores | 6 Participants |
| Tafamidis | Neurologic Disease Progression: Number of Participants According to Walking Capacity Assessment by Polyneuropathy Disability (PND) Score | Decrease in scores | 3 Participants |
| Tafamidis | Neurologic Disease Progression: Number of Participants According to Walking Capacity Assessment by Polyneuropathy Disability (PND) Score | Increase in scores | 1 Participants |
Secondary
Modified Body Mass Index (mBMI)
mBMI was calculated as the product of BMI in kilogram per meter square (kg/m\^2) and serum albumin in gram per litre (g/L) to compensate for peripheral edema. Pre-treatment baseline period: at least 6 months and up to 12 months before treatment initiation. Post-treatment period: at least 6 months after treatment initiation with a +/- 3 months window.
Time frame: Pre-treatment baseline period, post-treatment period (data for specified duration was extracted from medical records and observed retrospectively in this study from 08-Mar-2023 to 19-May-2023)
Population: All eligible participants whose data were included and observed in the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Tafamidis | Modified Body Mass Index (mBMI) | Pre-Treatment | 1001.06 (kg/m^2)*(g/L) | Standard Deviation 269.52 |
| Tafamidis | Modified Body Mass Index (mBMI) | Post-Treatment | 1070.92 (kg/m^2)*(g/L) | Standard Deviation 232.58 |