Personalized Soliris Regimen Prevented Recurrence, Reduced Costs
Soliris (eculizumab) maintenance therapy administered every three weeks — instead of the biweekly standard regimen — was sufficient to normalize blood parameters and prevent disease recurrence for at least three years in a 4-year-old boy with atypical hemolytic uremic syndrome (aHUS), a case study reported.
Individualized Soliris dosing was based on its pharmacokinetics (uptake, distribution, and elimination in the body) in the boy, and researchers stressed their approach can be used to improve clinical outcomes, while reducing treatment burden and costs for aHUS patients.
The study, “Case Report: Atypical HUS Presenting With Acute Rhabdomyolysis Highlights the Need for Individualized Eculizumab Dosing,” was published in the journal Frontiers in Pediatrics.
Soliris, developed and marketed by Alexion, is a treatment for aHUS that specifically blocks the C5 protein, a component of the complement system — a part of the immune system chronically and highly activated in aHUS patients. By doing so, Soliris inhibits the development of blood clots, small blood vessel damage, and organ impairment — the hallmarks of aHUS.
The treatment is given intravenously (injected into a vein) and starts with an induction phase of once-weekly doses. This is followed by a maintenance dosing in which Soliris is given once every two weeks.
Standard maintenance dosing for aHUS children is weight-based. Children weighing less than 10 kilograms (about 22 pounds) are given 300 mg every three weeks, and then 300 mg every two weeks when they weigh between 10 and 20 kg (about 44 pounds). Patients weighing 40 kg (about 88 pounds) or more receive 1,200 mg of the medication every two weeks.
Dosing optimization is particularly important, since treatment is costly (more than $500,000 per year for a patient weighing 40 kg or more) and requires biweekly doses — possibly for a lifetime — representing a high economic and physical burden to aHUS patients and caregivers.
These facts “highlight the continued need and critical importance of optimizing therapeutic approaches in patients treated with eculizumab,” the researchers wrote.
Here, a team of researchers in Ohio described the case of a 4-year-old boy with aHUS and skeletal muscle involvement, whose disease was treated successfully with an individualized Soliris maintenance dosing lasting at least three years.
The previously healthy boy was diagnosed with aHUS two days after he was admitted to hospital. He received a weight-based induction dose of Soliris (600 mg) and was started on hemodialysis.
After the initial induction dose of Soliris, his platelets reached 126,000, but then dropped to 58,000 a few days later. He was given a second weight-based dose of 300 mg as his weight was 18 kg (about 40 pounds). After the second dose, platelets peaked to 146,000, but then decreased to 88,000 three days later. He received an extra dose of 300 mg and then was maintained on weekly doses of 600 mg.
Despite this, values rose and fell again and there were still two episodes of rhabdomyolysis — a life-threatening condition caused by breakdown and death of muscle fibers.
After a three-week period of hemodialysis, his platelets returned to normal values. Based on these results, the patient returned to the standard weight-based dosing of Soliris (600 mg every two weeks).
Enough Soliris trough levels were achieved (higher than 100 mcg/mL) and the patient had low or undetectable total complement activity (called CH50). Notably, trough levels are the lowest therapy levels before the next dose is given.
Researchers decided to apply personalized dosing to the patient based on pharmacokinetic parameters and his individual data. The patient’s pharmacokinetic simulation suggested he could be maintained safely on a three-week dosing regimen.
He was moved to this dosing regimen, with blood tests taken before each injection then spaced every three to four months. A three-year follow up has shown that Soliris levels were still sufficient, ranging from 120 to 280 mcg/mL, and CH50 levels were maintained constantly below the limit of detection, meaning that no disease recurrence occurred. These findings suggest that the individualized Soliris dosing was effective.
This standard maintenance dosing on a biweekly dosing in this patient has an estimated annual cost of $312,000. When the dosing interval was changed to every three weeks, costs dropped to $208,000, representing annual savings of $104,000.
According to researchers, “individualized weaning of eculizumab in the maintenance phase may be safely executed and provide significant cost savings.”
The cost of Soliris doses required to control aHUS during its acute phase was $72,000, a regimen researchers believe could have been more personalized through monitoring of CH50 and Soliris levels.
However, the “prevention of lifelong severe morbidity, including prolonged ICU stay and hospitalization, chronic kidney disease, dialysis, and renal transplant, far outweighs the cost of adequate early disease suppression,” they wrote.
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