What are the latest developments and evidence-based treatments for Amyotrophic Lateral Sclerosis (ALS)?

Latest Developments and Evidence-Based Treatments for ALS

The most significant recent development in ALS treatment is the FDA approval of edaravone (Radicava), which joins riluzole as the second disease-modifying therapy that can slow ALS progression, while multidisciplinary palliative care should be initiated from the time of diagnosis to improve quality of life and prolong survival. 1, 2

Disease-Modifying Treatments

Riluzole

• Remains the gold standard therapy for ALS 3
• Dosage: 100 mg/day (50 mg twice daily) shows the best benefit-to-risk ratio 4
• Survival benefit:
  • Clinical trials showed modest benefit in the months following treatment initiation
  • Real-world studies suggest more substantial benefit of 6-19 months extended survival 3
• Administration challenges:
  • Dysphagia (difficulty swallowing) can complicate medication intake
  • Alternative formulations now available:
    • Riluzole oral suspension (ROS) - can be used with PEG in severe dysphagia
    • Riluzole oral film (ROF) - requires minimal swallowing capacity 3

Edaravone (Radicava)

• Recently FDA-approved treatment to slow ALS progression 2
• Available as:
  • Intravenous formulation: 60 mg administered as two consecutive 30 mg IV infusions over 60 minutes
  • Oral formulation (Radicava ORS): 105 mg (5 mL)
• Key considerations:
  • Monitor for hypersensitivity reactions and anaphylaxis
  • Contains sodium bisulfite which may cause allergic reactions, particularly in those with asthma
  • Common adverse reactions: contusion (15%), gait disturbance (13%), headache (10%) 1

Evidence-Based Supportive Care

Nutritional Management

• For patients with muscular fatigue and prolonged meals:

  • Fractionate and enrich meals with energy or deficient nutrients
  • Recommend oral nutritional supplementation if weight loss progresses 5

• For moderate dysphagia:

  • Dietetic counseling to adapt food and liquid textures
  • Consider instrumental study of swallowing (VFS, FEES) to guide texture modifications
  • Implement postural maneuvers (especially chin-tuck posture) to protect airways during swallowing 5

• Percutaneous endoscopic gastrostomy (PEG):

  • Should be considered to stabilize weight and prolong survival
  • Evidence level: B 6

Respiratory Management

• Non-invasive ventilation (NIV):
  • Should be considered to treat respiratory insufficiency
  • Benefits:
    • Lengthens survival (Evidence level: B)
    • Slows decline of forced vital capacity (Evidence level: B)
    • May improve quality of life (Evidence level: C)
  • Early initiation may increase compliance (Evidence level: C)
  • Insufflation/exsufflation may help clear secretions (Evidence level: C) 6

Palliative Care Integration

Timing of Palliative Care

• A palliative care approach should be adopted from the time of diagnosis - not just in terminal stages 5
• Early referral allows time to establish relationships with staff and address end-of-life issues before communication becomes limited 5

Barriers to Optimal Palliative Care

• Management of terminal phase reported as unsatisfactory in 33% of cases in northern Europe and 61% in southern Europe
• In the UK, only 30% of palliative units provide ALS care, with only 8% involved from diagnosis
• In the US, stringent Medicare criteria limit hospice access 5

End-of-Life Discussions

• Optimal timing for end-of-life discussions includes:
  • Presence of patient distress
  • Evolution of disease
  • Patient's expressed desire to discuss these issues 5

Special Considerations for Cognitive Impairment

• Up to 50% of ALS patients may have some degree of cognitive impairment
• Patients with cognitive changes:
  • Are less likely to choose long-term mechanical ventilation
  • Show poorer compliance with NIV and feeding tubes
  • Are at higher risk for falls, choking episodes, and injuries
  • May require modified approaches similar to those used in advanced dementia 5

Quality of Life Assessment

• Several specialized tools available for QoL assessment in ALS:
  • Schedule for the Evaluation of Individualised Quality of Life (SEIQoL-DW)
  • Schedule for Meaning in Life Evaluation (SMiLE)
  • McGill QoL Questionnaire (MQoL) and ALS-specific QoL (ALSSQOL) 5

Multidisciplinary Approach

• Evidence shows multidisciplinary care improves both survival and quality of life in ALS
• Requires effective communication between:
  • ALS multidisciplinary team
  • Primary care physician
  • Palliative care team 5

Key Pitfalls to Avoid

• Delaying palliative care until terminal stages
• Failing to address cognitive impairment when planning interventions
• Overlooking rare but distressing symptoms (severe pain, frozen shoulder, mouth ulcers)
• Limiting availability of supportive treatments once formal palliative care begins
• Neglecting caregiver support and needs 5