Dear Editor: We read with great interest the real-world analysis by Anisman et al. examining systemic outcomes associated with dupilumab use in patients with chronic rhinosinusitis with nasal polyps and/or asthma 1. By leveraging a large multinational electronic health record network, the authors extend the discussion of biologic therapy beyond symptom control and into broader morbidity patterns that are highly relevant to long-term patient management. A central contribution of this study lies in its observation of reduced cardiovascular and thromboembolic events among dupilumab-treated patients compared with biologic-naïve cohorts and selected comparator biologics. This signal is particularly noteworthy given the established association between chronic type 2 inflammatory airway diseases and elevated cardiovascular risk. The findings raise the possibility that the sustained suppression of interleukin-4 and interleukin-13 signaling may influence systemic inflammatory and prothrombotic pathways that extend well beyond the sinonasal and bronchial mucosa. From a clinical perspective, this observation encourages reconsideration of biologic therapy as a modifier of multimorbidity rather than solely a controller of airway disease activity. The analytical approach, based on propensity score matching across demographics, comorbidities, medication exposure, and healthcare utilization, strengthens the internal coherence of the comparisons. Importantly, the authors excluded patients with prior events for each outcome, thereby focusing on incident morbidity after treatment initiation. The consistency of cardiovascular risk reduction across multiple endpoints—including myocardial infarction, venous thrombosis, and pulmonary embolism—adds coherence to the observed associations and suggests a biologically plausible pattern rather than isolated findings 2. The increased incidence of eosinophilia observed with dupilumab, juxtaposed against reduced cardiovascular and thromboembolic risk, presents an intriguing paradox. Eosinophils have been implicated in platelet activation and vascular inflammation, yet in this cohort, eosinophilia did not translate into excess downstream vascular events. This dissociation suggests that circulating eosinophil counts alone may be an insufficient surrogate for vascular risk in the context of targeted cytokine inhibition 3. It also invites further mechanistic exploration into qualitative changes in eosinophil function, trafficking, or tissue compartmentalization under interleukin-4/interleukin-13 blockade. The reported reduction in newly coded sleep apnea diagnoses among dupilumab users represents another clinically meaningful extension of benefit. Given the close relationship between nasal obstruction, sleep-disordered breathing, and cardiometabolic risk, this observation aligns with the broader theme that the improved control of upper airway inflammation may yield systemic health dividends. For clinicians, this finding reinforces the relevance of assessing sleep-related outcomes when evaluating biologic response in patients with combined sinonasal and lower airway disease. Comparative analyses with other biologics further enhance the translational value of the study. The generally more favorable cardiovascular and musculoskeletal profile relative to omalizumab and mepolizumab, alongside similarity to tezepelumab, supports the concept that the upstream modulation of type 2 inflammation may have distinct systemic consequences depending on the targeted node within the inflammatory cascade. These nuances are particularly relevant as therapeutic choices increasingly involve multiple biologic options with overlapping indications. In conclusion, this large-scale real-world analysis suggests that dupilumab use in Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) and asthma may be associated with reductions in cardiovascular, thromboembolic, and sleep-related morbidity that extend beyond airway symptom improvement. These observations provide a compelling rationale for future prospective and mechanistic studies to determine whether such associations reflect true disease-modifying effects and to define their implications for long-term risk stratification and personalized biologic selection in type 2 inflammatory airway disease. Kotina Shridevi: Validation, writing – original draft, writing – review & editing. Megha Doiphode: Supervision, project administration, writing – original draft, writing – review & editing. Rakhi Mishra: Conceptualization, methodology, writing – original draft, writing – review & editing. Archana Dhyani: Writing – original draft, writing – review & editing. During the preparation of this work, the authors used Grammarly and ChatGPT in order to refine language, grammar, and style. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication. All authors reviewed and approved the manuscript. No funding was received for this study. The authors declare no conflicts of interest. The authors have nothing to report.
Shridevi et al. (Sat,) studied this question.