Disease-modifying treatment for polyneuropathy due to variant (hereditary) transthyretin amyloidosis in adults

Medication	Dosing	Administration	Common adverse effects
Patisiran	<100 kg ABW: 0.3 mg/kg IV once every 3 weeks ≥100 kg ABW: 30 mg once every 3 weeks	Pretreat (≥60 minutes prior to each dose) with: Glucocorticoid (eg, dexamethasone 10 mg IV) Acetaminophen (500 mg orally) H1 blocker (eg, diphenhydramine 50 mg IV or orally) H2 blocker (eg, famotidine 20 mg IV or orally) Vitamin A supplementation at RDA dosing during treatment^*	Infusion reactions Upper respiratory infections Rash Dyspepsia
Vutrisiran	25 mg SubQ once every 3 months	Vitamin A supplementation at RDA dosing during treatment^* Therapy administered by a healthcare professional	Injection site reaction Limb pain Arthralgias
Inotersen (limited availability^¶)	284 mg SubQ once weekly	Vitamin A supplementation at RDA dosing during treatment^* Monitor platelet count, creatinine, liver function tests at baseline, periodically during treatment, and for 8 weeks following treatment discontinuation May be self-administered following training by a healthcare professional	Thrombocytopenia Glomerulonephritis Transaminitis Injection site reaction Headache Fatigue Peripheral edema Nausea/vomiting Fever/myalgias
Eplontersen	45 mg SubQ once monthly	Vitamin A supplementation at RDA dosing during treatment^* May be self-administered following training by a healthcare professional	Thrombocytopenia Nausea/vomiting

Disease-modifying treatments for ATTRv may reduce levels of pathologic protein in affected tissue and may be used to slow the progression of ATTRv polyneuropathy or stabilize the disease. The selection of therapy is individualized, based on ease of use, availability, and risk of adverse symptoms. Refer to UpToDate content on management of neurologic manifestations of systemic amyloidosis for details on clinical use of disease-modifying therapies.

ABW: actual body weight; ATTRv: variant (hereditary) transthyretin amyloidosis; IV: intravenous; RDA: recommended daily allowance; SubQ: subcutaneous.

* If a patient develops ocular symptoms consistent with vitamin A deficiency (eg, night blindness), refer to an ophthalmologist.

¶ Inotersen was withdrawn from the market in the United States and Canada for commercial reasons; it remains available in some areas (eg, United Kingdom and European Union).

References:

Adams D, Gonzalez-Duarte A, O'Riordan WD, et al. Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. N Engl J Med 2018; 379:11.
Adams D, Tournev IL, Taylor MS, et al. Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial. Amyloid 2023; 30:1.
Benson MD, Waddington-Cruz M, Berk JL, et al. Inotersen treatment for patients with hereditary transthyretin amyloidosis. N Engl J Med 2018; 379:22.
Coelho T, Marques W Jr, Dasgupta NR, et al. Eplontersen for hereditary transthyretin amyloidosis with polyneuropathy. JAMA 2023; 330:1448.
Fontana M, Berk JL, Gillmore JD, et al. Vutrisiran in patients with transthyretin amyloidosis with cardiomyopathy. N Engl J Med 2025; 392:33.

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Disease-modifying treatment for polyneuropathy due to variant (hereditary) transthyretin amyloidosis in adults