Dupilumab improves comorbid type 2 inflammatory diseases in AD patients
Published Online: March 2021
Atopic dermatitis (AD) is a chronic inflammatory skin disease involving impaired skin barrier function and systemic immune system dysregulation, particularly upregulation of the type 2 immune pathway. Patients with AD often have other conditions that are also characterized by type 2 inflammation, including asthma, allergic rhinitis, other chronic inflammatory sinonasal conditions, and other allergies. These comorbid conditions increase the burden on patients and add to the complexity of disease management. Dupilumab is a human monoclonal antibody that inhibits signaling of cytokines interleukin (IL)-4 and IL-13, which are key and central drivers of type 2 inflammatory diseases. While the efficacy and safety of dupilumab have been separately established in AD, asthma, and chronic rhinosinusitis with nasal polyposis, the benefit in AD patients with concurrent type 2 inflammatory diseases has not been previously evaluated.
In a recent study published in The Journal of Allergy and Clinical Immunology: In Practice, Boguniewicz et al. report an analysis of dupilumab treatment outcomes in AD patients with comorbid asthma and/or sinonasal conditions who were enrolled in four phase 3 randomized clinical trials. In these trials patients received placebo, dupilumab 300 mg every 2 weeks, or dupilumab 300 mg weekly.
This post hoc analysis assessed improvements from baseline to week 16 in asthma using the Asthma Control Questionnaire-5 (ACQ-5) and sinonasal conditions using the Sino-Nasal Outcome Test-22 (SNOT-22) in three subgroups of patients: AD patients with comorbid asthma, AD patients with comorbid sinonasal conditions, and AD patients with both asthma and sinonasal conditions. Improvements in AD signs and symptoms were also assessed in all patients. Among the 2,444 study patients, 83% reported having one or more type 2 inflammatory diseases in addition to AD, including 30% with asthma and 48% with sinonasal conditions (allergic rhinitis, chronic rhinitis or rhinosinusitis, nasal polyps); 13% had both asthma and sinonasal conditions. After 16 weeks, dupilumab treatment resulted in significant improvements overall (least squares mean change from baseline) in ACQ-5 scores (0.59 for dupilumab vs 0.27 for placebo), SNOT-22 scores (9.9 for dupilumab vs 5.1 for placebo), and signs and symptoms of AD, with an acceptable safety profile. Significantly more dupilumab-treated AD patients achieved clinically meaningful improvements in ACQ-5 and SNOT-22 vs placebo. Similar results were achieved in AD patients with both asthma and sinonasal conditions.
This analysis demonstrates that, in adult patients with moderate-to-severe AD and comorbid asthma and/or chronic sinonasal conditions, dupilumab significantly improved all three conditions concurrently. Dupilumab may help optimize treatment management for patients with concurrent AD, asthma, and/or chronic sinonasal conditions by addressing the common systemic immune dysregulation underlying their pathophysiology.
The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.