Soliris found effective as rescue therapy after kidney transplant in aHUS
But long-term outcomes for patients are poor, study results show
Soliris(eculizumab) was found to be effective in most patients with atypical hemolytic uremic syndrome (aHUS) when used as a rescue therapy for aHUS recurrence after a kidney transplant, according to a small study.
However, many patients also showed persistent kidney failure at the end of follow-up: three developed kidney failure, and three others had severe kidney insufficiency.
“Admittedly, although initial response to [Soliris] rescue therapy was considered good, long term outcome in our patients was not acceptable,” the researchers wrote.
The study, “Eculizumab Rescue Therapy in Patients with Recurrent Atypical Hemolytic Uremic Syndrome After Kidney Transplantation,” was published in the journal Kidney International Reports.
Investigating Soliris as a rescue therapy in aHUS
aHUS is a rare disorder characterized by the abnormal activation of part of the immune system known as the complement cascade. This triggers increased inflammation and blood clot formation in small blood vessels, particularly those in the kidneys.
It also is a type of thrombotic microangiopathy (TMA), a group of diseases marked by the formation of blood clots in the body’s small blood vessels, which leads to organ damage.
Soliris, developed by Alexion, which is now part of AstraZeneca, is approved to treat aHUS in the U.S., the European Union, and other locations. It is a complement inhibitor that acts by suppressing complement-mediated TMA symptoms.
In aHUS patients with advanced kidney disease, a kidney transplant may be necessary. For those who undergo the procedure, the optimal treatment strategy is up for debate.
A particular guideline-consensus statement recommends preventive or “prophylactic [Soliris] therapy in aHUS patients with an estimated moderate or high risk of recurrence, and lifelong continuation of therapy,” the researchers noted.
“However, this advice is not based on evidence from randomized clinical trials,” the team wrote.
In the Netherlands, kidney transplants in aHUS patients are usually performed in the absence of Soliris prophylaxis (preventive treatment). The medication is given, however, as a rescue therapy in case of disease recurrence after the procedure.
Now, researchers in the country have reported the outcomes of patients who received Soliris as rescue therapy for post-transplant aHUS recurrence. They also analyzed the disease recurrence rate among those who received a transplant in the absence of prophylactic treatment.
The study included 15 patients — 12 women and three men — with a median age of 42.
Researchers first observed that patients could be divided into two groups depending on the the time interval to disease recurrence. Seven patients showed signs of disease recurrence early on after the transplant — at a median of three months — while the other eight displayed them much later. For these eight patients, recurrence occurred a median of 46 months or nearly four years after the procedure.
For those with early disease recurrence, Soliris was started within one day after the detection of TMA signs in the blood, and 14 days after the last stable estimated glomerular filtration rate (eGFR) measurement. eGFR measures how well the small filter units in the kidneys — the glomeruli — are working to help remove waste and excess fluid from the blood.
In six of the seven patients, Soliris treatment led to TMA resolution and eGFR improvement.
When four patients stopped treatment, two continued to have a stable eGFR without evidence of disease relapse, while the other two experienced a relapse. However, re-introducing Soliris reverted relapse effects on eGFR, which slowly declined over time, “supporting underlying aHUS as cause of kidney function deterioration,” the researchers wrote.
Early vs later disease recurrence
In the case of patients who experienced disease recurrence later on, Soliris was started at zero to five days after TMA signs were detected in the blood. As in patients who experienced disease recurrence earlier, Soliris treatment in late recurrence patients led to TMA disappearance and eGFR amelioration.
Pregnancy, high blood pressure, and severe heart failure accompanied by influenza A infection were identified as possible triggers for aHUS recurrence in these patients.
Overall, Soliris treatment improved or stabilized kidney function in 14 of 15 patients. However, while discontinuation was attempted in seven, it was only successful in three. And 12 patients had poor long-term outcomes.
Admittedly, although initial response to [Soliris] rescue therapy was considered good, long term outcome in our patients was not acceptable.
At the end of follow-up, which was a median of 29 months (nearly 2.5 years) after therapy initiation, six patients had a low eGFR, indicating kidney insufficiency. The other three had graft or kidney function loss.
Finally, researchers also measured the aHUS recurrence rate without Soliris prophylaxis, which was reported to be at 23%.
“We cannot prove that a strategy of rescue therapy is noninferior to prophylactic therapy in patients with aHUS who receive a kidney transplant. However, our data suggest that rescue therapy is feasible, and able to maintain graft function in the majority of patients,” the researchers wrote.
The team also noted that “withdrawal of [Soliris] should be considered very cautiously, if at all.”
Overall, the study found that “rescue treatment of post-transplant aHUS recurrence is effective; however, some patients suffer from irreversible loss of kidney function.”
Researchers also noted that “physicians should be aware that recurrence of aHUS can present without evidence of systemic TMA.”