EGPA long-term survival rates improving for many reasons: Study
Analysis from Japan finds Nucala alone doesn't significantly move data
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Although long-term survival for people with eosinophilic granulomatosis with polyangiitis (EGPA) has improved in Japan, the introduction of Nucala (mepolizumab) as a treatment for the disease may not, on its own, have had a significant effect.
That’s according to a real-world study that analyzed data from 87 EGPA patients, 69.1% of whom were on Nucala. While the therapy was administered in hard-to-treat cases, as indicated, it did not significantly affect survival.
Still, “survival in the [Nucala-treated] group was not inferior to that of the untreated group (comprising patients with less severe disease), suggesting a potential beneficial effect of [Nucala] that could not be detected statistically owing to the limited number of events and confounding by indication,” the researchers wrote. Confounding by indication refers to a bias in which the reason for initiating a treatment (the indication) is associated with the patient’s prognosis; in this case, more severe EGPA, rather than the treatment itself, may influence survival.
The findings suggest that “although overall survival in EGPA has improved over time, this improvement cannot be attributed to a single therapeutic agent,” the researchers wrote.
The study, “Improved long-term prognosis of eosinophilic granulomatosis with polyangiitis: retrospective analysis of 87 patients after biologic therapy introduction in Japan,” was published in Scientific Reports.
Easing inflammation
EGPA is a rare type of ANCA-associated vasculitis (AAV), a group of conditions characterized by inflammation and damage of small blood vessels. This type of AAV often features elevated blood levels of immune cells called eosinophils, as well as a form of asthma driven by those cells. EGPA symptoms commonly affect the ears, nose, and throat.
The main treatment for EGPA is corticosteroids, but long-term use of these medications may lead to serious side effects. Some patients also receive additional immunosuppressive medications.
Nucala is an under-the-skin injectable therapy approved for adults with EGPA as an add-on to corticosteroids. It works by blocking a protein that promotes the growth and survival of eosinophils. The medication is expected to lower eosinophil levels and ease EGPA-driving inflammation.
Nucala was approved in Japan in 2018 for adult EGPA patients with an inadequate response to existing therapies.
While data from clinical trials and real-world studies have shown that Nucala can help control symptoms and reduce the risk of relapse and death in the short- to medium-term, its effect on long-term survival remains poorly understood.
“This lack of evidence underscores the need to identify factors associated with long-term prognosis in the current treatment era,” the researchers wrote.
The team retrospectively analyzed data from 87 Japanese adults with EGPA (62.1% women) treated at two hospitals between April 2018 and December 2024.
Patients’ mean age was 61.5. All had asthma, and more than 90% had problems in the sinuses or nerve damage. Nearly half (49.4%) had heart involvement.
The most common initial treatments were high-dose corticosteroids (74.7%) and immunosuppressants (81.6%). At the last examination, patients were on lower corticosteroid doses. Most were also treated with Nucala (69%), and 67.8% received intravenous immunoglobulin (IVIG) until they achieved remission.
IVIG involves the administration of healthy antibodies to counteract the self-reactive antibodies that typically drive AAV.
The mean follow-up from diagnosis was 10 years, with some patient data extending to nearly 34 years. Estimated survival rates were 95% at five years, 91.4% at 10 years, and 85.2% at 20 years. The most common cause of death was lung infection; no patient died due to the disease itself.
Further statistical analyses showed that older age at EGPA onset (particularly 65 and older) and more severe disease at diagnosis, as assessed with the Birmingham Vasculitis Activity Score (BVAS), were independent predictors of lower survival.
Nucala treatment was not associated with a significant difference in long-term survival, with a similar 20-year survival rate to that of those who didn’t receive the add-on therapy (88.3% vs. 92.6%).
However, patients treated with Nucala had a significantly higher relapse rate and were significantly more likely to have received immunosuppressants during the initial treatment phase, as well as IVIG and a higher corticosteroid dose during maintenance treatment.
“These findings suggest that [Nucala] was administered primarily to patients with more frequent relapse or [treatment-resistant] disease, and any potential benefit of mepolizumab in terms of prognosis may not have been detectable owing to confounding by indication and the limited number of events,” the researchers wrote. “The favorable prognosis for EGPA observed in recent years likely reflects the combined effects of advances in comprehensive disease management, including optimized systemic [corticosteroid] use and adjunct therapies such as IVIG, rather than the effect of [Nucala] alone.”
