The study, “Eculizumab Safety: 5-Year Experience from the Global aHUS Registry,” was published in the journal Kidney International Reports.
Soliris, an engineered monoclonal antibody developed and marketed by Alexion, works by specifically targeting a component (protein C5) of the complement system — a part of the immune system chronically and uncontrollably activated in aHUS patients.
Soliris has been approved for the treatment of aHUS in 49 countries, including the United States, Japan, and several in Europe. Currently recommended as a first-line treatment for aHUS, the medicine is administered directly into the bloodstream, and it involves a first induction phase followed by lifetime maintenance in biweekly doses.
While previous studies have shown the safety and efficacy of Soliris in both adult and pediatric patients with aHUS, the long-term safety of Soliris in a large patient population and in a real-world setting remains uncharacterized.
Researchers evaluated the long-term safety of Soliris using the Global aHUS Registry database (NCT01522183), a worldwide retrospective-prospective registry aiming to study the natural history of aHUS, and the post-approval (post-marketing) long-term safety and efficacy of Soliris.
The study analyzed the medical data, adverse events, and mortality rates of 1,321 aHUS patients (842 adult and 479 pediatric) during the first five years of the registry and compared it with those who had ever or never received Soliris treatment.
Patients were included in the ever-treated group if they received at least one dose of Soliris before, during, or after enrollment.
Reported adverse events were focused on meningococcal infections, serious infections, sepsis (a potentially life-threatening condition caused by the body’s response to an infection), cancer, liver problems, and reactions to treatment’s intravenous administration.
With a cutoff of Jan. 26, 2017, 535 (63.5%) adults were ever treated with Soliris and 307 (36.5%) had never received the treatment. Among pediatric patients, 330 (68.9%) and 149 (31.1%) were ever or never treated with Soliris, respectively.
The mean duration of Soliris treatment was 2.17 years for adults and 2.72 for pediatric patients.
The baseline data of all the patients suggested that the only significant difference between the ever-treated and never-treated groups was disease severity, which was found to be more severe in patients who had ever been treated with Soliris. This may suggest a link between disease severity and the physician’s choice to prescribe Soliris to a patient.
Regarding safety, the most frequently reported adverse events among aHUS patients, regardless of Soliris treatment status, were serious infections and sepsis. No differences in adverse event rates were found between the ever-treated and never-treated groups of patients, except for serious infections in pediatric patients, which were higher for those who had received Soliris treatment.
The mortality rate was higher in patients never treated with Soliris (9.9%) compared with those in the ever-treated group (4.7%). Causes of death in both groups included sepsis/infections, cardiovascular disease, and cancer.
Results also showed that adult patients had higher mortality rates than pediatric patients. Meningococcal infections were reported in three patients (two adults and one pediatric) ever treated with Soliris; one of those infections led to a fatal outcome in an adult patient.
“The results of our analysis confirm the safety profile of [Soliris] previously established in the clinical trial setting and, therefore, a positive benefit-risk profile in a real-world setting,” the researchers said.