A study of patients with hereditary transthyretin amyloidosis (ATTRv) and wild-type transthyretin amyloidosis (ATTRwt) that have been enrolled in B3461028 and B3461045 studies in Spain - exposed to tafamidis 61mg for ≥12 months with polyneuropathy (PN) have kept going to their multisystemic follow-ups (neuro/ophthalmo/gastrointestinal) ≥12 months.
Study Type
OBSERVATIONAL
Enrollment
5
61 milligrams (mg) as received in studies B3461028 and B3461045
Hospital Universitari de Bellvitge
Barcelona, Spain
Hospital Clinico San Carlos
Madrid, Spain
Hospital Son Llatzer
Palma de Mallorca, Spain
Change in Neuropathy Impairment Score (NIS) at Month 12 for ATTRv
NIS (Neuropathy Impairment Score) is a clinically important, sensitive measure of individual neurological function, assessing sensory function, reflexes, and muscle weakness. NIS score ranged from 0 to 244, with higher score indicating greater disability or impairment. The rate of change was calculated from last follow-up.
Time frame: Baseline and Month 12 (data collected and analyzed over 22 days)
Change in NIS for ATTRv
NIS (Neuropathy Impairment Score) is a clinically important, sensitive measure of individual neurological function, assessing sensory function, reflexes, and muscle weakness. NIS score ranged from 0 to 244, with higher score indicating greater disability or impairment. The rate of change was calculated from last follow-up.
Time frame: Baseline, Month 6, 18, 24 and 36 after the start of treatment (data collected and analyzed over 22 days)
Change in Neuropathy Impairment Score - Lower Limbs (NIS-LL) for ATTRv
NIS-LL (Neuropathy Impairment Score Lower Limbs) is a clinically important, sensitive measure of neurological function in individuals, assessing sensory function, reflexes, and muscle weakness of the lower limbo. NÍS-LL assessed muscle weakness, reflexes, sensation. Each item is scored separately for left and right limbs. Components of muscle weakness:0(normal) to4(paralysis), higher score=more weakness; reflexes, sensation:0=normal, 1=decreased, or 2=absent. Total NIS-LL score range 0-88, higher score=more impairment. The rate of change was calculated from last follow-up.
Time frame: Baseline, Month 6, 12, 18, 24 and 36 after the start of treatment (data collected and analyzed over 22 days)
Change in Norfolk Quality of Life- Diabetic Neuropathy (Norfolk QOL-DN) for ATTRv
Norfolk Quality of Life Questionnaire for Diabetic Neuropathy is a standardized and validated instrument that assesses the effect of polyneuropathy on the functionality and quality of life of the individual. Norfolk QOL-DN: 35-item participant-rated questionnaire is used to assess impact of diabetic neuropathy on the quality of life of participants with diabetic neuropathy; Item 1 to 7: related to symptoms and presence of symptom was assessed as 1 and absence was assessed as 0. Item 8-35: related to activities of daily living and scored on a 5-point Likert scale, where 0= no problem and 4= severe problem (except item 32, where -2= much better, 0=about the same, 2=much worse). TQOL= sum of all the items, total possible score range= -4 to 138, where higher score=worse quality of life.
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Time frame: Baseline, Month 6, 12, 18, 24 and 36 after the start of treatment (data collected and analyzed over 22 days)
Change in COMPASS-31 for ATTRv
COMPASS-31 (Composite Autonomic Symptom Score 31) is a questionnaire designed to assess the severity and functional ability in participants with autonomic dysfunction. COMPASS-31 total score ranged from 0 to 100; where 0=Lesser severity of dysautonomia and 100=Greater severity of dysautonomia.
Time frame: Baseline, Month 6, 12, 18, 24 and 36 after the start of treatment (data collected and analyzed over 22 days)
Change in Familial Amyloid Polyneuropathy Specific Rasch-Built Overall Disability Scale (FAP-RODs) for ATTRv
FAP-RODS is a questionnaire that assessed the effect of neuropathy on daily activities. FAP-RODS total score ranged from 0 to 68; where, 0=Lower ability to perform daily activities and 68=Greater ability to perform daily activities.
Time frame: Baseline, Month 6, 12, 18, 24 and 36 after the start of treatment (data collected and analyzed over 22 days)
Number of Participants According to Familiar Amyloidotic Polyneuropathy Stage (FAP) for ATTRv
FAP is a stage system based on symptom severity and disease progression. FAP stages included: Asymptomatic; Free ambulation (walking without support): stage 1; Supportive ambulation (walking with support): stage 2; Wheelchair-bound or bedridden: stage 3.
Time frame: Month 18, 24 and 30 months after the start of treatment (data collected and analyzed over 22 days)
Percentage of Participants Who do Not Have Stage Progression in the PND Score for ATTRv
PND is a staging system that assess the degree of neuropathic dysfunction and its impact on ambulation. PND stages included: Asymptomatic; Stage I: Sensory disturbances, normal gait; Stage II: Sensory disturbances, altered gait not requiring support; IIIA: Gait requiring one support; IIIB: Gait requiring two supports; IV: Wheelchair or bedside. Participants who did not change to higher stages compared to the start of treatment was reported as Unchanged and those who progressed to higher stages were reported under Staging up.
Time frame: From Baseline to Month 30 (data collected and analyzed over 22 days)
Percentage of Responders to Treatment for ATTRv
Percentage of responders to treatment at Month 12 was defined as participants who achieved the change from baseline of less than 4 points in the NIS and participants who achieved the change from baseline of less than 2 points in the NIS-LL were reported in this outcome measure.
Time frame: Month 12 (data collected and analyzed over 22 days)
Number of Participants With R-R Interval Variability for ATTRv
Number of participants with R-R interval variability (altered/unaltered) was reported in this outcome measure.
Time frame: Month 18, 24 and 30 (data collected and analyzed over 22 days)
Modified Body Mass Index (mBMI) for ATTRv
BMI was calculated by weight divided by height squared and measured as kilogram per square meter (kg/m\^2). mBMI was calculated by multiplying BMI by serum albumin levels \[gram/liter (g/L)\].
Time frame: Month 18, 24 and 30 after start of treatment (data collected and analysed over 22 days)
Ulnar/Sural Sensory Nerve Action Potential Amplitude (SNAP) for ATTRv
Sural sensory nerve action potential amplitude (in microvolts) was measured using electromyography of the left lower limb.
Time frame: Month 24 and 30 after the start of treatment (data collected and analyzed over 22 days)
Ulnar/Peroneal Compound Muscle Action Potential Amplitude (CMAP) for ATTRv
Peroneal motor nerve compound muscle action potential amplitude was measured using electromyography of the left lower limb.
Time frame: Month 24 and 30 after the start of treatment (data collected and analyzed over 22 days)
Change in NIS for ATTRwt
NIS (Neuropathy Impairment Score) was a clinically important, sensitive measure of individual neurological function, assessing sensory function, reflexes, and muscle weakness. NIS score ranged from 0 to 244, with higher score indicating greater disability or impairment. The rate of change was calculated from last follow-up.
Time frame: Baseline, Month 6, 12, 18, 24 and 36 after the start of treatment (data collected and analyzed over 22 days)
Change in NIS-LL for ATTRwt
NIS-LL (Neuropathy Impairment Score Lower Limbs) was clinically important, sensitive measure of neurological function in individuals, assessing sensory function, reflexes, and muscle weakness of the lower limbo. NÍS-LL assessed muscle weakness, reflexes, sensation. Each item scored separately for left and right limbs. Components of muscle weakness:0(normal) to4(paralysis), higher score=more weakness; reflexes, sensation:0=normal, 1=decreased, or 2=absent. Total NIS-LL score range 0-88, higher score=more impairment. The rate of change was calculated from last follow-up.
Time frame: Baseline, Month 6, 12, 18, 24 and 36 after the start of treatment (data collected and analyzed over 22 days)
Change in Norfolk QOL-DN for ATTRwt
Norfolk Quality of Life Questionnaire for Diabetic Neuropathy was a standardized and validated instrument that assesses the effect of polyneuropathy on the functionality and quality of life of the individual. Norfolk QOL-DN: 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on the quality of life of participants with diabetic neuropathy; Item 1 to 7: related to symptoms and presence of symptom was assessed as 1 and absence was assessed as 0. Item 8-35: related to activities of daily living and scored on a 5-point Likert scale, where 0= no problem and 4= severe problem (except item 32, where -2= much better, 0=about the same, 2=much worse). TQOL= sum of all the items, total possible score range= -4 to 138, where higher score=worse quality of life.
Time frame: Baseline, Month 6, 12, 18, 24 and 36 after the start of treatment (data collected and analyzed over 22 days)
Change in COMPASS-31 for ATTRwt
COMPASS-31 (Composite Autonomic Symptom Score 31) was a questionnaire designed to assess the severity and functional ability in participants with autonomic dysfunction. COMPASS-31 total score ranged from 0 to 100; where 0=Lesser severity of dysautonomia and 100=Greater severity of dysautonomia.
Time frame: Baseline, Month 6, 12, 18, 24 and 36 after treatment initiation
Change in FAP-RODs for ATTRwt
FAP-RODS is a questionnaire that assessed the effect of neuropathy on daily activities. FAP-RODS total score ranged from 0 to 68; where, 0=Lower ability to perform daily activities and 68=Greater ability to perform daily activities.
Time frame: Baseline, Month 6, 12, 18, 24 and 36 after the start of treatment (data collected and analyzed over 22 days)
Number of Participants According to FAP Stage for ATTRwt
FAP stage is a staging system based on symptom severity and disease progression. FAP stages included: Asymptomatic; Free ambulation (Walking without support): stage 1; Supportive ambulation (Walking with support): stage 2; Wheelchair-bound or bedridden: stage 3.
Time frame: Month 18, 24 and 30 months after the start of treatment (data collected and analyzed over 22 days)
Percentage of Participants Who do Not Have Stage Progression in the PND Score for ATTRwt
PND was a simple staging system according to the degree of neuropathic dysfunction and its impact on ambulation. PND stages included: Asymptomatic: I Sensory disturbances, normal gait: II Sensory disturbances, altered gait not requiring support: IIIA Gait requiring one support: IIIB Gait requiring two supports: IV Wheelchair or bedside). Participants who did not change to higher stages compared to the start of treatment was reported as Unchanged and those who progressed to higher stages were reported under Staging up.
Time frame: From Baseline to Month 30 (data collected and analysed over 22 days)
Percentage of Responders to Treatment for ATTRwt
Percentage of responders to treatment was defined as participants who achieved the change from baseline of less than 4 points in the NIS and participants who achieved the change from baseline of less than 2 points in the NIS-LL were reported in this outcome measure.
Time frame: Month 12 (data collected and analyzed over 22 days)
Number of Participants With R-R Interval Variability for ATTRwt
Number of participants with R-R interval variability (altered/unaltered) was reported in this outcome measure.
Time frame: Month 18, 24 and 30 (data collected and analyzed over 22 days)
mBMI for ATTRwt
BMI was calculated by weight divided by height squared and measured as kilogram per square meter (kg/m\^2).
Time frame: Month 18, 24 and 30 after start of treatment (data collected and analysed over 22 days)
Ulnar/Sural SNAP Score for ATTRwt
Sural sensory nerve action potential amplitude (in microvolts) was measured using electromyography of the left lower limb.
Time frame: Month 24 and 30 after the start of treatment (data collected and analyzed over 22 days)
Ulnar/Peroneal CMAP Score for ATTRwt
Peroneal motor nerve compound muscle action potential amplitude (in millivolts) was measured using electromyography of the left lower limb.
Time frame: Month 24 and 30 after the start of treatment (data collected and analyzed over 22 days)
Number of Participants With Carpal Tunnel Syndrome
Number of participants with carpal tunnel syndrome were reported in this outcome measure.
Time frame: At baseline (data collected and analyzed over 22 days)
Number of Participants With Lumbar Stenosis
Number of participants with lumbar stenosis were reported in this outcome measure.
Time frame: At baseline (data collected and analyzed over 22 days)
Number of Participants With Gastrointestinal Disturbances
Number of participants with gastrointestinal disturbances were reported in this outcome measure.
Time frame: Month 18, 24 and 30 after the start of treatment (data collected and analyzed over 22 days)
Number of Participants With Unintentional Weight Loss
Number of participants with unintentional weight loss were reported in this outcome measure.
Time frame: Month 18, 24 and 30 after the start of treatment (data collected and analyzed over 22 days)
Number of Participants With Urological Disturbances
Number of participants with urological disturbances were reported in this outcome measure.
Time frame: Month 18, 24 and 30 after the start of treatment (data collected and analyzed over 22 days)
Number of Participants With Ophthalmological Disturbances
Number of participants with ophthalmological disturbances were reported in this outcome measure.
Time frame: Month 18, 24 and 30 after the start of treatment (data collected and analyzed over 22 days)
Number of Participants With Central Nervous System (CNS) Disturbances
Number of participants with CNS disturbances were reported in this outcome measure.
Time frame: Month 18, 24 and 30 after the start of treatment (data collected and analyzed over 22 days)
Number of Participants With Symptoms of Autonomic Neuropathy
Number of participants with symptoms of autonomic neuropathy including impaired sweating, sexual dysfunction, orthostatic hypotension were reported in this outcome measure.
Time frame: Month 18, 24 and 30 after the start of treatment (data collected and analyzed over 22 days)
Number of Participants With Symptoms of Peripheral Neuropathy
Number of participants with symptoms of peripheral neuropathy (allodynia and paresthesia) were reported in this outcome measure.
Time frame: At baseline (data collected and analyzed over 22 days)