Last reviewed: October 2018
Last updated: October  2018

Patisiran approved in Europe and the US for the treatment of polyneuropathy in adults with hereditary TTR amyloidosis

Patisiran is a novel agent that has been approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for treating polyneuropathy in adults caused by hereditary transthyretin (TTR) amyloidosis. [65] It is one of a new class of drugs called small interfering ribonucleic acid (siRNA) treatments, which work by silencing specific genes. Patisiran inhibits the production of TTR in the liver. It is the second of its class to be approved in Europe for this indication (inotersen was approved by the EMA in July 2018). It is the first therapeutic of its class to be approved in the US.

Approval was based on the results of an 18-month randomised placebo-controlled phase III trial (APOLLO). In the trial, patisiran reduced neurological impairment and improved quality of life compared with placebo in patients with TTR amyloidosis with polyneuropathy. The incidence and severity of adverse events were similar in patients receiving patisiran and placebo.

TTR amyloidosis is the most common form of inherited amyloidosis. It is a progressively debilitating disease that can lead to death. Liver transplantation is considered standard of care for these patients; however, this is limited to those who are fit enough for transplantation and who have a suitable donor. Patisiran provides clinicians with an alternative treatment option to liver transplantation in patients with TTR amyloidosis.

See Management: approach See Management: treatment algorithm

Original source of update

Summary

Definition

History and exam

Key diagnostic factors

  • presence of risk factors
  • jugular venous distention
  • lower extremity oedema
  • periorbital purpura
  • macroglossia

Other diagnostic factors

  • fatigue
  • weight loss
  • dyspnoea on exertion
  • paraesthesia
  • claudication
  • nausea
  • abdominal cramps
  • alternating bowel habit
  • light-headed/orthostatic hypotension
  • submandibular salivary gland enlargement
  • hepatomegaly
  • shoulder pad sign
  • diffuse muscular weakness
  • sensory neuropathy
  • Tinel's sign
  • Phalen's manoeuvre

Risk factors

  • monoclonal gammopathy of undetermined significance (MGUS)
  • inflammatory polyarthropathy
  • chronic infections
  • inflammatory bowel disease
  • Castleman's disease
  • familial periodic fever syndromes

Diagnostic investigations

1st investigations to order

  • serum immunofixation
  • urine immunofixation
  • immunoglobulin free light chain assay
  • bone marrow biopsy
Full details

Investigations to consider

  • tissue biopsy
  • immunohistological studies of amyloid deposits
  • mass spectrometry
  • immuno-electron microscopy
  • genetic testing
  • serum amyloid P (SAP) scintigraphy scan
  • FBC
  • comprehensive metabolic profile
  • 24-hour urine collection
  • serum troponin level
  • B-type natriuretic peptide
  • beta-2-microglobulin
  • ECG
  • echocardiogram
  • Doppler echo with strain
  • cardiac MRI
Full details

Treatment algorithm

Contributors

Authors VIEW ALL

Morie A. Gertz

Seidler Jr. Professor of Medicine

Consultant in Hematology

Chair Emeritus of the Department of Medicine

Mayo Distinguished Clinician

Mayo Clinic College of Medicine

Rochester

MN

Disclosures

MAG declares that he has received honoraria from Celgene Corporation, Prothena Corporation Plc, Onyx Pharmaceuticals, Alnylam, and Ionis Pharmaceuticals. MAG is also an author of several references cited in this monograph.

Peer reviewers VIEW ALL

Associate Professor of Medicine

Director

Program for Multiple Myeloma and Related Diseases

Princess Margaret Hospital

Toronto

Ontario

Canada

Disclosures

DR has been reimbursed by Millennium Pharmaceuticals, Inc and Johnson and Johnson, the manufacturers of bortezomib, for attending several conferences, for speaking at educational meetings, and for consulting work. She has also been reimbursed by Celgene, the manufacturer of lenalidomide and thalidomide, for attending several symposia and serving as a speaker.

Assistant Professor of Medicine and Oncology

Division of Hematology/Oncology

Wayne State University School of Medicine

Barbara Ann Karmanos Cancer Institute

Detroit

MI

Disclosures

JZ declares that he has no competing interests.

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