Is medication or surgery indicated for a patient who received Vutrisiran injection?

Vutrisiran Injection: Medical Indication and Clinical Context

Vutrisiran injection is medically indicated for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy (hATTR-PN) or transthyretin amyloidosis with cardiomyopathy (ATTR-CM), administered as 25 mg subcutaneously once every 3 months. 1

FDA-Approved Indications

Vutrisiran (AMVUTTRA) is specifically approved for:

• Treatment of polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults 1
• Treatment of cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis in adults 1

The medication works through RNA interference to degrade both mutant and wild-type TTR mRNA, resulting in reduction of serum TTR protein and TTR protein deposits in tissues 1

Clinical Evidence Supporting Use

For Polyneuropathy (hATTR-PN)

• In the HELIOS-A trial, vutrisiran significantly reduced neuropathy impairment versus placebo, with improvements in neuropathy-specific quality of life, gait speed, nutritional status, and disability scores 2
• Vutrisiran reduced mean serum TTR at steady state by 83%, with similar reductions regardless of Val30Met genotype status, weight, sex, age, or race 1

For Cardiomyopathy (ATTR-CM)

• In the HELIOS-B trial involving 655 patients, vutrisiran led to a 28% lower risk of death from any cause and recurrent cardiovascular events compared to placebo (HR 0.72; 95% CI 0.56-0.93; P=0.01) 3
• Treatment resulted in a 35% lower risk of death from any cause through 42 months (HR 0.65; 95% CI 0.46-0.90; P=0.01) 3
• Vutrisiran preserved functional capacity with less decline in 6-minute walk test distance (26.5 m difference; P<0.001) and quality of life scores (5.8 point difference in KCCQ-OS; P<0.001) 3
• Vutrisiran reduced outpatient worsening heart failure events by 34% (relative rate ratio 0.66; 95% CI 0.56-0.78) 4

Dosing and Administration

Standard dosing is 25 mg subcutaneously once every 3 months 1

• No dose adjustment required for patients ≥65 years of age 1
• No dose adjustment needed for mild or moderate renal impairment (eGFR ≥30 mL/min/1.73 m²) 1
• No dose adjustment needed for mild or moderate hepatic impairment 1
• Vutrisiran has not been studied in severe renal impairment, end-stage renal disease, or severe hepatic impairment 1

Critical Safety Considerations

Vitamin A supplementation (3,000 IU daily) is required during vutrisiran treatment because the medication reduces mean steady-state serum vitamin A by 62-65% 1, 5

Pharmacokinetic Profile

• Rapid absorption with peak plasma concentration at 4 hours post-dose 1
• Short plasma half-life of 5.2 hours (range 2.2-6.4 hours) 1
• Primarily distributes to the liver after subcutaneous dosing 1
• No drug accumulation occurs with repeated every-3-month dosing 1

Safety Profile

• Generally well tolerated with acceptable safety profile 2, 3
• Most common treatment-related adverse events were mild, transient injection site reactions (6.7% of patients) 6
• Pain in extremity and arthralgia occurred at greater incidence than placebo 2
• In HELIOS-B, adverse events occurred in 99% of vutrisiran patients vs 98% of placebo patients, with serious adverse events in 62% vs 67% respectively 3

Common Pitfalls and Caveats

Failure to provide vitamin A supplementation can lead to vitamin A deficiency-related complications including night blindness and other ocular manifestations 5, 1

The medication is NOT indicated for:

• Patients without confirmed transthyretin-mediated amyloidosis
• Pediatric patients (safety and effectiveness not established) 1
• Patients with severe renal or hepatic impairment (not studied) 1

Important monitoring considerations:

• Baseline and periodic assessment of vitamin A levels
• Ophthalmologic examination if visual symptoms develop 5
• Regular assessment of disease progression markers including neuropathy scores, functional capacity, and cardiac biomarkers 3, 4