Dupilumab treatment is not associated with changes in lymphoma risk in atopic dermatitis and other type 2 inflammatory diseases: data from a large-scale retrospective cohort study

Background: The association between atopic dermatitis (AD) and lymphoma risk remains inconclusive. Dupilumab, approved for moderate-to-severe AD, has been linked to an increased lymphoma risk, raising significant concerns. Objectives: The objective of the study was to clarify the association between AD and lymphoma risk and extend to non-dermatological type 2 inflammatory diseases (T2IDs). This study also aimed to assess the impact of dupilumab on lymphoma risk in AD and non-dermatological T2IDs. Methods: A retrospective cohort study was conducted using the TriNetX database. Propensity-score matching allowed for better comparability, and sensitivity analyses ensured robustness. Results: Among 801,508 cases and controls, AD was associated with an increased risk of lymphoma, e.g., cutaneous T-cell lymphoma (CTCL) and non-Hodgkin lymphoma (NHL). Among 14.4 million cases and controls, non-dermatological T2IDs also conferred an increased lymphoma risk. In the comparison of AD patients treated with dupilumab versus other systemic treatments (n = 7,840 per group), dupilumab exposure did not alter the risk for lymphomas but tended toward reduced risks. This decreased risk association was most evident in non-dermatological T2IDs (n = 16,908 per group). Limitations: Retrospective data analysis, data quality, possible false registration of ICD-10-codes. Conclusion: T2IDs, including AD, are associated with a significantly increased risk for lymphoma. Treatment with dupilumab partially ameliorates this risk association, especially for NHL.