Eculizumab Brand Name– Soliris
What is Eculizumab
Eculizumab is a monoclonal antibody indicated for the treatment of paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), anti-acetylcholine receptor antibody positive generalized myasthenia gravis, and anti-aquaporin-4 (AQP4) antibody positive neuromyelitis optica spectrum disorder (NMOSD).
During clinical trials in patients with PNH, treatment with eculizumab has been shown to stabilize hemoglobin concentrations without blood transfusions, reduce the number of necessary blood transfusions, decrease LDH concentrations (a biochemical marker of hemolysis), decrease the number of PNH attacks, and improve quality of life including the symptom of fatigue.
Eculizumab (Soliris) is a humanized IgG2/4κ monoclonal antibody that binds C5 to inhibit its cleavage to C5a and C5b preventing the generation of the terminal complement complex, C5b-9.
It is approved for use to treat the complement-mediated thrombotic microangiopathy occurring in patients with atypical hemolytic uremic syndrome and to prevent the hemolysis that occurs in patients with paroxysmal nocturnal hemoglobinuria.
It also is used to treat generalized myasthenia gravis patients who are AchR antibody-positive.
Its most feared side effect is meningococcemia. Therefore, all patients should be immunized against meningococcemia and be on antibiotic prophylaxis during treatment. It costs $500,000 to $700,000 annually for therapy.
A reduction in blood transfusions and stabilization in hemoglobin concentrations have been demonstrated in patients receiving eculizumab for up to 64 weeks in duration.
In patients with aHUS, treatment with eculizumab prevents complement-mediated thrombotic microangiopathy (TMA). Three clinical studies have evaluated the safety and efficacy of eculizumab for the treatment of aHUS.
During these studies, patients receiving eculizumab experienced a reduction in terminal complement activity as indicated by increased mean platelet counts over baseline.
In a 26-week placebo-controlled trial of patients with generalized myasthenia gravis, patients receiving eculizumab had a greater improvement in the Myasthenia Gravis-Specific Activities of Daily Living scale from baseline to week 26.
Patients receiving eculizumab also reported a greater change from baseline to week 26 in the Quantitative Myasthenia Gravis score, a categorical scale assessing muscle weakness.
In a randomized, double-blind, placebo-controlled trial, eculizumab significantly reduced the time to relapse in patients with anti-AQP4 positive NMOSD, with a relative risk reduction of 94%.
There is an increased risk of meningococcal infections in patients receiving eculizumab; immunization with meningococcal vaccines is required prior to eculizumab administration unless the risks of delaying treatment outweigh the risks of developing a meningococcal infection.
Indications
- hemolytic-uremic syndrome
- myasthenia gravis
- neuromyelitis optica spectrum disorder
- paroxysmal nocturnal hemoglobinuria (PNH)
Side Effects
- abdominal pain
- alopecia
- anaphylactoid reactions
- anemia
- antibody formation
- arthralgia
- asthenia
- back pain
- cataracts
- conjunctivitis
- constipation
- cough
- cystitis
- diarrhea
- dizziness
- dyspepsia
- fatigue
- fever
- headache
- hemolytic-uremic syndrome
- hypertension
- hypokalemia
- hypotension
- infection
- influenza
- insomnia
- leukopenia
- lymphopenia
- meningitis
- meningococcal infection
- muscle cramps
- musculoskeletal pain
- myalgia
- nasal congestion
- nausea
- paresthesias
- peripheral edema
- pharyngitis
- proteinuria
- pruritus
- rash
- rhinitis
- shivering
- sinus tachycardia
- sinusitis
- thrombotic microangiopathy
- vomiting
Monitoring Parameters
- CBC with differential
- hemoglobin/hematocrit
- LDH
- neurologic function
- serum creatinine
Contraindications
- breast-feeding
- fungal infection
- immunosuppression
- infants
- infection
- meningococcal infection
- neonates
- neutropenia
- pregnancy
- streptococcal infection
Interactions
There are no drug interactions associated with Eculizumab products.
