Soliris prevents an aHUS relapse after a kidney transplant, meta-analysis finds
Treated patients also less likely to need dialysis, reject transplanted organ
Relapses were less likely in people with atypical hemolytic uremic syndrome (aHUS) treated with Soliris (eculizumab) after a kidney transplant, and they had better kidney function and a lower risk of transplant rejection, according to a meta-analysis of published studies.
“This meta-analysis … demonstrated that [Soliris] produced meaningful efficacy in patients with AHUS after kidney transplantation,” its researchers wrote.
The report, “New findings in preventing recurrence and improving renal function in AHUS patients after renal transplantation treated with eculizumab: a systemic review and meta-analyses,” was published in Renal Failure.
Soliris is known to prevent relapses, but benefits with a transplant debated
In aHUS, abnormal activation of the complement cascade, a part of the immune system, leads to the formation of blood clots in small blood vessels, damaging internal organs, especially the kidneys.
While some patients will need a kidney transplant, this surgery often is not successful due to high aHUS relapse rates that cause additional damage.
Alexion’s Soliris is an antibody that binds to a complement protein called C5 to stop uncontrolled complement activation. Widely approved to treat aHUS patients, Soliris has proven effective at preventing disease relapses and improving kidney function, including after kidney transplant.
Still, the treatment is costly and has potentially serious side effects, including an elevated infection risk. Its potential benefits after a transplant also remain controversial, according to the team of scientists in China.
These researchers conducted a systematic review and meta-analysis of studies published between October 1970 and 12 February 2023 reporting on outcomes of Soliris’ use after a kidney transplant in adult aHUS patients.
A total of 18 studies, covering 618 patients and looking at various clinical outcomes (published between 2012 and 2022), were included. For each outcome of interest, the meta-analysis looked at the overall effect of Soliris across studies that included that outcome.
Results indicated that that use of Soliris after a transplant significantly lowered the risk of a disease relapse. It also significantly reduced the need for dialysis, a procedure to filter waste from the blood when the kidneys aren’t functioning.
Studies needed into timing of Soliris’ use in transplant patients
Soliris also was associated with improved kidney function. Specifically, the treatment significantly reduced blood creatinine levels — a marker of kidney dysfunction — and significantly increased glomerular filtration rate, which reflects the kidneys’ abilities to filter waste.
Lactate dehydrogenase, a marker of tissue damage, also decreased across studies measuring this factor. Platelets, which are involved in blood clotting and known to be depleted in aHUS, were significantly increased with Soliris.
Moreover, Soliris significantly reduced the likelihood of transplant rejection, which occurs when the body’s immune system recognizes the donor’s organ as foreign and attacks it.
Findings were generally consistent between studies with and without a control group that was not treated with Soliris.
Taken together, the findings indicate that Soliris “produced meaningful efficacy in patients with AHUS after kidney transplantation,” the researchers wrote.
Soliris given after a transplant “has good efficacy and safety and can prevent AHUS recurrence by improving renal function and blood normalization without causing rejection,” they added.
These studies’ results also might offer insights into the optimal use of Soliris, the team noted. Particularly, some of these studies, along with others, found that starting treatment prior to the transplant was better than waiting until after the procedure.
Evidence from studies not included in the meta-analysis also suggest that it may be safe to discontinue Soliris after achieving remission.
“The decision to discontinue [Soliris] is based on the patient’s risk factors, such as the patient’s [blood] parameters and [kidney] function levels,” the researchers wrote.
They also noted that while CFH gene mutations, known to affect the complement system, are linked to poorer outcomes after a kidney transplant, available data in this analysis were too limited to evaluate the role of genetics in Soliris responses.
“The potential influence of gene mutations cannot be ruled out,” the scientists wrote, adding that “future research should aim to explore the specific role of [Soliris] in the context of CFH gene disruption.”
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