What is the recommended dosage of eculizumab (eculizumab) for the treatment of anti-AChR (acetylcholine receptor) positive myasthenia gravis?

Eculizumab Dosing for Anti-AChR Positive Myasthenia Gravis

The recommended eculizumab dosing regimen for anti-AChR positive generalized myasthenia gravis is 900 mg IV weekly for 4 consecutive weeks (weeks 1-4), followed by 1200 mg IV at week 5, then 1200 mg IV every 2 weeks for maintenance therapy. 1, 2

Standard Dosing Protocol

The FDA-approved dosing schedule follows a specific induction and maintenance pattern: 2

• Induction Phase: 900 mg IV infusion weekly for 4 consecutive weeks (weeks 1,2,3, and 4) 1, 2
• Transition Dose: 1200 mg IV infusion at week 5 1, 2
• Maintenance Phase: 1200 mg IV infusion every 2 weeks thereafter 1, 2

This regimen achieves steady-state serum concentrations by week 4 and maintains complete terminal complement inhibition throughout treatment. 3

Pharmacokinetic and Pharmacodynamic Considerations

Therapeutic drug levels are rapidly achieved and sustained with this dosing regimen: 3

• Steady-state is reached by week 4 with approximately 2-fold accumulation 2
• At week 26, mean trough concentrations are 341 ± 172 mcg/mL and peak concentrations are 783 ± 288 mcg/mL 2
• Serum eculizumab concentrations ≥116 mcg/mL achieve free C5 concentrations <0.5 mcg/mL, which correlates with complete blockade of terminal complement activity 2, 3
• Complete inhibition of terminal complement is achieved in 92% of patients at trough concentrations and 87% demonstrate <20% in vitro hemolysis 3

Adolescent Dosing Modifications

For adolescent patients aged 12-17 years with refractory anti-AChR positive gMG, weight-based dosing adjustments apply: 4

• Induction: Either 1-2 doses of 600 mg weekly OR 4 doses of 900 mg weekly 4
• Maintenance: 300-1200 mg every 2 weeks based on body weight 4

Critical Pre-Treatment Safety Requirements

Meningococcal vaccination is mandatory at least 2 weeks before initiating eculizumab therapy: 1

• Administer both quadrivalent meningococcal A, C, W, Y conjugate vaccine (Menveo) AND meningococcal B vaccine (Bexsero or Trumenba) 1
• If treatment cannot be delayed for vaccination, initiate antimicrobial prophylaxis immediately with penicillin or macrolides (such as ciprofloxacin) and continue throughout treatment 1
• Monitor continuously for signs of meningococcal infection including fever, headache, neck stiffness, confusion, or flu-like symptoms 1

Dosing Adjustments for Plasma Exchange

Supplemental dosing is required when patients undergo plasma exchange or plasma infusion: 2

• Plasma exchange increases eculizumab clearance by approximately 250-fold and reduces half-life from 270-414 hours to 1.26 hours 2
• Administer supplemental doses according to the timing of plasma exchange procedures 2

Clinical Efficacy Evidence

Real-world and clinical trial data demonstrate the effectiveness of this dosing regimen: 5, 6

• Clinically meaningful reductions in MG-ADL scores are observed at 3 months and maintained through 12 months 5
• All patients in real-world studies achieved 'none' or 'mild' ratings for QMG evaluations after 12 months 5
• Acute exacerbations are significantly reduced, and concomitant medication requirements decrease substantially 5
• The regimen is well-tolerated with consistent efficacy across the eculizumab exposure range 6, 3

Important Clinical Pitfalls

Never delay meningococcal vaccination—this is the most critical safety measure and failure to vaccinate can result in life-threatening meningococcal sepsis. 1

• Do not deviate from the standard dosing schedule without pharmacokinetic monitoring, as subtherapeutic levels may result in incomplete complement inhibition 3
• Remember that eculizumab half-life is approximately 270-414 hours, so missed doses can lead to prolonged periods of inadequate complement blockade 2
• Ensure patients understand to immediately report fever, headache, or flu-like symptoms as potential meningococcal infection 1