Eosinophilic complications during dupilumab therapy for type 2 diseases: a systematic review

Background: Dupilumab shows promising results in the management of several type 2 disorders. However, it often leads to transient, early increases in blood eosinophil count (BEC). This has led to awareness of possibly associated eosinophilic complications, such as eosinophilic granulomatosis with polyangiitis (EGPA) and hypereosinophilic syndrome (HES). Aim of the current work was to collect all eosinophilic complications reported in literature. Methodology: PubMed, Embase, Scopus, and Web of Science were systematically searched for papers reporting on eosinophilic complications of dupilumab therapy for type 2 disorders. Results: While around one million patients are treated with dupilumab globally, we identified a total of 35 reports on 53 patients. The most common complications were EGPA: 24 patients, eosinophilic pneumonia: 15, and HES: 6. Complications developed after a median of 9 (range: 0-71) weeks and the median eosinophilic count at the moment of diagnosis was 6.38x109 cells/L (IQR 3.13-9.08). Most complications were treated with systemic corticosteroids. Of all patients, 89% discontinued dupilumab therapy and no deceased patients were reported. Conclusions: Reported eosinophilic complications during dupilumab therapy are extremely rare and mostly develop during the first months of treatment, challenging the need for (prolonged) BEC monitoring during dupilumab therapy. No patient patterns or predictors were identified.