BACKGROUND: It has long been appreciated that multiple allergic/atopic conditions (type-2-inflammation-associated diseases, T2IDs) often appear in the same individual, suggesting a shared systemic immune deviation. Emerging molecular and clinical investigations of interleukin (IL)4/IL13 blockade with the fully-human antibody dupilumab suggest that many are driven by over-activation of the IL4/IL13 pathway, manifesting differently in distinct tissues. METHODS AND RESULTS: We performed comprehensive quantitative analyses using several large, independent datasets (including real-world and clinical trial datasets) to confirm that many T2IDs-including asthma, atopic dermatitis, eosinophilic esophagitis, nasal polyps, prurigo nodularis-are highly interrelated based on co-prevalence, genetic predispositions, and transcriptomic signatures driven by over-activation of the IL4/IL13 pathway. We also summarize extensive clinical trial data showing that these T2IDs also share uniformly impressive clinical responses to dual IL4/IL13 blockade with dupilumab. CONCLUSIONS: While highly consistent with previous data and observations, this is the first systematic comparison of these types of data across multiple T2IDs, using a rigorous quantitative assessment of the largest datasets evaluated to date. Many T2IDs are not only highly interrelated and comorbid, but share transcriptomic signatures and genetic predispositions that suggest they all share over-activation of the IL4/IL13 pathway as a key causative driver, consistent with and explaining their uniform clinical responsiveness to dual IL4/IL13 blockade. These genetic and transcriptomic signatures may also have utility for identifying other diseases mediated by IL4/IL13 or T2-mediated subpopulations of heterogenous inflammatory diseases.
Hamilton et al. (2026) studied this question.