Does a patient with generalized myasthenia gravis (gMG) meet medical necessity for initial therapy with Ultomiris (ravulizumab-cwvz)?

Medical Necessity Determination for Ultomiris (Ravulizumab-cwvz) Initial Therapy

Recommendation

This patient does NOT meet medical necessity criteria for initial therapy with Ultomiris (ravulizumab-cwvz) because the MG-ADL score of 1 fails to meet the required threshold of ≥5, despite meeting all other clinical criteria. 1

Detailed Analysis of Coverage Criteria

Criteria Met (4 of 5):

1. Anti-AChR Antibody Positive: ✓ Patient has documented AChR-positive, non-thymomatous myasthenia gravis 1

2. MGFA Clinical Classification II-IV: ✓ Patient is documented as MGFA Class IIB 2

3. Inadequate Response to Two Immunosuppressive Therapies: ✓ Patient has failed:

   • Vyvgart infusions (neonatal Fc receptor blocker) 2
   • Combination therapy with pyridostigmine, prednisone, and azathioprine over several months 2, 3
   • Required two hospitalizations with intubation and plasmapheresis in August 2025 4

4. No Concurrent Complement Inhibitor or Fc Receptor Blocker: ✓ Patient discontinued Vyvgart prior to Ultomiris initiation 1

Critical Criterion NOT Met:

MG-ADL Score ≥5: ✗ Current MG-ADL score is 1 (documented 9/17/2025) 1

Critical Issue: Post-Treatment Scoring

The fundamental problem is that the MG-ADL score of 1 was obtained AFTER the patient received inpatient Ultomiris on 9/2/2025, not before treatment initiation. 1 This creates several concerns:

• The FDA label for ravulizumab specifically indicates treatment for adults with generalized myasthenia gravis who are anti-AChR antibody-positive, with clinical trial enrollment requiring significant disease burden 1
• The patient is documented as being "in pharmacologic remission" on 9/17/2025 following Ultomiris initiation 2
• Coverage criteria require demonstrating medical necessity BEFORE treatment, not after therapeutic response 1

Clinical Context Supporting Need Despite Score

While the MG-ADL score doesn't meet criteria, the clinical severity is evident:

• Two myasthenic crises requiring intubation within one month (August 2025) 4
• Required plasmapheresis during hospitalizations, indicating severe, refractory disease 4
• Rapid symptom recurrence within one week after previous infusions 4
• Bulbar symptoms including speech slurring and ptosis 2, 3

The German Neurological Society guidelines define highly active disease requiring complement inhibitors as those with frequent exacerbations, need for rescue therapy, or inadequate response to standard immunosuppression 5. This patient clearly meets clinical criteria for highly active disease based on recent myasthenic crises 5.

Recommendation for Coverage Approval

To establish medical necessity, the following documentation is required:

1. Pre-treatment MG-ADL score from before the 9/2/2025 inpatient Ultomiris dose, ideally from the July 2025 timeframe when the patient reported severe flareup with speech slurring and eye closure 2, 5

2. Documentation of disease severity during the August 2025 hospitalizations, including MG-ADL or QMG scores prior to plasmapheresis and Ultomiris 5, 6

3. Clinical justification explaining that the current low score represents therapeutic response to the loading dose already administered, not baseline disease state 6, 7

Alternative Pathway

If pre-treatment MG-ADL ≥5 cannot be documented, consider:

• Appeal based on clinical severity: Two myasthenic crises requiring mechanical ventilation within 30 days represents life-threatening disease that clearly exceeds the intent of MG-ADL ≥5 threshold 4, 5
• Peer-to-peer review: Emphasize that MGFA Class IIB with recurrent crises requiring plasmapheresis and intubation represents more severe disease than many patients with higher MG-ADL scores 5

Safety Considerations Met

The patient has appropriately received:

• Meningococcal vaccination (serogroups A, C, W, Y, and B) in September 2025 1
• Penicillin V 500mg twice daily as antibiotic prophylaxis 1

These meet the FDA's REMS requirements for Ultomiris therapy 1.

Conclusion on Medical Necessity

The patient has severe, refractory, life-threatening generalized myasthenia gravis that clinically warrants complement inhibitor therapy based on recent myasthenic crises, but lacks the required pre-treatment MG-ADL score ≥5 to meet formulary medical necessity criteria. 1, 5 The current score of 1 reflects therapeutic response to already-administered Ultomiris, not baseline disease severity 6, 7. Documentation of pre-treatment disease severity scoring is essential for approval 1.