Clinical Pearls for SPINRAZA (Nusinersen)

1. Spinal Muscular Atrophy (SMA): This is a genetic condition that affects the motor neurons in the spinal cord. People with SMA have a deficiency in the SMN protein, leading to muscle weakness and atrophy.

2. How Spinraza Works: Spinraza is an antisense oligonucleotide, which means it helps modify the genetic instructions for producing the SMN protein. By doing this, it increases the levels of SMN protein in the body, thereby helping improve muscle function and prevent further deterioration.

Mechanism of Action:

• Nusinersen acts as an antisense oligonucleotide targeting the SMN2 gene, leading to increased expression of functional SMN protein, crucial for motor neuron function.

Administration

• Intrathecal Injection: SPINRAZA is administered via intrathecal injection, which involves delivering the drug directly into the cerebrospinal fluid (CSF) surrounding the spinal cord. This procedure should be performed by healthcare professionals experienced in lumbar punctures.

• Dosing Schedule:
• Loading Doses: The treatment begins with four loading doses. The first three doses are given at 14-day intervals, and the fourth dose is administered 30 days after the third dose.
• Maintenance Doses: Following the loading doses, SPINRAZA is administered every four months as a maintenance dose.

• Preparation and Procedure:
• Allow SPINRAZA to warm to room temperature before administration and use within four hours of removal from the vial.
• Prior to injection, 5 mL of CSF should be removed to prevent increased intracranial pressure.
• The injection is administered over 1 to 3 minutes, and imaging techniques like ultrasound may be used to guide needle placement, especially in younger patients or those with spinal deformities.

Safety and Monitoring

• Common Side Effects: Patients may experience lower respiratory infections, fever, constipation, headache, vomiting, back pain, and post-lumbar puncture syndrome.

• Laboratory Monitoring:
• Blood Tests: Perform blood tests to monitor platelet counts and coagulation parameters before starting treatment and prior to each dose, due to the risk of thrombocytopenia and coagulation abnormalities.
• Urine Tests: Conduct urine tests to monitor kidney function, as there is a risk of renal toxicity, including glomerulonephritis.

Patient Education

• Treatment Expectations: Educate patients and caregivers about the treatment schedule and the importance of adhering to it for optimal outcomes. Explain that individual results may vary based on factors such as disease severity and treatment initiation timing.

• Side Effect Management: Inform patients about potential side effects and advise them to report any unusual symptoms, especially signs of bleeding or kidney issues, to their healthcare provider promptly.

• Emotional Support: Recognize the emotional impact of treatment on patients and their families. Providing support and resources can help manage expectations and improve the treatment experience.

Clinical Trial Outcomes

1. Interim Analysis:
• Responders:
• 40% of patients receiving SPINRAZA showed improvement in motor milestones compared to 0% in the control group.
• Final Analysis:
• 51% of SPINRAZA patients were responders.
• Statistically significant differences were observed in motor milestone responses and overall survival rates.

2. Mortality and Ventilation Events:
• Statistical analysis revealed a 47% reduction in death or permanent ventilation risk in the SPINRAZA group (p=0.005).
• Median time to death/ventilation was significantly longer for SPINRAZA patients compared to those receiving sham treatment.

3. Motor Skill Assessment:
• The Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) showed favorable results in muscle skill evaluations amongst SPINRAZA-treated individuals.