Top Research in ANCA-Associated Vasculitis Presented at ACR Convergence 2023

10. Dupilumab for Relapsing or Refractory EGPA

Abstract 0856: Molina et al.¹⁶

The cytokines IL-4 and IL-13 are responsible for mediating the allergic response in a wide range of diseases. IL-4 influences Th2 cell development and antigen-specific IgE responses. IL-13 induces IgE secretion from activated B cells. Dupilumab is a humanized monoclonal antibody that inhibits both IL-4 and IL-13 signaling by binding the IL-4 receptor alpha chain. Dupilumab has been approved by the FDA for the treatment of atopic dermatitis, asthma, eosinophilic esophagitis and prurigo nodularis.

This retrospective study included 50 patients with EGPA who were treated with dupilumab, most commonly for debilitating otolaryngologic manifestations, glucocorticoid dependency or poorly controlled asthma. Of the 50 patients in this study, 33 (66%) had a complete or partial response to dupilumab, which was associated with a reduction in the average daily dose of prednisone from 7 mg to 2.5 mg at 12 months.

Dupilumab-induced eosinophilia was reported in 33 patients (66%), but remained asymptomatic in 42% of cases. Disease flare was reported in 15 patients (30%) and occurred in association with blood eosinophilia in 87% of cases. Most adverse events were mild to moderate (including headache, injection site reactions, myalgias and arthralgias), but two patients experienced non-fatal anaphylactic shock.

Clinically, dupilumab is effective for eosinophilic chronic rhinosinusitis and nasal polyposis, which can be particularly problematic for patients with EGPA. However, clinicians have tended to avoid dupilumab in patients with EGPA due to a concern that dupilumab-induced hypereosinophilia could precipitate a disease flare. This study confirms both trains of thought: Dupiliumab may be an effective therapy for EGPA, but patients need to be monitored carefully for disease flare.

Dupilumab-induced hypereosinophilia tends to dissipate with time, and it will be interesting to see if future studies demonstrate that the associated risk of disease flare dissipates with prolonged therapy. Alternatively, simultaneous treatment with an IL-5 inhibitor may mitigate the risks associated with this drug for patients with underlying hypereosinophilic syndromes.

Philip Seo, MD, MHS, is an associate professor of medicine at Johns Hopkins University School of Medicine. He served as the third physician editor of The Rheumatologist.

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