Hypereosinophilia with systemic manifestations under dupilumab and possibility of dual benralizumab and dupilumab therapy in patients with asthma and CRSwNP

Title Symptomatic hypereosinophilia under dupilumab and possibility of dual anti-IL4R and anti-IL5(R)-treatment Background Dupilumab, a monoclonal IL4-receptor antibody, is licensed for severe asthma, refractory CRSwNP and moderate-severe atopic dermatitis. Safety and tolerability profile is favorable and moderate increases in blood eosinophils reported from licensing trials have been moderate and transient. However, symptomatic hypereosinophilia under dupilumab has occasionally been reported since marketing of the drug. Objective To alert clinicians about the possible risk of symptomatic hypereosinophilia under dupilumab treatment and present a possible solution to this problem, consisting of combining anti-IL4R and anti-IL5(R)-treatments. Results In two of our patients symptomatic hypereosinophilia with debilitating cough and eosinophilic pulmonary infiltrates occurred shortly after initiating dupilumab therapy for severe asthma. Prednisolone treatment and switch to anti-IL5R rapidly improved symptoms and eosinophilic count. In addition to severe asthma, one of the patients had severe CRSwNP symptoms that were improved under dupilumab monotherapy, but not controlled under anti-IL5R monotherapy. With a history of three prior nasal polyp operations, ENT surgeons opted against another operation. As dupilumab monotherapy was not tolerated due to hypereosinophilia, dual treatment with dupilumab 300 mg every 2 weeks and benralizumab 30 mg every 8 weeks was given with at least 1-week interval between the 2 drugs. Dual therapy lead to marked symptom improvement both of asthma and CRSwNP and was effective and well tolerated in a 1,5 year follow-up. Conclusion Symptomatic hypereosinophilia may occur during dupilumab treatment for severe asthma. Dual therapy with benralizumab and dupilumab may be effective and well tolerated. Clinical trials should further explore combined therapies for the most severe patients in whom one biologic is not enough to control both upper and lower airway manifestations or who have hypereosinophilic complications under dupilumab. Publication History Article published online: 11 May 2022 © 2022. Thieme. All rights reserved. Georg Thieme Verlag Rüdigerstraße 14, 70469 Stuttgart, Germany