Soliris (eculizumab) safely and effectively treated a severe episode of atypical hemolytic uremic syndrome (aHUS) in an adolescent with another autoimmune disease called systemic lupus erythematosus (SLE), a case report described.
The therapy’s use was also safely discontinued, without an aHUS relapse.
The case study, “Successful Discontinuation of Eculizumab in a Pediatric Patient With Atypical Hemolytic Uremic Syndrome and Underlying Systematic Lupus Erythematosus,” was published in the journal Cureus.
In people with SLE, self-reacting antibodies against double-stranded DNA (dsDNA), among other molecules, can cause damaging deposits in the kidneys. This leads to lupus nephritis, a common SLE complication characterized by kidney inflammation that ultimately can result in kidney failure.
SLE, like aHUS, is also marked by overactivation of the complement system, a part of the immune system involved in fighting infections. aHUS is a form of thrombotic microangiopathy (TMA), a group of rare, severe diseases characterized by red blood cell destruction, low platelet counts, and the formation of blood clots in small blood vessels that can lead to organ damage, most commonly affecting the kidneys.
‘Dramatic improvement’ follows Soliris’ use
aHUS is often treated with Soliris, by Alexion Pharmaceuticals, a complement-suppressing therapy shown to effectively prevent kidney failure. However, optimal treatment duration is still unclear, as well as whether it “can be successfully discontinued without TMA reoccurrence,” the researchers wrote.
A team at the University of Iowa described the case of an 18-year-old boy with SLE complicated by a severe aHUS episode that was effectively resolved with Soliris, given weekly for one month and biweekly for another three months. The treatment was then stopped without aHUS recurrence.
The teenager, who had a developmental disorder due to a genetic defect, came to their hospital after six months of weight loss, fatigue, and recurrent fever. His kidney function was normal in previous tests.
He tested positive for anti-dsDNA antibodies and showed abnormal levels of certain complement proteins, supporting a diagnosis of SLE.
Two months later, he developed an acute kidney injury, confirmed by elevated creatinine levels and increased protein in his urine. This was accompanied by accelerated destruction of red blood cells and low platelet counts, along with seizures and reduced alertness.
A kidney biopsy showed advanced lupus nephritis and severe lupus vasculopathy, characterized by blood vessel inflammation and destruction, along with signs of TMA.
Notably, genetic testing for variants previously associated with TMA came back negative.
The teenager received five doses of two immunosuppressive therapies — methylprednisolone and cyclophosphamide (sold as Cytoxan, among other brand names) — both delivered directly into the bloodstream.
His kidney function continued to decline, and a second kidney biopsy two weeks later revealed severe kidney damage. He then underwent five sessions of plasma exchange over the span of one week. Plasma exchange involves removing and replacing a person’s plasma — the liquid portion of blood that contains water, salts, and proteins. In the case of aHUS, it is used to replace defective or deficient complement control proteins.
Solaris was started as his condition continued to worsen, despite three weeks of immunosuppressive treatment. Its use “resulted in a dramatic improvement of his clinical course,” the researchers wrote.
Within two weeks of initiating Soliris, better kidney function was evident, as assessed through creatinine levels and the estimated glomerular filtration rate. Trends towards normalization were also seen in the levels of certain complement proteins, platelets, and hemoglobin, the protein in red blood cells that is responsible for the transport of oxygen.
“Because of his improved condition, the [Soliris] regimen was discontinued and he continued a maintenance therapy consisting of daily mycophenolate mofetil, prednisone, and hydroxychloroquine for SLE,” the scientists wrote.
“Further supporting this decision was his negative genetic panel which indicated the overactivation of the alternative complement pathway associated with aHUS was unlikely to be the result of permanent genetic factors making his aHUS would not be a reoccurring issue,” they added.
Indeed, lab tests indicated better kidney function in the months following Soliris discontinuation, with no aHUS relapse reported over the year following the initial episode.
Potential for yet-unknown aHUS genetic risk
Overall, this case suggests Soliris “can successfully be discontinued without aHUS relapse in a pediatric patient with underlying SLE given laboratory markers indicating adequate kidney function, stable SLE, and no apparent genetic causes for the aHUS event,” the team wrote.
This and a previous case of aHUS in an SLE patient who was also negative for TMA-associated genetic risk factors suggest “there could be another gene or autoantibody associated with SLE contributing to these patients’ increased risk for aHUS development,” they added.
“A multi-center study would be helpful in capturing more of these rare cases and clarifying the mechanism of how SLE can trigger aHUS and increase relapse risk, especially in patients with negative genetic results,” the scientists concluded.