What is the recommended treatment plan for an 11-year-old female patient with spinal muscular atrophy type 2 and sleep apnea, who is delayed on Spinraza (nusinersen) treatment due to insurance change and is also enrolled in a clinical trial for human anti-Promyostatin monoclonal antibody infusion?

Recommended Treatment Plan for 11-Year-Old with SMA Type 2

Continue Spinraza (nusinersen) 12mg intrathecal every 4 months as the established disease-modifying therapy, and proceed with the clinical trial anti-myostatin antibody (apitegromab) given the recent phase 3 evidence showing statistically significant motor function improvements when combined with nusinersen in nonambulatory SMA type 2 patients. 1

Primary Disease-Modifying Therapy: Spinraza Continuation

Rationale for Continuation

• Nusinersen is FDA-approved and has demonstrated safety and efficacy across all SMA types, with the most robust evidence supporting its use as foundational therapy 2
• The patient has been on established therapy with her last infusion delayed only due to insurance changes, not treatment failure or adverse effects 2
• Abrupt discontinuation of disease-modifying therapy in SMA is not recommended, as maintaining therapeutic levels is critical for preserving motor neuron function 2

Administration Considerations

• Critical concern: This patient has had spinal fusion surgery (noted in orthopedic follow-up), which creates technical challenges for intrathecal access 3, 4
• If standard lumbar puncture access is not feasible due to posterior fusion hardware, consider lumbar laminotomy between the lateral longitudinal rods below the conus level to create a surgical window for thecal access 4
• This laminotomy technique preserves mechanical stability and has been successfully used in multiple SMA patients with prior thoracolumbar fusions, with fluoroscopy times ranging 6-36 seconds and no postoperative complications 4
• Coordinate with interventional radiology or neurosurgery for intrathecal access planning given her spinal instrumentation 3, 4

Combination Therapy: Anti-Myostatin Antibody (Apitegromab)

Evidence Supporting Continuation

• The 2025 SAPPHIRE phase 3 trial demonstrated that apitegromab combined with nusinersen or risdiplam produced statistically significant improvements in motor function (least squares mean difference 1.8 points on HFMSE, p=0.019) in nonambulatory SMA type 2/3 patients aged 2-12 years 1
• The phase 2 TOPAZ study showed mean improvement of 0.6 points in HFMSE at 12 months in nonambulatory participants aged 5-21 years receiving apitegromab 20 mg/kg combined with nusinersen 5
• This patient fits the exact population studied: nonambulatory SMA type 2, age 11 years, receiving background nusinersen therapy 1, 5

Safety Profile

• Apitegromab demonstrated a well-tolerated safety profile with adverse events similar to placebo and consistent with SMA and background therapy 1
• Most common adverse events were pyrexia (26%), nasopharyngitis (25%), cough (23%), vomiting (23%), upper respiratory tract infection (22%), and headache (21%) 1
• No treatment discontinuations due to adverse events occurred in the phase 3 trial 1
• No deaths or serious adverse reactions were reported in the phase 2 study 5

Addressing the Noted Regression

• The clinical note indicates "unable to determine benefit due to regression in her repeat evaluation" with specific declines noted in left upper extremity function and overall motor scores 5
• However, this regression likely represents the natural disease course without adequate muscle-targeting therapy, as nusinersen alone addresses motor neuron survival but does not prevent muscle atrophy from preexisting neurodegeneration 5
• The combination approach with apitegromab specifically targets muscle preservation through myostatin inhibition, addressing the muscle component that nusinersen cannot fully restore 1, 5

Multidisciplinary Management Priorities

Physical Therapy Intensification

• Active, supervised physical therapy is strongly recommended throughout all disease stages and should be prioritized given her documented regression 6, 7
• The evaluation notes she is "not motivated to do any home exercise program," which contributes to weakness and contractures 6
• Focus on: passive stretching in prone position, knee extension stretches, trunk stabilization exercises, and active-assisted movements 6
• Address specific deficits: hip tightness, hamstring contractures, knee flexion contractures, and kyphotic posture 6

Sleep Apnea Management

• Continue monitoring for obstructive sleep apnea given her diagnosis and reports of increased morning sleepiness 6
• Most recent pulmonology evaluation (noted date) showed normal cough strength and mild condition, but new symptom of morning sleepiness warrants reassessment 6
• Consider repeat sleep study if symptoms progress, as OSA management is critical for quality of life in SMA patients 6

Nutritional Support

• Start vitamin D supplementation at 1000 international units daily as recommended in the assessment plan 6
• Monitor for metabolic complications given her age and disease progression 6

Monitoring Strategy

Motor Function Assessment

• Continue standardized motor function testing (HFMSE, RULM, WHO) every 6 months to objectively track response to combination therapy 1, 5
• The recent regression in scores (right side 28/26 improved, left side 21/25 declined) establishes baseline for comparison 5

Treatment Adherence

• Ensure Spinraza dosing returns to every 4-month schedule without further delays, as therapeutic gaps may contribute to functional decline 2
• Continue apitegromab infusions every 4 weeks as per trial protocol 1

Multidisciplinary Follow-up

• Maintain 6-month follow-up intervals with neurology, pulmonology, orthopedics, and physical therapy as currently scheduled 6, 7
• The planned multidisciplinary meeting is appropriate for coordinating care across specialties 7

Common Pitfalls to Avoid

• Do not discontinue nusinersen based on apparent plateau or regression, as this represents the natural disease course requiring muscle-targeted therapy augmentation 1, 5, 2
• Do not attempt intrathecal access without imaging review of her spinal fusion hardware; plan surgical access if needed before scheduling infusions 3, 4
• Do not attribute all functional decline to treatment failure; recognize that contractures, reduced therapy participation, and muscle atrophy from preexisting denervation contribute significantly 5
• Do not delay vitamin D supplementation, as bone health is critical in nonambulatory patients with limited weight-bearing 6