Mepolizumab Likely Efficacious in Patients With EGPA

Mepolizumab is clinically effective in patients with eosinophilic granulomatosis with polyangiitis (EGPA), a form of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), with or without a vasculitis phenotype, according to a study published in ACR Open Rheumatology.

Among the therapies typically administered to patients with EGPA are immunosuppressants and cytotoxic agents, which can result in significant toxicity. In addition, these therapies do not exclude the occurrences of relapses, which can be common despite strict treatment adherence.

Mepolizumab is a humanized monoclonal antibody that works by binding to and inactivating interleukin-5, thus decreasing the amount of eosinophils within the blood and tissue. Because EGPA with or without a vasculitic phenotype is driven by eosinophils, eosinophil-targeting agents such as mepolizumab may hold therapeutic potential.

The phase 3 MIRRA study found that patients with EGPA of either vasculitic phenotype on mepolizumab therapy experienced a longer period of disease remission and had reduced oral glucocorticoid usage compared with placebo. However, this study did not separate its findings based on specific EGPA phenotypes. Terrier and colleagues thus set out to investigate the merits of mepolizumab based on vasculitic phenotype.

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The researchers conducted a post hoc analysis using data from the MIRRA study, investigating the efficacy of mepolizumab in controlling symptoms and inducing remission in patients with or without a vasculitic EGPA phenotype. They assessed accrued remission over 52 weeks and the proportion of patients in remission at weeks 36 and 48. Remission was defined as achieving a Birmingham Vasculitis Activity Score of 0 and being on an oral glucocorticoid dose 4 mg/day or higher of a prednisolone equivalent.

One hundred thirty-six patients were randomized to treatment in the MIRRA study. Terrier and colleagues reported that, based on the endpoints used in this study, mepolizumab was more effective than placebo on all counts in patients with or without a vasculitic EGPA phenotype. Mepolizumab reduces all types of relapses at any point of the treatment period for all patients with EGPA.

“These results suggest patients with EGPA and a vasculitic phenotype are likely to achieve clinical benefits with mepolizumab, thus providing valuable information for clinicians treating patients with EGPA with and without vasculitic phenotypes,” the authors concluded.