Taking Soliris Less Often Is Effective and Can Save Money for US Patients, Study Says
Extended-dosing regimen can save patients at least $78K for a half-year treatment
Maintenance treatment with Soliris (eculizumab) every three to six weeks — instead of the standard two weeks — is sufficient to promote complement inhibition and disease remission in most adults with atypical hemolytic uremic syndrome (aHUS), a small study suggests.
This extended-dosing regimen is linked to savings of at least $78,000 per patient for a six-month treatment course.
These findings highlight that close monitoring of blood levels of Soliris and complement inhibition “allows for safe modification of [Soliris] dosing and results in considerable cost savings,” the researchers wrote.
However, larger studies are required to confirm these preliminary findings.
The study, “Clinical Utility and Potential Cost Savings of Pharmacologic Monitoring of Eculizumab for Complement-Mediated Thrombotic Microangiopathy,” was published in the journal Mayo Clinic Proceedings.
Soliris is designed to bind to C5 protein in the complement system
aHUS is a rare disorder characterized by the progressive destruction of red blood cells due to overactivation of the complement system — a set of more than 50 proteins that forms part of the body’s immune defenses.
Soliris, by Alexion Pharmaceuticals, is a monoclonal antibody that binds to C5, a protein of the complement system, thereby preventing its overactivation. Administered directly into the bloodstream, the treatment is designed to ease aHUS symptoms.
The standard dosing regimen for adults is four weekly infusions of 900 milligrams (mg) — the induction phase — followed by infusions of 1,200 mg every two weeks (maintenance phase).
… less frequent infusion visits … has the potential to impact the quality of life and result in significant cost savings
However, previous data suggested that complement activity in aHUS could be effectively suppressed with blood Soliris levels as low as 50 micrograms per milliliter (ug/mL).
To evaluate this further, researchers at the Mayo Clinic in Rochester, Minnesota, monitored Soliris levels and C5 activity in 10 aHUS patients (ages 22–68 years) to see whether the dosing interval could be extended without affecting efficacy.
For patients with C5 levels below 29 units/mL and Soliris levels higher than 100 ug/mL before the second maintenance dose, the researchers would reduce the frequency of subsequent Soliris doses by one-week increments.
The 100 μg/mL Soliris threshold “was chosen because at this concentration C5 is consistently either undetectable or below RI [reference interval],” the team wrote.
Results showed that blood concentrations of Soliris in patients ranged from 46 to 518 ug/mL. In all but one patient, the levels of Soliris were above 100 ug/mL and those of C5 were below the RI.
Anomaly in results found in obese patient
The one patient with subtherapeutic Soliris levels was a 26-year-old woman who weighed 127 kg or 280 lbs and was the heaviest of the included patients. This, together with the absence of weight-based doses of Soliris, may explain why she was the only one failing to achieve the therapeutic threshold of Soliris, the team noted.
Eight patients (80%) showed both Soliris levels above 100 ug/mL and C5 levels below 29 units/mL, and therefore fulfilled the criteria for an extended dosing regimen.
At the last follow-up of these patients (median of 250 days, or about eight months), Soliris interval dosing was extended to three weeks in three patients, to four weeks in one patient, to five weeks in three patients, and to six weeks in one patient. During this period, no aHUS relapses were observed.
“Most patients do not require [Soliris] doses of 1,200 mg … every 2 weeks to achieve adequate C5 inhibition,” the researchers wrote, adding that “this means less frequent infusion visits, which has the potential to impact the quality of life and result in significant cost savings.”
The estimated total cost savings for a six-month Soliris treatment course, with maintenance doses every three to four weeks, ranged from $78,165 to $130,596 per patient, the team noted.
Among the nine patients with at least two months of follow-up, eight discontinued Soliris after presenting no signs of aHUS-associated blood or kidney abnormalities.
After a mean follow-up of 227 days (about 7.5 months) post-remission, two patients experienced disease relapse and re-started Soliris, with both eventually reaching remission.
One patient chose to remain on Soliris (currently receiving treatment every three to five weeks), and the other switched to Ultomiris (ravulizumab-cwvz), Alexion’s successor to Soliris, which is administered at weight-based doses every eight weeks.
Overall, “our data suggest that monitoring of [Soliris] levels in conjunction with C5 allows for safe modification of [Soliris] dosing and provides significant cost savings,” the researchers wrote.
However, larger studies “are necessary to confirm these findings,” they concluded.