What are the recommended treatment approaches for adults with Spinal Muscular Atrophy (SMA) type 3?

Treatment of Adult SMA Type 3

Risdiplam (EVRYSDI) is the recommended first-line treatment for adults with SMA type 3, administered orally at 5 mg once daily, offering a well-tolerated systemic therapy that improves or stabilizes motor function. 1

Primary Treatment: Risdiplam

Dosing and Administration

• Adults with SMA type 3 weighing ≥20 kg should receive 5 mg once daily (available as oral solution or tablet) 1
• Administer at approximately the same time each day, with or without food 1
• Tablets can be swallowed whole with water or dispersed in non-chlorinated drinking water 1
• If a dose is missed, administer within 6 hours; otherwise skip and resume regular schedule the next day 1

Expected Outcomes and Monitoring

Motor Function Improvements:

• 53.8-82% of adult patients achieve clinically meaningful improvement in at least one motor scale 2, 3
• Improvements typically occur in the Revised Upper Limb Module (RULM), Motor Function Measure-32 (MFM32), and Hammersmith Functional Motor Scale-Expanded (HFMSE) 4, 2
• Motor improvements are sustained over 24-30 months of treatment 4, 2
• MFM32 subdomain D3 (distal motor function) shows improvement in 66.6% of patients 4

Functional Improvements Beyond Motor Scales:

• All treated patients report subjective improvements in quality of life 5, 6
• Common patient-reported benefits include: improved breath fatigue, voice intelligibility, hand strength and dexterity, bulbar function, and digestion 4, 5, 6
• Weight gain occurs in approximately one-third of patients, with increased appetite reported 5

Tolerability Profile

Common Adverse Events (generally mild and transient):

• Skin photosensitivity/rash (most common) 6, 3
• Diarrhea 3
• Aphthous ulcers 3
• Abdominal pain 3
• 57% of patients report no adverse events 2
• Treatment discontinuation is rare; adverse effects typically decrease over time 4, 2

Monitoring Strategy

Baseline Assessment

• Motor function testing: RULM, HFMSE, MFM32 4, 2, 3
• Respiratory function tests 2, 6
• Quality of life measures (Individualized Neuromuscular Quality of Life questionnaire) 5
• Bulbar function assessment (Jaw Functional Limitation Scale if bulbar involvement) 5

Follow-up Schedule

• Motor function assessments at 6,12,18,24, and 30 months 2
• Respiratory function monitoring every 3 months 6
• Laboratory assessments for safety monitoring 2
• Patient-reported outcomes at each visit 5, 6

Special Considerations

Previously Treated Patients

• Patients previously treated with nusinersen who switched to risdiplam maintain pre-treatment motor scores 4
• Switching is appropriate if nusinersen was discontinued due to side effects or access issues 4

Treatment Response Timeline

• Type 3 patients typically achieve clinically meaningful improvement earlier than type 2 patients 2
• Improvements in bulbar function and subjective symptoms often precede measurable motor scale changes 4, 5
• Stabilization of motor function is a meaningful outcome in adult SMA, preventing expected decline 3

Critical Pitfalls to Avoid

Assessment Errors:

• Do not rely solely on HFMSE in adults, as it may fail to detect improvements captured by RULM or MFM32 4
• MFM32 is more sensitive than HFMSE for detecting treatment-induced changes in adult SMA type 3 4
• Always incorporate patient-reported outcomes, as subjective improvements may precede objective motor changes 5, 6

Drug Interactions:

• Avoid coadministration with drugs that are substrates of multidrug and toxin extrusion (MATE) transporters 1

Pregnancy Considerations:

• Based on animal data, risdiplam may cause fetal harm 1
• Discuss pregnancy-specific safety profile before initiating treatment in women of childbearing potential 1

Multidisciplinary Management

Essential Supportive Care:

• Physical therapy consultation for exercise prescription and periodic reassessment 7
• Respiratory monitoring and support as needed 2, 6
• Nutritional assessment, particularly given potential for weight changes 5
• Bulbar function monitoring and speech therapy if indicated 5

The systemic nature of risdiplam's mechanism requires monitoring beyond neuromuscular function, including gastrointestinal, respiratory, and bulbar systems. 5