Eosinophilic Organ Complications Associated with Dupilumab Therapy – Narrative Review and Current Evidence

Philipp Suter,1,2,* Vanessa Alexandra Buetler,1,2,* Nina Graf,1,3 Nikolay Pavlov1 1Department of Pneumology, Allergology and Clinical Immunology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland; 2Division of Pulmonology, Department of Medicine and Specialties, Fribourg Hospital and University of Fribourg, Fribourg, Switzerland; 3Division of Pneumology, Department of Internal Medicine, Cantonal Hospital of Grisons, Chur, Switzerland*These authors contributed equally to this workCorrespondence: Philipp Suter, Division of Pulmonology, Department of Medicine and Specialties, Fribourg Hospital and University of Fribourg, Chemin des Pensionnats 2-6, Fribourg, 1708, Switzerland, Tel +41 78 892 14 95, Email [email protected]: Dupilumab is a monoclonal antibody targeting the interleukin (IL) 4 receptor alpha subunit. By inhibiting IL-4 and IL-13 signaling, it has shown efficacy in treating type 2 high inflammatory diseases. While generally well-tolerated, rare eosinophilic adverse events have been reported.Methods: A narrative literature search was conducted using MEDLINE, Google Scholar, and Cochrane Central Register of Controlled Trials databases up to September 6, 2025. We searched for published cases of dupilumab-induced hypereosinophilia with organ involvement. Furthermore, we present data from the WHO Global Pharmacovigilance Database, VigiBase, using information component (IC) metrics.Results: A 64-year-old woman with severe asthma, aspirin-exacerbated respiratory disease, and chronic rhinosinusitis with nasal polyposis developed nine months after dupilumab initiation recurrent eosinophilic pleural effusions (EPE), accompanied by peripheral eosinophilia (2520 cells/μL). Symptoms resolved only after dupilumab discontinuation. Our review includes 52 cases of dupilumab-associated eosinophilic adverse events. Most presented within three months of treatment initiation. Eosinophilic pneumonia (EP), eosinophilic granulomatosis with polyangiitis (EGPA) and hypereosinophilic syndrome (HES) were the most frequent reported manifestations. Although most patients recovered with dupilumab withdrawal and oral corticosteroids, clinical outcomes varied, and re-challenge was associated with a high recurrence rate. Analysis of VigiBase revealed significant values for a disproportionate frequency of reports of several eosinophilic adverse events (EGPA: IC025 +3.4; HES: IC025 +2.8; EP: IC025 +2.6, EPE: IC025 +2.2) in association with dupilumab.Conclusion: Clinically significant eosinophilic adverse events during dupilumab therapy, though rare, can occur even after prolonged treatment periods. Long-term vigilance for eosinophil-mediated organ damage is important and for individualized risk-benefit assessments in patients receiving IL-4/IL-13 blockade is needed. Enhanced awareness and further studies are required to better define predictive markers, pathophysiological mechanisms, and management strategies.Keywords: dupilumab, eosinophilic pleural effusion, hypereosinophilia, biologics, asthma, CRSwNP, adverse events