The Effect Of Tafamidis For The Transthyretin Amyloid Polyneuropathy Patients With V30M Or Non-V30M Transthyretin

TTR tetramer level for each plasma sample was assessed using a validated immunoturbidimetric assay before and after urea denaturation. The Fraction of Initial (FOI) tetramer concentration is the ratio of the measured TTR tetramer concentration after denaturation to the measured TTR tetramer average concentration before denaturation. TTR tetramer stabilization is based on the difference between the on-treatment FOI and the baseline FOI expressed as a percentage of the baseline FOI. A patient who has the "TTR stabilization" is defined as the patient whose percent stabilization is equal to or more than 32%.

The NIS provides a total body single score of neuropathic deficits (score range: 0-122, higher score = more deficit), comprising subset scores for cranial nerves, muscle weakness, reflexes, and sensation (based on mean of 2 scores in 1 week period; each item scored separately for left and right). The NIS-LL is a subscale that provides a score for the lower limbs functions (muscle weakness, reflexes and sensation in great toe) and has a score range of 0-44 (higher score = more deficit). The NIS-UL is a subscale that provides a score for the upper body functions (muscle weakness [including cranial nerves], reflexes and sensation in finger) and has a score range of 0-78 (higher score = more deficit). The components for cranial nerves and muscle weakness are scored from 0 (Normal) to 4 (Paralysis), and those for reflexes and sensation from 0 (Normal) to 2 (Absent). For all items, higher scores indicate greater impairment.

Norfolk QOL-DN is a 35-item participant-rated questionnaire. It consists of 5 domains: Physical Functioning/Large Fiber [score range: -4 - 56] , Activities of Daily Living (ADL) [0 - 20], Symptoms [0 - 32], Small Fiber [0 - 16] and Autonomic [0 - 12]. Total of quality of life (TQOL) score is the sum of all five domains with a range of -4 to 136 (Pfizer Data Standards). Higher scores on each item of the Norfolk QOL-DN TQOL indicate worse quality of life.

The Σ7 NTs nds measures primarily large-fiber function. It is a composite score derived from five NCS attributes (peroneal nerve distal motor latency, peroneal nerve compound muscle action potential, peroneal nerve motor conduction velocity, tibial nerve distal motor latency, and sural nerve sensory nerve action potential amplitude) along with VDT obtained in great toes by Quantitative Sensory Testing (QST), and HRDB value. It is defined as 7 times the mean of non-missing values of, the five normal deviates of NCS, HRDB, and average normal deviate for VDT of toes. Score was determined through reference to normal values for age, sex, height and abnormalities scored. Total score range is approximately -26 to 26, where higher score=worse nerve function.

The Σ3 NTSF nds measures small-fiber function. It is a composite score defined as 3 times the mean of non-missing values of normal deviates of cooling threshold for lower limbs, heat pain intermediate response for lower limbs, and HRDB. The total score range is approximately -11.2 to 11.2, with a higher score demonstrating worse nerve function.

The mBMI was calculated by multiplying the BMI (the weight in kilograms divided by the square of the height in meters) by serum albumin level (gram/liter). Change in mBMI was calculated as the mBMI at the given week minus the Baseline mBMI.

Ambulatory status was evaluated using walking ability scale in polyneuropathy disability score. The ambulatory status was evaluated as: 0=Good, 1=Sensory disturbances in the feet but able to walk without difficulty, 2=Some difficulties with walking but can walk without aid, 3a=Able to walk with 1 stick or crutch, 3b=Able to walk with 2 sticks or crutches, 4=Not ambulatory, confined to a wheelchair or bedridden.

TTR tetramer was assessed using a validated immunoturbidimetric assay. The TTR tetramer level for each plasma sample was measured before and after urea denaturation. The Fraction of Initial (FOI) tetramer concentration is the ratio of the measured TTR tetramer concentration after denaturation to the measured TTR tetramer concentration before denaturation. TTR tetramer stabilization is based on the difference between the on-treatment FOI and the baseline FOI expressed as a percentage of the baseline FOI. A patient who has the "TTR stabilization" is defined as the patient whose percent stabilization is equal to or more than 32%.