What is the recommended first‑line Soliris (eculizumab) therapy regimen, vaccination requirements, monitoring schedule, and management of breakthrough hemolysis for patients with paroxysmal nocturnal hemoglobinuria (PNH)?

Eculizumab (Soliris) for Paroxysmal Nocturnal Hemoglobinuria

First-Line Dosing Regimen

Administer eculizumab 900 mg IV weekly for 4 consecutive weeks (weeks 1-4), followed by 1,200 mg IV at week 5, then 1,200 mg IV every 2 weeks for maintenance therapy. 1, 2

• The original FDA approval studies used 600 mg weekly for 4 weeks, then 900 mg at week 5, followed by 900 mg every 2 weeks 3, 4, 5, but current guidelines recommend the higher maintenance dose of 1,200 mg every 2 weeks 1, 2

Mandatory Pre-Treatment Vaccination Requirements

Meningococcal vaccination must be completed at least 2 weeks before initiating eculizumab therapy, as terminal complement blockade dramatically increases risk of invasive meningococcal disease. 1, 2, 6

Specific Vaccine Requirements:

• Administer both quadrivalent meningococcal conjugate vaccine (A, C, W, Y) AND meningococcal B vaccine (Bexsero or Trumenba) 1, 2
• If treatment cannot be delayed for the 2-week vaccination period, initiate antimicrobial prophylaxis immediately with penicillin or macrolides (such as ciprofloxacin) and continue throughout eculizumab treatment 1, 2
• Maintain long-term antimicrobial prophylaxis with penicillin (or macrolides for penicillin-allergic patients) for the entire duration of treatment 1

Critical Safety Monitoring:

• Monitor continuously for signs of meningococcal infection including fever, headache, neck stiffness, confusion, or flu-like symptoms 2
• Evaluate and treat immediately with antibiotics if any signs of meningococcal infection develop 2

Monitoring Schedule

Baseline Assessment:

• Flow cytometry to quantify GPI-negative cells in neutrophils and red blood cells (gold standard for PNH diagnosis) 7
• Complete blood count with peripheral smear showing evidence of hemolysis 7
• Hemolysis markers: LDH, haptoglobin, indirect bilirubin, reticulocyte count 1, 7
• Direct antibody test (Coombs) to exclude autoimmune hemolytic anemia 7
• Renal function tests and urinalysis for hemoglobinuria 7
• Complement testing (C3, C4, CH50) 7

Ongoing Monitoring During Treatment:

• Monitor hemoglobin and reticulocyte count regularly to assess treatment response 1, 7
• Track LDH, haptoglobin, and indirect bilirubin as markers of hemolysis 1
• Surveillance for breakthrough hemolysis symptoms: dark urine, fatigue, abdominal pain 1, 7
• If extending the interval of C5 inhibitor administration, monitor C3, C4, CH50, and AP50 1

Management of Breakthrough Hemolysis

Breakthrough hemolysis can occur despite eculizumab therapy due to extravascular hemolysis of C3b-opsonized red blood cells, which eculizumab does not prevent.

Supportive Management:

• Administer RBC transfusions only to relieve symptoms or achieve hemoglobin 7-8 g/dL in stable, non-cardiac patients 2, 7
• Use extended antigen-matched red cells (C/c, E/e, K, Jk^a^/Jk^b^, Fy^a^/Fy^b^, S/s) when feasible to prevent alloimmunization 2
• Provide folic acid supplementation 1 mg daily to support erythropoiesis 7
• Iron supplementation (oral or IV) may be needed for iron deficiency from chronic hemoglobinuria 7

Thrombosis Management:

• Anticoagulation is recommended for patients with prior thrombotic events, as thrombosis risk persists even on eculizumab 7
• Hematology consultation is recommended for patients with severe hemolysis or thrombosis 7

Critical Pitfalls and Caveats

Never Delay Vaccination:

• This is the most critical safety measure—failure to vaccinate increases risk of life-threatening meningococcal sepsis 2
• Patients must be monitored continuously for infection signs throughout treatment 2

Screen for Genetic Resistance:

• Patients of Chinese and/or Japanese descent may not respond to C5 inhibitors due to polymorphic variants of the C5 gene, which leads to resistance to anti-C5 monoclonal antibodies 1
• Screen for Chinese/Japanese ancestry before initiating therapy 1

Maintain Prophylaxis:

• Antimicrobial prophylaxis must continue throughout the entire treatment duration, not just the initial period 1, 2

Expected Clinical Response:

• Eculizumab reduces intravascular hemolysis by approximately 87% as measured by LDH reduction 3
• Transfusion requirements decrease by approximately 52%, with 51% of patients achieving complete transfusion independence 3
• Hemoglobin stabilization occurs in approximately 49% of patients 4
• Fatigue scores improve significantly, with mean improvement of 12.2 points on FACIT-Fatigue instrument 3