Soliris Is Safe and Effective in Real-world Use, Small US Study Shows
Soliris (eculizumab) safely and rapidly led to clinical benefits in people with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor antibody positive, according to data from a small real-world U.S. study.
Moreover, most patients discontinued maintenance immunomodulatory treatment.
The study, “Safety and outcomes of eculizumab for acetylcholine receptor-positive generalized myasthenia gravis in clinical practice,” was published in Muscle & Nerve.
Soliris, developed by Alexion Pharmaceuticals, is approved in the U.S., Europe, and Japan to treat people with gMG positive for self-reactive antibodies against acetylcholine receptors (AChR), the most common type of MG-causing antibody.
Its approval was based on safety and effectiveness data of adults with gMG who enrolled in the six-month, placebo-controlled Phase 3 REGAIN trial (NCT01997229) and its four-year, open-label extension study (NCT02301624).
In both trials, Soliris resulted in clinically meaningful benefits in patients who failed to respond to other immunosuppressive therapies. These included boosting muscle strength, activities of daily living, functional ability, and quality of life. Evidence of real-world data has been limited, however.
A team of researchers examined the medical records of 12 adults with gMG who were positive for AChR antibodies (mean age 57.4 years; six women) and were followed at the Brigham and Women’s Hospital and at the Massachusetts General Hospital, both in Boston.
They had received at least one dose of Soliris and were followed for a mean of 18 months (range 2–21.6 months). Patients were previously treated with a mean of 3.2 immunomodulatory therapies, but the majority (eight) had refractory MG, meaning they failed to respond to prior treatments.
Four had a clinical history of a rare tumor in the thymus gland, commonly known as a thymoma, and underwent a thymectomy. Patients had been vaccinated against bacteria responsible for meningitis at least 14 days before starting Soliris.
At the time they started Soliris, most patients were on standard therapies, including pyridostigmine (sold as Mestinon, among other brand names), prednisone, and a nonsteroidal immunomodulatory therapy. Maintenance therapy with intravenous immunoglobin (IVIG) or plasma exchange was followed by seven patients.
Researchers evaluated the effects of treatment on MG Foundation of America Post-intervention Status (MGFA-PIS), which measures changes in MG clinical signs after treatment. Treatment effects on clinical classification (MGFA-CC) and MG-Activities of Daily Living (MG-ADL), as well as the need for additional immunomodulatory therapies, and adverse events, were also evaluated.
Results showed patients saw rapid clinical improvements, with gains in MGFA-PIS scores and MGFA-CC scores seen in at least 80% after a month.
Patients’ ability to do daily living activities, as measured by MG-ADL, showed that its scores — with higher scores indicating more disability — decreased from a mean of 8.7 to 2.8 after one month.
The scores remained 3.5 or lower for more than 1.5 years and, during this period, the mean dose of prednisone dropped from 22.5 to 7.2 mg. Prednisone dose reduction occurred in nine of the 10 prednisone-treated patients, but none fully discontinued the therapy.
The five patients on IVIG maintenance therapy discontinued it upon starting Soliris. However, in two cases, maintenance therapy was re-introduced after one year due to limited clinical improvement. The other two patients who underwent plasma exchange therapy discontinued it after one and six months, without clinical worsening.
There were no reports of infections by meningitis-causing bacteria and side effects were mild, without any leading to discontinuing Soliris.
Most patients saw “clinical improvement … after eculizumab initiation, beginning as quickly as 1 month,” the researchers wrote, noting that, compared with REGAIN, more patients reduced their steroid dose, but couldn’t taper off of it. Tapering of oral immunosuppressants was rare, they added.
Although REGAIN excluded patients with a history of thymoma, findings from this study support the benefits of Soliris in these patients.
“This study helps provide realistic expectations of change in MG symptoms with eculizumab in clinical practice,” the researchers wrote.