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Understand how to diagnose and treat the polyneuropathy of hATTR amyloidosis in adults

ASK now
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about family history and red-flag symptoms

Hereditary transthyretin-mediated (hATTR) amyloidosis is a debilitating disease with a median survival of 4.7 years after diagnosis. Obtaining a complete family history is an integral step toward recognizing and accelerating the diagnosis of this inherited disease.1-3

To enable a timely diagnosis of hATTR amyloidosis, it is critical to ask patients about their complete clinical history, including symptoms of the most common manifestations of the disease.2-4

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Sensory-motor neuropathy

Typically length-dependent, symmetric, small-fiber neuropathy symptoms that progress over time

  • Neuropathic pain
  • Paresthesia
  • Bilateral carpal tunnel syndrome
  • Weakness
  • Loss of fine motor control
  • Difficulty walking
autonomic neuropathy icon

Autonomic neuropathy

May affect a variety of organ systems including cardiovascular, gastrointestinal, and genitourinary systems

  • Orthostatic hypotension
  • Abnormal sweating
  • Nausea and vomiting
  • Constipation and/or diarrhea
  • Urinary and/or fecal incontinence
  • Early satiety and wasting
  • Sexual dysfunction
cardiac maifestation

Cardiac manifestations

May include conduction abnormalities, arrhythmias, heart failure

Rapid worsening of these signs and symptoms should also alert you to the possibility of hATTR amyloidosis.2

Read more about the variable clinical presentation of hATTR amyloidosis »
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the evidence of disease through diagnostic tools

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IDENTIFY

When you identify a patient who may have hATTR amyloidosis, you can choose from a number of different tests that can help assist in the assessment and diagnosis of hATTR amyloidosis2,4-6

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CONFIRM

Several tests are available to help confirm the presence of amyloid deposits and to help make a diagnosis of hATTR amyloidosis, including genetic testing, scintigraphy, and tissue biopsy3,4,6

ViewHide tests and example results  
IDENTIFY4-8
Electromyography (EMG)

Electromyography (EMG)

  • Fibrillation potentials and positive sharp waves signifying axonal injury and active denervation
  • Volitional motor unit recruitment consistent with chronic denervation and reinnervation
Nerve conduction study (NCS)

Nerve conduction study (NCS)

  • Axonal large-fiber polyneuropathy with greater sensory involvement than motor
  • Absent or reduced sensory nerve conduction amplitudes
  • Reduced or absent motor nerve conduction amplitudes with normal to mildly slowed conduction velocities
Quantitative sudomotor axon reflex test (QSART)

Quantitative sudomotor axon reflex test (QSART)

  • Diminished sweat volume
Sympathetic skin response (SSR)

Sympathetic skin response (SSR)

  • Reduced amplitude in response to electrical stimuli
Heart rate deep breathing

Heart rate deep breathing

  • Limited heart rate variability in response to deep breathing
Tilt table

Tilt table

  • Orthostatic hypotension in response to upright tilt
Valsalva maneuver

Valsalva maneuver

  • Rapid blood pressure decline in response to exhalation against a closed airway
Echocardiography

Echocardiography

  • Left ventricular wall thickening
  • Refractile myocardium (granular sparkling)
  • Low tissue Doppler velocities, reduced longitudinal strain that may be more pronounced at the base than the apex
Electrocardiography (ECG)

Electrocardiography (ECG)

  • Low voltage
  • Pseudo-infarction pattern
  • Progressive reduction in QRS voltage over time
  • AV block
Cardiac magnetic resonance imaging (CMRI)

Cardiac magnetic resonance imaging (CMRI)

  • Left ventricular wall thickening
  • Subendocardial late gadolinium enhancement
CONFIRM3,4,6
Genetic testing

Genetic testing

  • Detection of a mutation in the TTR gene
Scintigraphy

Scintigraphy

  • Cardiac uptake of 99mTc-PYP or 99mTc-DPD
Tissue biopsy

Tissue biopsy

  • Green birefringence under polarized light when stained with Congo red
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that ONPATTRO® (patisiran) can reverse the polyneuropathy manifestations of the disease9,10

Noval RNAi icon

Novel RNAi-based approach that targets the pathogenic protein at its source9

reversal in neuropathy

Reversal in neuropathy impairment from baseline9

  • Mean change from baseline at 18 months in mNIS+7 of -6.0 points vs 28.0 with placebo, a treatment difference of -34 points (95% CI: -39.9, -28.1; p<0.001)
  • 56% of patients treated with ONPATTRO experienced reversal in neuropathy impairment from baseline at 18 months vs 4% of patients treated with placebo
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Improvement in quality of life9,10

  • Mean change from baseline at 18 months in Norfolk QoL-DN of -6.7 points vs 14.4 with placebo, a treatment difference of -21.1 points (95% CI: -27.2, -15.0; p<0.001)

ONPATTRO demonstrated a benefit versus placebo in the treatment of the polyneuropathy of hATTR amyloidosis at 18 months.9,10

Read more about the efficacy of ONPATTRO »

Study design9

The efficacy of ONPATTRO was demonstrated in a randomized, double-blind, placebo-controlled, multicenter clinical trial in adults with hATTR amyloidosis with polyneuropathy. Patients were randomized to receive ONPATTRO 0.3 mg/kg (N=148) or placebo (N=77) via intravenous infusion once every 3 weeks for 18 months.

Primary endpoint

The modified Neuropathy Impairment Score + 7 (mNIS+7) is an objective 304-point assessment of neuropathy that measures cranial nerve function, muscle strength, reflexes, postural blood pressure, quantitative sensory testing, and peripheral nerve electrophysiology, with higher scores representing worsening neuropathy.

Key secondary endpoint

Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) scale is a patient-reported assessment that evaluates neuropathy in the following domains: physical functioning/large fiber neuropathy, activities of daily living, symptoms, small fiber neuropathy, and autonomic neuropathy (score range -4 to 136), with higher scores representing worsening quality of life.

ASK now

Now is the time to act.

hATTR amyloidosis is a rapidly progressive disease that can lead to significant disability and reduced quality of life for patients.6,11,12

Use the ASKnow guide to learn about how you can diagnose and treat the polyneuropathy of hATTR amyloidosis in adults

ASK now Download the ASKnow guide »
10MWT=10-meter walk test; 99mTc-DPD=technetium-99m-3,3-diphosphono-1,2-propanodicarboxylic acid; 99mTc-PYP=technetium-99m-pyrophosphate; CI=confidence interval; COMPASS 31=Composite Autonomic Symptom Score 31; mNIS+7=modified Neuropathy Impairment Score + 7; NIS-W=Neuropathy Impairment Score-Weakness; Norfolk QoL-DN=Norfolk Quality of Life-Diabetic Neuropathy; RNAi=ribonucleic acid interference.

References:

  1. Swiecicki PL, Zhen DB, Mauermann ML, et al. Amyloid. 2015;22(2):123-131.
  2. Conceição I, González-Duarte A, Obici L, et al. J Peripher Nerv Syst. 2016;21(1):5-9.
  3. Adams D, Suhr OB, Hund E, et al. Curr Opin Neurol. 2016;29(suppl 1):S14-S26.
  4. Dharmarajan K, Maurer MS. J Am Geriatr Soc. 2012;60(4):765-774.
  5. Shin SC, Robinson-Papp J. Mt Sinai J Med. 2012;79(6):733-748.
  6. Ando Y, Coelho T, Berk JL, et al. Orphanet J Rare Dis. 2013;8:31.
  7. Castro J, Miranda B, Castro I, et al. Clin Neurophysiol. 2016;127(5):2222-2227.
  8. Falk RH, Quarta CC. Heart Fail Rev. 2015;20(2):125-131.
  9. ONPATTRO [package insert]. Cambridge, MA: Alnylam Pharmaceuticals, Inc; 2018.
  10. Adams D, Gonzalez-Duarte A, O’Riordan WD, et al. N Engl J Med. 2018;379(1):11-21.
  11. Coutinho P, Martins da Silva A, Lopes Lima JL, et al. Excerpta Medica;1980:88-98.
  12. Vinik EJ, Vinik AI, Paulson JF, et al. J Peripher Nerv Syst. 2014;19:104-119.