Soliris Helps to Protect Kidney Transplants in aHUS Patients – Provided Disease Diagnosed, Study Reports

Soliris (eculizumab), started before or just after a kidney transplant, works against graft loss and improves long-term kidney function — potentially avoiding dialysis — in people with atypical hemolytic uremic syndrome (aHUS) who were diagnosed before this surgery, a registry study reports.

But people not diagnosed with aHUS until after a transplant remain at high risk of requiring dialysis or having their kidney fail again, regardless of Soliris treatment. Researchers said these results call attention to, and strengthen, the importance of diagnosing aHUS and starting appropriate treatment early.

The study “Eculizumab Use for Kidney Transplantation in Patients With a Diagnosis of Atypical Hemolytic Uremic Syndrome”, was published in the journal Kidney International Reports.

Atypical hemolytic uremic syndrome (aHUS) often leads to advanced chronic kidney disease.

A kidney transplant was not recommended for these patients — advised again, in fact — because aHUS can re-emerge in the donated kidney, requiring dialysis and risking transplant failure.

But with the availability of Soliris (by Alexion) — a monoclonal antibody that targets the complement, a part of the immune system uncontrollably activated in aHUS — some studies suggest its use may improve the success of a kidney transplant.

An earlier grouped analysis of past clinical trials indicated that Soliris is beneficial when given shortly after a kidney transplant, working to improve kidney function and prevent graft rejection.

But information is limited “to guide clinicians as to the timing of eculizumab therapy in relation to transplantation, ” the research team noted in the study. 

Potential benefits of its use before and after the transplant has yet to be studied using adequate follow-up periods, the scientists added, noting their work focused on post-transplant advantages of pre-transplant treatment.

Their observational study analyzed outcomes in 188 aHUS patients who underwent kidney transplant, were treated with Soliris and followed for at least one year after the surgery.

All were part of the Global aHUS Registry (NCT01522183), a worldwide registry aiming to capture post-approval (post-marketing) safety data on Soliris’ use. This registry contains the largest database of transplant patients treated with Soliris, apart from any interventional clinical study.

Two groups of aHUS patients were compared: those receiving Soliris up to or at the time of their transplant (88 patients), and those who started treatment after the transplant (100 patients).

Of those starting Soliris post-transplant, 52 were diagnosed with aHUS before the surgery, and 48 only after their most recent kidney transplant. (Some had one or more prior transplants; median age of all patients was 34.1.)

Results in this group showed that graft loss — the loss of function in the transplanted kidney — occurred in 27 of these 100 people. Graft loss is defined as the need for consecutive dialysis over more than three months.

Three started with Soliris before or at time of the transplant (3%), and 24 initiated Soliris after the procedure — seven (13%) diagnosed with aHUS before and 17 (35%) who were diagnosed after the most recent transplant.

Within five years post-transplant, 47 patients in total required dialysis at least once.

Those more likely to end up requiring dialysis were patients given Soliris only after the transplant, and especially those diagnosed with aHUS after their most recent transplant.

Graft loss was also more likely to occur in this latter group of patients.

Measures taken six months’ post-surgery of the kidney’s glomerular filtration rate, used to assess how well the organ is working, showed significantly better function in the grafted kidney of patients who have started Soliris before or at the time transplant, compared with the other groups. This tendency was maintained over two years of follow-up.

Few safety concerns were reported. One patient had a meningococcal infection, which resolved with antibiotics, and three died due to causes unrelated to Soliris.

These findings “suggest eculizumab is beneficial for the treatment of patients with aHUS in the setting of transplantation, and carries a minimal risk of infection,” the researchers wrote.

“Compared with historical results, the current analysis showed favorable outcomes in transplanted patients with aHUS receiving eculizumab, with graft survival … improved compared with that reported in the literature” they added.

The data also support that Soliris started before a kidney transplant “potentially reduces rates of dialysis after transplantation,” requiring aHUS be diagnosed earlier.

Overall, these data agrees with current guidelines suggesting that aHUS diagnosis should be done as early as possible to initiate appropriate treatment timely.

Those not given an aHUS  diagnosis until after the transplant are at higher risk of graft failure, “emphasizing the importance of the timing of diagnosis of aHUS with respect to transplantation.”

“[A]ny transplant candidate with a clinical history or renal biopsy suggestive of thrombotic microangiopathy should be carefully evaluated for a possible diagnosis of aHUS and that treatment with eculizumab beginning at the time of transplantation will improve posttransplant outcome,” the researchers concluded.