Dual biologic therapy with mepolizumab a novel solution to dupilumab-induced conjunctivitis

Abstract

Introduction: Dupilumab is an interleukin-4 (IL-4) receptor alpha antagonist antibody used to treat severe eosinophilic asthma (SEA) and atopic dermatitis (AD). Mepolizumab is an IL-5 antagonist antibody also used to treat SEA. Adverse effects associated with dupilumab include an elevation in peripheral blood eosinophils and severe conjunctivitis, the mechanism of which is unknown. Current medical management of dupilumab-induced conjunctivitis is topical steroids or cessation of therapy. Case description: A 28-year-old male with established severe AD and SEA refractory to standard medical therapy was started on dupilumab for his AD with significant clinical improvements; his SEA clinically improved but he remained symptomatic. Within four weeks he developed severe bilateral conjunctivitis and his peripheral blood eosinophil count rose from 0 to 5.5 10 E9/L. Mepolizumab was initiated in addition to dupilumab. Three days after his first injection his peripheral eosinophil count dropped to zero, the conjunctivitis resolved, and there was marked improvement in his Asthma Control Questionnaire score. The patient remains on combination therapy, and has had no asthma exacerbations. Case implications: Blocking three T2 cytokine pathways (IL-4, 5 and 13) by administration of concurrent mepolizumab and dupilumab can alleviate dupilumab-associated conjunctivitis and provide additive improvement in asthma control. This case study postulates that the conjunctivitis is associated with disarrangement of the T2 inflammatory pathway. More data is needed on the indications, efficacy and safety of combination biologic therapy in severe asthma; in the interim case reports provide valuable information.