Switching from Soliris to Ultomiris is safe after kidney transplant
Study: Blood, kidney-related disease markers stayed stable after change
People with atypical hemolytic uremic syndrome (aHUS) who’ve had a kidney transplant can safely switch from Soliris (eculizumab) to Ultomiris (ravulizumab-cwvz) without risking a recurrence of the disease.
That’s according to a real-world study that also found that blood and kidney-related disease markers remained stable after the switch, and that no transplant rejections were reported.
This “real-world evidence of the successful transition from [Soliris] to [Ultomiris] in kidney transplant recipients with aHUS, in whom the disease can be particularly severe with a high chance of disease recurrence,” the study’s researchers wrote. The study, “Effectiveness and Safety of Switching to Ravulizumab From Eculizumab in Kidney Transplant Recipients With Atypical Hemolytic Uremic Syndrome: A Global aHUS Registry Analysis,” was published in Clinical Transplantation. It was funded by Alexion, AstraZeneca Rare Disease, which markets both therapies.
aHUS is a rare form of thrombotic microangiopathy (TMA), a group of diseases where blood clots form in the small blood vessels, damaging internal organs, especially the kidneys. In aHUS, a part of the immune system called the complement cascade becomes overactive, driving inflammation and blood clotting in small blood vessels. The disease typically arises in people who carry mutations in genes that regulate the complement system’s function.
Kidney impairment is a significant aHUS complication, with many patients progressing to kidney failure even after a kidney transplant. There’s also a high rate of TMA recurring after a transplant in aHUS patients who aren’t being treated with a complement inhibitor, particularly those carrying specific genetic mutations.
Soliris and its successor, Ultomiris, are antibody-based therapies approved for aHUS that are administered via intravenous infusions. Both inhibit complement activation by targeting the C5 complement protein. However, Soliris is administered every two weeks, whereas Ultomiris is given every four or eight weeks after the initial loading doses.
Effects of switching to Ultomiris
Current guidelines recommend preventive treatment with Soliris for aHUS patients with moderate or high risk of disease recurrence after a kidney transplant. Outcomes for transplant patients who’ve switched from Soliris to Ultomiris aren’t known, however, leading researchers to analyze data from patients enrolled in the Global aHUS Registry (NCT01522183) up to September 2024 to assess the real-world efficacy and safety of switching.
Overall, 38 patients (33 adults, five children) who received a kidney transplant before switching to Ultomiris were included in the safety analysis. Twenty-seven patients (median age, 35.8 at the start of Ultomiris treatment; 59.3% women) who’d received Ultomiris for at least three months and had taken up to a month from the time they stopped Soliris and started Ultomiris were included in the efficacy analysis.
The median duration of treatment with Soliris was 66.1 months. With Ultomiris, it was 24.1 months.
Seventeen of the 27 patients (63%) were tested for mutations in complement genes, with 51.9% carrying a disease-causing mutation. The CFH gene was the one most often affected (42.9%).
Before starting Ultomiris, 35 kidney transplants were recorded among the 27 patients. The median time from a transplant until starting Ultomiris was 66.5 months, or about 5.5 years. After patients started Ultomiris, there were no kidney transplants or signs of TMA. Also, there were no registries of kidney transplant rejections or kidney failure, and there was no need for dialysis, where waste and excess fluid is filtered from the blood when the kidneys no longer function properly.
Lab work showed key kidney function parameters, including estimated glomerular filtration rate and creatinine, were stable after switching. Also, no changes were detected in lactate dehydrogenase, a marker of red cell blood destruction, and platelet counts.
The safety analysis revealed 23 adverse events among 19 patients, with 10 having infections. Most were considered mild or moderate and there were no deaths associated with Ultomiris.
“Overall, patients demonstrated stable kidney function and there were no treatment-related [ adverse events], meningococcal infections, or deaths reported during treatment with [Ultomiris],” they wrote.
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