Dupilumab-Associated Severe Headaches in Chronic Rhinosinusitis With Nasal Polyposis (CRSwNP): A Report of Two Cases With Resolution After Cessation

Dupilumab is a monoclonal antibody that targets interleukin (IL)-4 and IL-13, approved for the treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP). While common adverse effects such as conjunctivitis and injection-site reactions are well characterized, headaches reported in clinical trials are typically described as mild, non-specific, and rarely treatment-limiting. We describe two patients with CRSwNP who developed severe, recurrent headaches shortly after initiating dupilumab therapy. In one case, symptoms improved after discontinuation and recurred upon rechallenge; in the other, the headaches resolved after discontinuation. These observations raise the possibility that dupilumab-associated headaches may occasionally be more severe than previously appreciated. Clinicians should be aware of this potential association when evaluating new-onset headaches in patients receiving dupilumab.