Nucala benefits EGPA, but response varies by organ involvement
Review of 8 studies found more than half of patients achieved remission
Long-term treatment with Nucala (mepolizumab) is safe and effective in people with eosinophilic granulomatosis with polyangiitis (EGPA), the rarest type of ANCA-associated vasculitis (AAV), according to a meta-analysis of eight studies.
After nearly two years of treatment, more than half of EGPA patients achieved remission, meaning they had no signs of active disease. Daily doses of standard anti-inflammatory corticosteroids dropped significantly, with about 30% of patients being able to discontinue corticosteroids altogether. A similar proportion stopped other immunosuppressive medications.
Patients with heart or nerve involvement, however, experienced less reduction in corticosteroid use compared with those without these complications, “highlighting the need for combination strategies targeting complementary pathways,” researchers wrote.
The findings were published in the European Journal of Allergy and Clinical Immunology as a letter to the editor, titled “Efficacy and Safety of Mepolizumab 300 mg in Eosinophilic Granulomatosis With Polyangiitis: A Meta-Analysis of Eight Retrospective Studies.”
A need for safer, more targeted approaches
AAV refers to a group of conditions marked by inflammation of blood vessels of small and medium size, which can damage multiple organs.
In EGPA, the rarest AAV type, this inflammation is driven by eosinophils, a type of immune cell that accumulates in tissues and forms granulomas, or dense clusters of inflammatory cells. The disease mainly affects the lungs, nerves, and gastrointestinal system, but the heart or kidneys can be involved in some cases.
Standard treatment typically relies on long-term corticosteroids, either alone or combined with other immunosuppressive drugs. While often effective, prolonged corticosteroid use can cause serious side effects, highlighting the need for safer, more targeted approaches.
Nucala, marketed by GlaxoSmithKline (GSK), is approved as an add-on to standard treatment with corticosteroids for certain EGPA patients in the U.S., Canada, Japan, and European Union.
Administered via subcutaneous, or under-the-skin, injections, Nucala targets interleukin-5 (IL-5). This signaling protein promotes the growth, maturation, and survival of eosinophils. By lowering eosinophil levels, the therapy is expected to reduce inflammation and ease symptoms in people with EGPA.
Clinical trials and real-world studies have shown that long-term treatment can safely reduce disease activity and relapse rates, and prolong survival, while reducing corticosteroid use.
“However, therapeutic responses vary widely, underscoring the urgent need for predictive biomarkers to optimize patient selection and treatment strategies,” the researchers wrote.
Nucala More than 30% of patients on Nucala were able to halt corticosteroids
Now, a team of researchers in Italy systematically has reviewed studies published up to October 2024 reporting outcomes of EGPA patients treated with Nucala at the approved 300 mg monthly dose.
A total eight retrospective studies, covering 165 patients, were included in the final analysis. Participants’ mean age ranged from 44.7 to 73.2 years, and they were treated for a mean of 95 weeks, or nearly two years.
More than half of patients (54%) achieved disease remission. Regardless of the specific corticosteroid used, patients were taking, on average, the equivalent of 6.37 mg less prednisone per day after treatment with Nucala.
In addition, 30.4% of patients were able to stop taking corticosteroids, and 30.5% discontinued other immunosuppressive medications.
The treatment was generally well tolerated, with mild to moderate adverse events reported in 19.3% of patients. None discontinued the therapy due to adverse events.
[Nucala] appears to be a promising therapeutic option for EGPA management.
Further statistical analysis found that having nerve damage, known as neuropathy, or heart involvement significantly predicted a weaker reduction in corticosteroid use during treatment. This means patients with these complications were less likely to have their corticosteroid doses reduced as much as patients without these complications.
The researchers suggested these individuals may “constitute a more [treatment-resistant] subgroup with diminished responses to IL-5 blockade.”
Data on lung and kidney involvement were insufficient to draw conclusions.
“In conclusion, [Nucala] appears to be a promising therapeutic option for EGPA management,” the researchers wrote. However, they noted that “the variability in [Nucala] efficacy highlights the complexity of EGPA, necessitating a precision medicine approach. Future research should focus on alternative biologics, combination regimens, and long-term outcomes to further refine EGPA treatment paradigms.”
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