Long-term Nucala for EGPA eases disease activity, improves survival
Real-world data: Treatment may also reduce required glucocorticoid dose
The long-term use of Nucala (mepolizumab) reduces disease activity and the need for standard glucocorticoids, while improving survival, in people with eosinophilic granulomatosis with polyangiitis (EGPA), the rarest type of ANCA-associated vasculitis (AAV).
These are the findings of a real-world study in Japan that compared outcomes between 37 Nucala-treated EGPA patients and 37 matched patients who weren’t given the therapy.
“[Nucala] may control disease activity and reduce the required [glucocorticoid] doses, potentially improving the long-term prognosis in patients with EGPA,” the researchers wrote. While glucocorticoids are a standard anti-inflammatory treatment in AAV, their long-term use at a high dosage is associated with severe side effects.
The study, “Long-term efficacy of mepolizumab in patients with eosinophilic granulomatosis with polyangiitis: a propensity score matching analysis in the multicenter REVEAL cohort study,” was published in Frontiers of Immunology.
EGPA is the most rare type of AAV, a group of autoimmune diseases wherein the immune system mistakenly attacks small blood vessels throughout the body, causing inflammation that damages tissues and organs and leading to a wide range of symptoms. In EGPA, high levels of a type of immune cell called eosinophils in the blood and tissues result in the formation of granulomas, or immune cell clusters. Symptoms primarily impact lung and gastrointestinal tract function, with many people having asthma-like symptoms before being diagnosed.
GlaxoSmithKline’s Nucala is approved as an add-on therapy for certain EGPA patients in several regions, including the U.S. and European Union. The therapy reduces eosinophil levels by blocking IL-5, a small molecule involved in their growth, maturation, and survival, as well as the cells’ movement throughout the body. The approvals were based on data from the international Phase 3 MIRRA clinical trial (NCT02020889) that included 136 adults with relapsing, or treatment-resistant, EGPA.
When patients received Nucala injections under the skin for a year along with standard AAV treatment — glucocorticoids with or without immunosuppressants — they were more likely to achieve disease remission and stay in remission relative to those given a placebo.
The clinical characteristics of MIRRA participants differed from those of patients in real-world clinical settings, and those with organ- or life-threatening manifestations were excluded from the trial, making for “an urgent need to evaluate the effectiveness of [Nucala] in real-world clinical settings,” the researchers wrote.
Real-world outcomes with Nucala
Researchers in Japan compared real-world outcomes between 37 EGPA patients treated with Nucala and 37 patients matched for several demographic and clinical features, but didn’t receive the therapy. All were part of the Registry of Vasculitis Patients to Establish the REAL-WORLD Evidence (REVEAL), an observational study of people with vasculitis, or blood vessel inflammation, in a specific region of Japan.
In both groups, 32 patients had newly diagnosed EGPA, while five had relapsing disease.
The patients’ median age was 60, half were women, and were living with the disease for a median of 84 months, or about seven years. More than a third (38%) tested positive for ANCAs, the self-reactive antibodies that cause most cases of AAV but are less frequently detected in EGPA.
Nucala was given at a dose of 300 mg, once every four weeks. The median duration from Nucala’s administration to the last observation was 26 months, or about two years. The median Birmingham Vasculitis Activity Score (BVAS), a measure of disease activity, at the last observation was 0 for both the Nucala-treated and untreated groups, results showed.
However, more untreated patients exhibited higher BVAS at the last observation relative to Nucala-treated patients, resulting in a significantly higher BVAS in the non-Nucala group.
“These data suggest that [Nucala] can effectively control disease activity even when it is introduced several years after diagnosis,” the researchers wrote.
At the last observation, Nucala was also associated with a significantly lower glucocorticoid dose (median, 4 vs. 5 mg/day) and a significantly greater proportion of patients who achieved a daily glucocorticoid dose of up to 4 mg (51.4% vs. 24.2%). Still, the proportion of patients who became free from glucocorticoids was comparable between the Nucala group (10.8%) and the untreated group (9.1%).
Statistical models adjusted for potential influencing factors showed Nucala treatment was significantly associated with a higher chance of achieving a daily glucocorticoid dose of 4 mg or lower. Having asthma at disease onset was significantly linked to a lower chance of achieving such lower doses, however.
While the MIRRA trial showed Nucala reduced relapses in a subset of EGPA patients, no significant differences were observed between the two groups regarding relapses. This may be due to the higher rate of ANCA positivity in the real-world study compared with the MIRRA study (38% vs. 19%), which may “have made it more challenging to suppress relapses with [Nucala],” the researchers wrote.
A significantly greater proportion of patients given Nucala were alive at five years relative to those not given the therapy (100% vs. 81.3%). Nucala’s superiority in terms of survival was seen regardless of age, year of disease onset, or disease activity measures.
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