Soliris (eculizumab) rapidly improved renal function that had been compromised by clotting of small blood vessels in patients with atypical hemolytic uremic syndrome (aHUS), researchers report.
The study with that finding, “Outcomes in patients with atypical hemolytic uremic syndrome treated with eculizumab in a long-term observational study,” was published recently in BMC Nephrology.
aHUS leads to the formation of blood clots in the blood vessels, which ends up blocking regular blood flow to the kidneys, brain and heart, compromising their function.
Soliris is an approved antibody therapy that prevents or reduces small blood vessel destruction and the formation of blood clots, reducing symptoms and organ damage in aHUS. However, the optimal duration of treatment with this drug has not been established.
There is growing, but limited, information on the long-term clinical status of aHUS patients who previously received or are continuing to receive treatment with Soliris.
Investigators designed an observational, multi-center, multi-national, long-term follow-up study (NCT01522170) of aHUS patients who had been treated with Soliris in prior studies. The study allowed researchers to understand the effects of long-term therapy in the patients’ clinical status.
The primary goal was to assess the rates of thrombotic microangiopathy (TMA) events — the formation of blood clots due to injury of small blood vessels — while off, and while on, Soliris. Scientists also evaluated the patients’ kidney function and treatment side effects.
Of 93 patients (26 children/adolescents, 67 adults; aged 0 to 80 years), 51 (55%; 22 children/adolescents, 29 adults) remained on Soliris and 42 (45%; 17 children/adolescents, 25 adults) had at least one off-treatment period.
For those who discontinued therapy, 21 (50%) restarted treatment because they had TMA, renal impairment, multiple serious adverse events, had to change their dosing regimen, or prepare for a kidney transplant.
Patients who restarted Soliris were more likely to have immune system-related genetic/autoimmune abnormalities, formed more blood clots prior to treatment, and had longer disease course, in comparison to the ones who did not restart therapy.
Patients on soliris had their kidney function rapidly improve and remain stable for up to six years. Treatment discontinuation correlated with a tendency to decrease renal function over time. “Overall, patients who discontinue eculizumab may be at risk for additional TMA manifestations and renal function decreases,” the authors wrote.
Off-treatment blood clot formation rates were higher in those who were children/adolescents at diagnosis, who had identified immune-system-related genetic/autoimmune abnormalities, or had a history of several blood clot events before starting treatment. That suggests these might be risk factors for the occurrence of TMA events while off treatment.
Importantly, the therapy was well-tolerated, and its safety profile was consistent with previous research. Four patients developed meningococcal infections, which were all resolved with appropriate treatment. Of those, three were found to be definitely related to taking Soliris.
“The current study confirms the efficacy and safety of eculizumab in aHUS, particularly with regard to long-term renal function and TMA events,” researchers said.
“Discontinuation of eculizumab, with careful monitoring, is an option in select patients with consideration of patient preference, organ function normalization, and risk factors for relapse, including mutational analysis, age of onset, and history of multiple TMA episodes,” they concluded.