Interval treatment with Soliris (eculizumab) may have a steady and prolonged effect in treating people with atypical hemolytic uremic syndrome (aHUS) with limited access to the costly drug, a case report suggests.
Further studies focused on defining the best dose and regimen are still required, researchers said.
The case was described in the study, “Three months interval therapy of Eculizumab in a patient with atypical hemolytic uremic syndrome with hybrid CFHR1/CFH gene,” published in the journal CEN Case Reports.
Soliris is a complement inhibitor discovered, developed, and marketed by Alexion. It works by blocking the signals of the immune system’s complement pathway that, when activated in an uncontrolled manner, contributes to the development of rare and serious diseases such as paroxysmal nocturnal hemoglobinuria (PNH), aHUS, and generalized myasthenia gravis (gMG).
aHUS is a rare progressive illness associated with high-risk permanent renal damage. It is caused by disregulation of the complement system — a set of more than 20 blood proteins that form part of the body’s immune defenses. About 60-70% of aHUS patients carry mutations in genes that encode those complement regulatory proteins.
Extra-renal manifestations occur in about 20% of patients. It most commonly involves the central nervous system, with altered consciousness, seizures, or focal neurologic deficits, and the gastrointestinal system, with diarrhea.
Researchers presented the case of a 26 year-old woman who developed pregnancy-associated aHUS.
She first developed acute kidney injury, thrombocytopenia (low levels of blood platelets), and microangiopathic hemolytic anemia (reduced levels of red blood cells due to their destruction) after having her child.
She had also experienced seizures and was diagnosed with posterior reversible encephalopathy syndrome (PRES) as a neurological complication of aHUS.
At that point she started hemodialysis as renal replacement therapy. She also started plasmapheresis to remove any potentially harmful antibodies from the body. After 10 sessions of plasmapheresis, she had significantly better levels of platelets and lactate dehydrogenase (LDH), but her kidney function remained impaired.
Analysis of kidney tissue revealed damaged blood vessels consistent with thrombotic microangiopathy (TMA), caused by clumps of platelets and broken red blood cells, and consequent tissue damage.
Twenty-two days after being admitted, she started treatment with intravenous Soliris. She underwent weekly infusions of 900 mg for four weeks, followed by 1,200 mg every two weeks. Upon the sixth treatment with Soliris, she experienced significant improvement in her renal function, and improvement in LDH and platelet levels.
Because of the high cost of Soliris therapy, she was unable to continue the treatment for six months, and returned to the hospital with recurrent aHUS. She again developed thrombocytopenia and slightly elevated blood creatinine, suggesting new renal involvement.
Genetic analysis did not reveal any common mutations that could help explain aHUS recurrence or reduced responsiveness to Soliris. Still, she had a rare genetic variant that led to the formation of a hybrid complement protein, in which part of the CFHR1 protein is replaced by part of the CFH protein.
Little is known about the impact of such CFHR1/CFH protein. However, some preliminary studies have suggested that it may affect the activation of complement pathways. “Thus, the detected CFHR1/CFH hybrid is most likely [disease-causing],” researchers said.
She restarted treatment with Soliris immediately and she again achieved full remission.
After financial mediation with her insurance company, she was approved to receive four 1,200-mg doses of Soliris per year. With this treatment regimen, she has been able to be in full remission for three years.
“The optimal duration of eculizumab treatment in aHUS and the decision to stop treatment remain under debate,” researchers said.
“Our approach has advantage over the traditional approach of stopping eculizumab and retreat in case of relapse. It is planned, cheaper, and less doses of [Soliris] required maintaining remission in comparison with induction doses in case of relapse,” they stated. “It protects patient against risk of tissue injury and loss of nephrons [functional units of the kidneys] associated with relapse.”
Despite the positive outcome in this case, the team highlights that increasing the interval between doses of Soliris should not be seen as a recommendation for patients with no issues with drug availability. Additional studies are warranted to explore the long-term effects and safety of this approach.