Soliris helps curb blood clot risk in PNH, but monitoring still needed
Japanese study points to need for monitoring, especially after past clots
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Treatment with Soliris (eculizumab) appears to help reduce the risk of potentially life-threatening thromboembolic events (TEs), complications caused by clots that disrupt circulation, in people with paroxysmal nocturnal hemoglobinuria (PNH), but it does not eliminate that risk, according to a post-marketing surveillance study from Japan.
Researchers found that people with a history of TEs before starting Soliris were more likely to experience new events during treatment. Some TEs occurred alongside signs of ongoing red blood cell destruction, infections, or longer-than-recommended intervals between Soliris doses, suggesting that the disease may not have been fully controlled at the time of those events.
Blood clot-preventing drugs may help
Among TEs with available medication timing data, more events happened when patients were not taking antithrombotic medications — drugs used to help prevent blood clots — than when they were, suggesting these medications may help reduce TE risk.
“[Soliris] helps prevent TEs in PNH,” the researchers wrote. “Concurrent antithrombotic agent[s] use to prevent TEs in PNH is likely clinically useful, especially in patients with a history of TE.”
The study, “Thrombotic Events in Patients With Paroxysmal Nocturnal Haemoglobinuria Using Eculizumab: A Post-Marketing Surveillance Sub-Analysis,” was published in eJHaem.
PNH occurs when a part of the immune system called the complement cascade mistakenly attacks and destroys red blood cells. This process, known as hemolysis, can lead to anemia, fatigue, and other symptoms. One of the most serious complications, historically affecting up to 44% of untreated people with PNH, is thrombosis, or the formation of blood clots that can cause potentially life-threatening TEs.
Several approved therapies, including Soliris, are known as C5 inhibitors because they target the C5 protein, a component of the complement cascade, to prevent red blood cell destruction. The introduction of these treatments has dramatically reduced the risk of TEs and improved outcomes for people with PNH.
However, TEs can still occur despite treatment and may not always be driven solely by PNH itself. Other factors outside of PNH, “such as advanced age and lifestyle-related disease, may contribute to their occurrence,” the researchers wrote. “Understanding the characteristics associated with TEs in patients with PNH is crucial, given their potentially fatal outcomes.”
Study examined clot risk during treatment
In a previous analysis of data from a Japanese government-mandated long-term post-marketing surveillance study, researchers reported that Soliris showed a favorable long-term safety and effectiveness profile in people with PNH. However, that analysis had not looked specifically at how often TEs occurred during treatment.
“Although Asian patients have been reported to have a lower risk of TEs than patients in the United States, these patients should also be monitored closely for TE risk,” the researchers wrote.
Using data from the same surveillance study, the team set out to assess the frequency and characteristics of TEs in 794 people with PNH treated with Soliris in Japan between June 2010 and August 2019. They also explored possible links between TEs and factors such as antithrombotic medications and underlying health conditions.
Participants had a median age of 59, about half were women (49.2%), and 12.1% had previously experienced a TE. They received Soliris for a median of 1,389 days, or about 3.8 years.
During treatment with Soliris, 44 patients (5.5%) experienced 54 TEs. The most common were deep vein thrombosis, which occurs when clots form in deep veins, usually in the legs, and cerebral infarction, a type of stroke caused by blocked blood flow to the brain.
New events were reported more often among people who had experienced a TE before starting Soliris than among those without such a history (11.5% vs. 4.7%). Patients with a previous TE were also more likely to experience multiple TEs during treatment. Age, sex, and a history of bone marrow failure disorders were not linked to TE risk.
Some events followed signs of disease activity
Among patients with available data, nearly two-thirds of events (61.5%) were preceded by elevated levels of lactate dehydrogenase (LDH), a marker of ongoing red blood cell destruction. Some events also occurred alongside infections or after longer-than-recommended intervals between Soliris doses. According to the researchers, these findings suggest PNH may not have been fully controlled when the TE occurred.
Among the 44 patients who experienced TEs, 32 (72.7%) had used antithrombotic medications during Soliris treatment. Among TEs with available medication timing data, more events happened when patients were off these medications than when they were taking them (71.8% vs. 28.2%). These findings suggest that using antithrombotic agents along with Soliris may be of benefit “in managing TE risk regardless of a history of TE,” the team noted.
“The current findings contribute to the growing body of evidence supporting the benefit of … C5 inhibition in reducing thrombotic risk in Japanese patients with PNH,” the researchers wrote. “[Soliris] appears to help prevent TEs in PNH, but it cannot eliminate their occurrence entirely.”
“Concurrent [antithrombotics] use to prevent TEs in PNH is likely clinically useful, especially in patients with a history of TE, but further evaluation is required,” the team added.
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